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RJR: Recommended Bibliography 21 Feb 2026 at 02:02 Created:
Telomeres
Wikipedia: A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos (τέλος) "end" and merοs (μέρος, root: μερ-) "part". For vertebrates, the sequence of nucleotides in telomeres is TTAGGG, with the complementary DNA strand being AATCCC, with a single-stranded TTAGGG overhang. This sequence of TTAGGG is repeated approximately 2,500 times in humans. In humans, average telomere length declines from about 11 kilobases at birth to less than 4 kilobases in old age,[3] with average rate of decline being greater in men than in women. During chromosome replication, the enzymes that duplicate DNA cannot continue their duplication all the way to the end of a chromosome, so in each duplication the end of the chromosome is shortened (this is because the synthesis of Okazaki fragments requires RNA primers attaching ahead on the lagging strand). The telomeres are disposable buffers at the ends of chromosomes which are truncated during cell division; their presence protects the genes before them on the chromosome from being truncated instead. The telomeres themselves are protected by a complex of shelterin proteins, as well as by the RNA that telomeric DNA encodes.
Created with PubMed® Query: telomere.q.txt NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2026-02-20
Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort.
Molecular medicine (Cambridge, Mass.) pii:10.1186/s10020-026-01423-6 [Epub ahead of print].
Additional Links: PMID-41721457
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PubMed:
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@article {pmid41721457,
year = {2026},
author = {Gil-Korilis, A and Ergui-Arbizu, J and Hanák, P and Danešová, N and Tomášová, K and Valíčková, A and Horák, J and Gentiluomo, M and Levý, M and Křivonosková, S and Král, J and Jungwirth, J and Vodičková, L and Vymetálková, V and Azqueta, A and Campa, D and Vodička, P and Vodenková, S},
title = {Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10020-026-01423-6},
pmid = {41721457},
issn = {1528-3658},
support = {LX22NPO5102//National Institute for Cancer Research/ ; NU22J-03-00033//Ministry of Health of the Czech Republic in cooperation with the Czech Health Research Council/ ; GX21-04607X//Grantová Agentura České Republiky/ ; G22-05942S//Grantová Agentura České Republiky/ ; 540225//Charles University Czech Republic/ ; },
}
RevDate: 2026-02-20
Near telomere-to-telomere genome assembly of the stone loach (Traccatichthys pulcher).
Scientific data pii:10.1038/s41597-026-06849-5 [Epub ahead of print].
Traccatichthys pulcher is an ornamental loach species recognized for its vibrant body coloration, characteristic black dorsal fin margin, and iridescent green lateral stripes. To advance genomic research on this species, a high-quality, near telomere-to-telomere (T2T) genome assembly was generated using PacBio HiFi, ONT ultra-long, and Hi-C sequencing technologies. The resulting haplotype-resolved assembly spanned approximately 623.68 Mb, with a contig N50 of 22.9 Mb, and was anchored onto 24 chromosomes. Telomeric sequences were detected at both ends of eight chromosomes and at one end of 13 chromosomes. Twenty-three chromosomes were entirely gapless, while a single gap was identified in the remaining chromosome. The assembly contained 119.1 Mb of repetitive elements, and 23 967 protein-coding genes were annotated. BUSCO analysis indicated high completeness, with 98.6% of conserved genes recovered. This high-quality, near T2T genome assembly offers a valuable and robust genetic resource for investigating molecular mechanisms, evolutionary processes, conservation biology, and selective breeding of T. pulcher.
Additional Links: PMID-41720809
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PubMed:
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@article {pmid41720809,
year = {2026},
author = {Du, LN and Wang, ZC and Chen, ZN and Qin, ZX and Li, CH},
title = {Near telomere-to-telomere genome assembly of the stone loach (Traccatichthys pulcher).},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06849-5},
pmid = {41720809},
issn = {2052-4463},
abstract = {Traccatichthys pulcher is an ornamental loach species recognized for its vibrant body coloration, characteristic black dorsal fin margin, and iridescent green lateral stripes. To advance genomic research on this species, a high-quality, near telomere-to-telomere (T2T) genome assembly was generated using PacBio HiFi, ONT ultra-long, and Hi-C sequencing technologies. The resulting haplotype-resolved assembly spanned approximately 623.68 Mb, with a contig N50 of 22.9 Mb, and was anchored onto 24 chromosomes. Telomeric sequences were detected at both ends of eight chromosomes and at one end of 13 chromosomes. Twenty-three chromosomes were entirely gapless, while a single gap was identified in the remaining chromosome. The assembly contained 119.1 Mb of repetitive elements, and 23 967 protein-coding genes were annotated. BUSCO analysis indicated high completeness, with 98.6% of conserved genes recovered. This high-quality, near T2T genome assembly offers a valuable and robust genetic resource for investigating molecular mechanisms, evolutionary processes, conservation biology, and selective breeding of T. pulcher.},
}
RevDate: 2026-02-20
Telomere recapping via gene therapy as a beneficial strategy for cardio-renal syndrome type 4.
Kidney international pii:S0085-2538(26)00130-4 [Epub ahead of print].
INTRODUCTION: Cardio-renal syndrome type 4 (CRS4) is defined as heart failure driven by chronic kidney disease (CKD). Cardiovascular mortality is the leading cause of death in patients with advanced CKD with current medical treatments exhibiting limited efficacy. Short leukocyte telomere lengths in such patients are correlated with increased mortality, particularly cardiovascular mortality. Here, we examined telomere shortening in mouse and human cardiomyocyte models of CRS4 and its potential protective role by overexpression of telomerase reverse transcriptase.
METHODS: We engineered an adeno-associated virus9 (AAV9) gene therapy JV101, which overexpressed catalytically inactive and nuclear localized human telomerase reverse transcriptase (modhTERT) under cardiac troponin T promotor control. Both in vivo and in vitro models were utilized to conduct a comprehensive evaluation of the therapeutic effects of modhTERT on CRS4.
RESULTS: Overexpression of modhTERT recapped myocardial telomeres, and reversed cardiac dysfunction, hypertrophy and fibrosis, and mitochondrial dysfunction in two CRS4 mouse models: 5/6 nephrectomy and Angiotensin II - high salt - uninephrectomy. The reversal of cardiac dysfunction by modhTERT was both long-term and persistent. In contrast, beta-blocker administration merely delayed the progression of heart failure in these models, without achieving functional reversal. Surprisingly, JV101 ameliorated kidney function as measured by blood urea nitrogen levels in CKD murine models. Experiments in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) demonstrated that modhTERT bound to myocardial telomeric ends. Transcriptomic analysis of isolated mouse cardiomyocytes revealed that modhTERT reversed differentially repressed genes that were highly enriched in mitochondrial metabolism. Coculture of hiPSC-CMs with serum from hemodialysis patients or indoxyl sulfate toxin induced myocardial contractile dysfunction. Overexpression of modhTERT also blocked further telomere shortening and reversed contractile dysfunction in hiPSC-CMs.
CONCLUSION: Our results provide proof-of-concept evidence for treating CRS4 by telomere recapping gene therapy.
Additional Links: PMID-41720267
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PubMed:
Citation:
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@article {pmid41720267,
year = {2026},
author = {Xie, D and Wang, C and Wan, X and Wang, L and Zhao, Y and Pan, J and Zhao, Y and Ji, J and Li, J and Liu, Y and Ding, F and Chang, ACY and Ding, W},
title = {Telomere recapping via gene therapy as a beneficial strategy for cardio-renal syndrome type 4.},
journal = {Kidney international},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.kint.2026.01.022},
pmid = {41720267},
issn = {1523-1755},
abstract = {INTRODUCTION: Cardio-renal syndrome type 4 (CRS4) is defined as heart failure driven by chronic kidney disease (CKD). Cardiovascular mortality is the leading cause of death in patients with advanced CKD with current medical treatments exhibiting limited efficacy. Short leukocyte telomere lengths in such patients are correlated with increased mortality, particularly cardiovascular mortality. Here, we examined telomere shortening in mouse and human cardiomyocyte models of CRS4 and its potential protective role by overexpression of telomerase reverse transcriptase.
METHODS: We engineered an adeno-associated virus9 (AAV9) gene therapy JV101, which overexpressed catalytically inactive and nuclear localized human telomerase reverse transcriptase (modhTERT) under cardiac troponin T promotor control. Both in vivo and in vitro models were utilized to conduct a comprehensive evaluation of the therapeutic effects of modhTERT on CRS4.
RESULTS: Overexpression of modhTERT recapped myocardial telomeres, and reversed cardiac dysfunction, hypertrophy and fibrosis, and mitochondrial dysfunction in two CRS4 mouse models: 5/6 nephrectomy and Angiotensin II - high salt - uninephrectomy. The reversal of cardiac dysfunction by modhTERT was both long-term and persistent. In contrast, beta-blocker administration merely delayed the progression of heart failure in these models, without achieving functional reversal. Surprisingly, JV101 ameliorated kidney function as measured by blood urea nitrogen levels in CKD murine models. Experiments in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) demonstrated that modhTERT bound to myocardial telomeric ends. Transcriptomic analysis of isolated mouse cardiomyocytes revealed that modhTERT reversed differentially repressed genes that were highly enriched in mitochondrial metabolism. Coculture of hiPSC-CMs with serum from hemodialysis patients or indoxyl sulfate toxin induced myocardial contractile dysfunction. Overexpression of modhTERT also blocked further telomere shortening and reversed contractile dysfunction in hiPSC-CMs.
CONCLUSION: Our results provide proof-of-concept evidence for treating CRS4 by telomere recapping gene therapy.},
}
RevDate: 2026-02-20
CmpDate: 2026-02-20
Improved Step-by-Step qPCR Method for Absolute Telomere Length Measurement.
Methods and protocols, 9(1): pii:mps9010022.
Telomere length is a crucial marker of cellular aging and genomic stability, with significant implications for age-related diseases and cancers. This study introduces an improved quantitative PCR (qPCR) method for measuring absolute telomere length, addressing the need for accurate and high-throughput assessment in both clinical and research settings. Novel primers were designed for the single-copy gene interferon beta (IFNB1) to serve as an internal control, alongside a series of single-stranded oligonucleotide standards to establish a calibration curve. This approach allows for precise quantification of telomere length in kilobases per single copy gene copy number per chromosome. We validated this method using DNA samples from peripheral blood and buccal swabs from 17 healthy human volunteers, as well as umbilical cord blood from 9 healthy newborn babies, demonstrating its high linearity and reproducibility. Our findings indicate that this improved qPCR technique provides a rapid, cost-effective, and accurate means of measuring absolute telomere length, thereby facilitating large-scale studies and enhancing clinical diagnostics related to telomere biology.
Additional Links: PMID-41718324
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PubMed:
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@article {pmid41718324,
year = {2026},
author = {Arshinova, ES and Karpova, NS and Terekhina, OL and Nurbekov, M and Burtovskaya, MI},
title = {Improved Step-by-Step qPCR Method for Absolute Telomere Length Measurement.},
journal = {Methods and protocols},
volume = {9},
number = {1},
pages = {},
doi = {10.3390/mps9010022},
pmid = {41718324},
issn = {2409-9279},
support = {FGFU-2025-0007//Federal State Budgetary Institution the "Research Institute of Pathology and Pathophysiology/ ; },
abstract = {Telomere length is a crucial marker of cellular aging and genomic stability, with significant implications for age-related diseases and cancers. This study introduces an improved quantitative PCR (qPCR) method for measuring absolute telomere length, addressing the need for accurate and high-throughput assessment in both clinical and research settings. Novel primers were designed for the single-copy gene interferon beta (IFNB1) to serve as an internal control, alongside a series of single-stranded oligonucleotide standards to establish a calibration curve. This approach allows for precise quantification of telomere length in kilobases per single copy gene copy number per chromosome. We validated this method using DNA samples from peripheral blood and buccal swabs from 17 healthy human volunteers, as well as umbilical cord blood from 9 healthy newborn babies, demonstrating its high linearity and reproducibility. Our findings indicate that this improved qPCR technique provides a rapid, cost-effective, and accurate means of measuring absolute telomere length, thereby facilitating large-scale studies and enhancing clinical diagnostics related to telomere biology.},
}
RevDate: 2026-02-19
Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.
Cell reports, 45(3):117004 pii:S2211-1247(26)00082-3 [Epub ahead of print].
The alternative lengthening of telomeres (ALT) pathway is a recombination-based telomere maintenance mechanism used by a subset of human cancers and is characterized by telomere clustering within telomere-associated promyelocytic leukemia (PML) nuclear bodies (APBs). Although ALT telomeres exhibit reduced nucleosome density, they are paradoxically enriched for heterochromatin-associated factors, raising questions about how chromatin state contributes to ALT. Here, we use a targeted system to locally modulate heterochromatin features at telomeres. We show that telomeric heterochromatin promotes telomere clustering and multiple hallmarks of APB-associated telomere processing in ALT-positive (ALT+) cells. Remarkably, molecular tethering of HP1α at telomeres is sufficient to nucleate PML nuclear bodies in non-ALT cells and, in specific contexts, induce biomarkers of ALT-like recombination. We further demonstrate that heterochromatin-driven PML-telomere colocalization is inhibited by α-thalassemia/mental retardation, X-linked and death domain-associated protein (ATRX/DAXX), factors frequently mutated in ALT+ tumors. Together, these findings establish telomeric heterochromatin as a driver of telomere clustering and PML nuclear body assembly, shaping ALT-associated subnuclear compartmentalization.
Additional Links: PMID-41712379
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PubMed:
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@article {pmid41712379,
year = {2026},
author = {Taylor, ER and Proctor, B and Vaurs, M and Wu, G and Mahieu, M and Shrestha, S and Morrison, D and Weatherly, L and Brelinsky, S and Raghunandan, M and Decottignies, A and Arnoult, N},
title = {Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.},
journal = {Cell reports},
volume = {45},
number = {3},
pages = {117004},
doi = {10.1016/j.celrep.2026.117004},
pmid = {41712379},
issn = {2211-1247},
abstract = {The alternative lengthening of telomeres (ALT) pathway is a recombination-based telomere maintenance mechanism used by a subset of human cancers and is characterized by telomere clustering within telomere-associated promyelocytic leukemia (PML) nuclear bodies (APBs). Although ALT telomeres exhibit reduced nucleosome density, they are paradoxically enriched for heterochromatin-associated factors, raising questions about how chromatin state contributes to ALT. Here, we use a targeted system to locally modulate heterochromatin features at telomeres. We show that telomeric heterochromatin promotes telomere clustering and multiple hallmarks of APB-associated telomere processing in ALT-positive (ALT+) cells. Remarkably, molecular tethering of HP1α at telomeres is sufficient to nucleate PML nuclear bodies in non-ALT cells and, in specific contexts, induce biomarkers of ALT-like recombination. We further demonstrate that heterochromatin-driven PML-telomere colocalization is inhibited by α-thalassemia/mental retardation, X-linked and death domain-associated protein (ATRX/DAXX), factors frequently mutated in ALT+ tumors. Together, these findings establish telomeric heterochromatin as a driver of telomere clustering and PML nuclear body assembly, shaping ALT-associated subnuclear compartmentalization.},
}
RevDate: 2026-02-19
CmpDate: 2026-02-19
Identification of key biomarkers of telomere-related genes in diabetic nephropathy via bioinformatic analysis.
Frontiers in genetics, 17:1566012.
BACKGROUND: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Understanding the molecular mechanisms underlying DN is crucial for developing new therapeutic targets and diagnostic biomarkers.
METHODS: We utilized microarray data from the GEO database to identify differentially expressed genes related to DN. Machine learning algorithms, including LASSO regression and SVM-RFE, were employed to screen and validate telomere-related genes. We also predicted the transcription factors of the significant genes. Subsequently, correlation analysis and Receiver Operating Characteristic diagnostics were performed on the key genes, along with validation using external datasets. Additionally, GSEA enrichment analysis and immune infiltration analysis were conducted. Furthermore, we analyzed the expression of significant genes in cell subgroups using single-cell sequencing technology. Finally, key genes were validated in DN kidney biopsy tissues and normal kidney biopsy tissues.
RESULTS: Through differential analysis and machine learning screening, we identified a total of 14 differentially expressed genes related to telomeres, among which TRIM22, ELOVL4, NLGN4X, and FOSB were highlighted as key genes. We also predicted seven related transcription factors (BCLAF1, HNRNPL, TAF15, STAT1, SRSF9, SAFB2, PTEN). The key gene TRIM22 showed a high correlation with NLGN4X, ELOVL4, and NLGN4X. ROC diagnostics demonstrated sufficient diagnostic accuracy in both the test and validation sets. GSEA enrichment analysis and immune infiltration analysis revealed significant differences among immune cells, such as PC cells, and preliminary expression validation was conducted using single-cell analysis (for example, TRIM22 exhibited high expression levels in EDC, PEC, MES, and IMC). Finally, we performed RT-PCR between DN samples and control samples, finding that the expression levels of key genes in both groups were consistent with the trends predicted by bioinformatics, indicating that these genes may serve as potential diagnostic biomarkers and therapeutic targets.
CONCLUSION: This study provides a comprehensive analysis of telomere-related DEGs in DN, enhancing our understanding of DN pathogenesis. The identified key genes offer potential for new diagnostic and therapeutic strategies, warranting further investigation into their biological roles in DN.
Additional Links: PMID-41709877
PubMed:
Citation:
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@article {pmid41709877,
year = {2026},
author = {Yu, D and Feng, Z and Yao, H and An, K},
title = {Identification of key biomarkers of telomere-related genes in diabetic nephropathy via bioinformatic analysis.},
journal = {Frontiers in genetics},
volume = {17},
number = {},
pages = {1566012},
pmid = {41709877},
issn = {1664-8021},
abstract = {BACKGROUND: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Understanding the molecular mechanisms underlying DN is crucial for developing new therapeutic targets and diagnostic biomarkers.
METHODS: We utilized microarray data from the GEO database to identify differentially expressed genes related to DN. Machine learning algorithms, including LASSO regression and SVM-RFE, were employed to screen and validate telomere-related genes. We also predicted the transcription factors of the significant genes. Subsequently, correlation analysis and Receiver Operating Characteristic diagnostics were performed on the key genes, along with validation using external datasets. Additionally, GSEA enrichment analysis and immune infiltration analysis were conducted. Furthermore, we analyzed the expression of significant genes in cell subgroups using single-cell sequencing technology. Finally, key genes were validated in DN kidney biopsy tissues and normal kidney biopsy tissues.
RESULTS: Through differential analysis and machine learning screening, we identified a total of 14 differentially expressed genes related to telomeres, among which TRIM22, ELOVL4, NLGN4X, and FOSB were highlighted as key genes. We also predicted seven related transcription factors (BCLAF1, HNRNPL, TAF15, STAT1, SRSF9, SAFB2, PTEN). The key gene TRIM22 showed a high correlation with NLGN4X, ELOVL4, and NLGN4X. ROC diagnostics demonstrated sufficient diagnostic accuracy in both the test and validation sets. GSEA enrichment analysis and immune infiltration analysis revealed significant differences among immune cells, such as PC cells, and preliminary expression validation was conducted using single-cell analysis (for example, TRIM22 exhibited high expression levels in EDC, PEC, MES, and IMC). Finally, we performed RT-PCR between DN samples and control samples, finding that the expression levels of key genes in both groups were consistent with the trends predicted by bioinformatics, indicating that these genes may serve as potential diagnostic biomarkers and therapeutic targets.
CONCLUSION: This study provides a comprehensive analysis of telomere-related DEGs in DN, enhancing our understanding of DN pathogenesis. The identified key genes offer potential for new diagnostic and therapeutic strategies, warranting further investigation into their biological roles in DN.},
}
RevDate: 2026-02-18
A tomato telomere-to-telomere super-pangenome empowers stress resilience breeding.
Nature genetics [Epub ahead of print].
Tomato (Solanum lycopersicum), one of the world's most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience.
Additional Links: PMID-41708786
PubMed:
Citation:
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@article {pmid41708786,
year = {2026},
author = {Shi, C and Chen, S and Wang, J and Chen, W and Sun, C and Guo, Q and Liao, S and Wang, H and Mu, Y and Shu, X and Meng, D and Zhao, J and Dong, L and Zhao, L and Hou, S and Guo, L and Yang, C},
title = {A tomato telomere-to-telomere super-pangenome empowers stress resilience breeding.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {41708786},
issn = {1546-1718},
support = {SYS202206//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; ZR2023JQ010//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; },
abstract = {Tomato (Solanum lycopersicum), one of the world's most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience.},
}
RevDate: 2026-02-18
Near telomere-to-telomere genome assembly of Lannea coromandelica provides insights into karyotype evolution in Anacardiaceae.
Additional Links: PMID-41707861
Publisher:
PubMed:
Citation:
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@article {pmid41707861,
year = {2026},
author = {Hou, L and Guo, X and Yang, Z and Zhang, J and Zhang, Y and Liu, Q and Xu, Z and Sun, Y and Liu, Q and Zhang, N and Ma, L and Zhou, G and Wu, G and Wan, D and Yang, Y and Li, Y and Niu, Z},
title = {Near telomere-to-telomere genome assembly of Lannea coromandelica provides insights into karyotype evolution in Anacardiaceae.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2026.02.010},
pmid = {41707861},
issn = {1673-8527},
}
RevDate: 2026-02-18
Telomere-to-telomere genome assembly and comprehensive mutation library facilitate bitter gourd breeding and functional genomics research.
Plant communications pii:S2590-3462(26)00087-8 [Epub ahead of print].
Bitter gourd (Momordica charantia L.), an economically vital vegetable crop with significant medicinal attributes, faces bottlenecks in genetic improvement due to scarce genomic resources and limited functional genomics tools. Here, we present a comprehensive genomic and functional resource platform to overcome these limitations. Utilizing PacBio HiFi and ONT ultra-long sequencing technologies combined with Hi-C, we achieved a telomere-to-telomere (T2T), gap-free genome assembly of the elite bitter gourd cultivar Y52, comprising 11 chromosomes with a final assembly size of 298.0 Mb. This high-quality assembly enabled accurate annotation of complex genomic regions, including centromeres characterized using chromatin immunoprecipitation (ChIP-seq). We constructed a large-scale EMS-induced mutant library consisting of 3,223 M1 plants and performed whole-genome resequencing on 320 mutants, identifying approximately 76,002 induced mutations affecting 13,984 genes. Leveraging this mutant population, we rapidly isolated the causal gene McEGY1 responsible for chlorotic leaf and fruit phenotypes using a MutMap-based method. Furthermore, we applied Bulked Segregant Analysis (BSA) and RNA-seq (BSR) to identify genomic regions and candidate genes underlying critical agronomic traits, including fruit length, fruit tubercle formation and powdery mildew resistance. Additionally, integrated transcriptomic and metabolomic analyses across multiple tissues and developmental stages generated comprehensive gene expression and metabolite accumulation profiles, elucidating tissue-specific regulatory networks. Finally, we integrated the genomic, mutant, transcriptomic, and metabolomic resources generated in this study to build Bittergourd DB (http://bittergourddb.omicsplant.cn/), a comprehensive platform to support bitter gourd functional genomics and molecular breeding. Collectively, our study provides an unprecedented genomic and functional resource, including a complete T2T reference genome, extensive EMS mutant library, trait-associated loci, and multi-omics maps, significantly accelerating bitter gourd functional genomics research and molecular breeding efforts.
Additional Links: PMID-41703933
Publisher:
PubMed:
Citation:
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@article {pmid41703933,
year = {2026},
author = {Zhang, Y and Wang, X and Wang, Y and Niu, Y and Han, X and Tan, J and Ma, X and Zhang, Q and Liu, J and Zhang, Z and Gao, W and Liang, W and Li, L and Liu, Z and Zhang, X and He, H and Yang, Y and Yu, R},
title = {Telomere-to-telomere genome assembly and comprehensive mutation library facilitate bitter gourd breeding and functional genomics research.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101779},
doi = {10.1016/j.xplc.2026.101779},
pmid = {41703933},
issn = {2590-3462},
abstract = {Bitter gourd (Momordica charantia L.), an economically vital vegetable crop with significant medicinal attributes, faces bottlenecks in genetic improvement due to scarce genomic resources and limited functional genomics tools. Here, we present a comprehensive genomic and functional resource platform to overcome these limitations. Utilizing PacBio HiFi and ONT ultra-long sequencing technologies combined with Hi-C, we achieved a telomere-to-telomere (T2T), gap-free genome assembly of the elite bitter gourd cultivar Y52, comprising 11 chromosomes with a final assembly size of 298.0 Mb. This high-quality assembly enabled accurate annotation of complex genomic regions, including centromeres characterized using chromatin immunoprecipitation (ChIP-seq). We constructed a large-scale EMS-induced mutant library consisting of 3,223 M1 plants and performed whole-genome resequencing on 320 mutants, identifying approximately 76,002 induced mutations affecting 13,984 genes. Leveraging this mutant population, we rapidly isolated the causal gene McEGY1 responsible for chlorotic leaf and fruit phenotypes using a MutMap-based method. Furthermore, we applied Bulked Segregant Analysis (BSA) and RNA-seq (BSR) to identify genomic regions and candidate genes underlying critical agronomic traits, including fruit length, fruit tubercle formation and powdery mildew resistance. Additionally, integrated transcriptomic and metabolomic analyses across multiple tissues and developmental stages generated comprehensive gene expression and metabolite accumulation profiles, elucidating tissue-specific regulatory networks. Finally, we integrated the genomic, mutant, transcriptomic, and metabolomic resources generated in this study to build Bittergourd DB (http://bittergourddb.omicsplant.cn/), a comprehensive platform to support bitter gourd functional genomics and molecular breeding. Collectively, our study provides an unprecedented genomic and functional resource, including a complete T2T reference genome, extensive EMS mutant library, trait-associated loci, and multi-omics maps, significantly accelerating bitter gourd functional genomics research and molecular breeding efforts.},
}
RevDate: 2026-02-17
Transient telomere uncapping triggers telomeric and subtelomeric rearrangements.
EMBO reports [Epub ahead of print].
Telomeres cap the extremities of linear chromosomes and prevent their detection as DNA damage. Telomere uncapping poses a profound threat to genome integrity, yet the immediate consequences of transient uncapping remain unclear. In Saccharomyces cerevisiae, the Cdc13-Stn1-Ten1 complex limits resection, preventing DNA damage checkpoint activation. Here, using the temperature-sensitive cdc13-1 allele, we demonstrate that transient telomere uncapping rapidly induces extensive genomic rearrangements despite a functional DNA damage checkpoint. Two distinct rearrangement signatures are observed in surviving cells: recombination of the subtelomeric region mostly involving the Y' elements, and massively elongated telomeres up to 10 kb, a ~ 30-fold increase. Long-read sequencing evidences Y' element losses/amplifications, terminal duplications, and telomeric-circle-driven amplifications of telomere repeats. Rearrangements unfold over multiple generations and require the homologous recombination factor Rad52, the Polδ subunit Pol32, and partially Rad51 and Rad59. Remarkably, survivors with elongated telomeres demonstrate a robust Rad52-dependent resistance to subsequent telomere uncapping. Our findings provide novel insights into the consequences of transient telomere uncapping for genome stability, a process that might contribute to subtelomere and telomere dynamics and evolution.
Additional Links: PMID-41703072
PubMed:
Citation:
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@article {pmid41703072,
year = {2026},
author = {Dudragne, L and Garrido, C and Ilioaia, O and Bernardes, JS and Xu, Z},
title = {Transient telomere uncapping triggers telomeric and subtelomeric rearrangements.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {41703072},
issn = {1469-3178},
support = {Programme Emergence(s)//Ville de Paris/ ; Emergence//Sorbonne Université (Sorbonne University)/ ; Subvention Recherche Scientifique 2022//Ligue Contre le Cancer (laliguecancer)/ ; ARCPJA202160003865//Fondation ARC pour la Recherche sur le Cancer (ARC)/ ; ARCPGA2023110007341_7967//Fondation ARC pour la Recherche sur le Cancer (ARC)/ ; ANR-24-CE12-7740-01//Agence Nationale de la Recherche (ANR)/ ; ANR-24-CE12-0083-03//Agence Nationale de la Recherche (ANR)/ ; },
abstract = {Telomeres cap the extremities of linear chromosomes and prevent their detection as DNA damage. Telomere uncapping poses a profound threat to genome integrity, yet the immediate consequences of transient uncapping remain unclear. In Saccharomyces cerevisiae, the Cdc13-Stn1-Ten1 complex limits resection, preventing DNA damage checkpoint activation. Here, using the temperature-sensitive cdc13-1 allele, we demonstrate that transient telomere uncapping rapidly induces extensive genomic rearrangements despite a functional DNA damage checkpoint. Two distinct rearrangement signatures are observed in surviving cells: recombination of the subtelomeric region mostly involving the Y' elements, and massively elongated telomeres up to 10 kb, a ~ 30-fold increase. Long-read sequencing evidences Y' element losses/amplifications, terminal duplications, and telomeric-circle-driven amplifications of telomere repeats. Rearrangements unfold over multiple generations and require the homologous recombination factor Rad52, the Polδ subunit Pol32, and partially Rad51 and Rad59. Remarkably, survivors with elongated telomeres demonstrate a robust Rad52-dependent resistance to subsequent telomere uncapping. Our findings provide novel insights into the consequences of transient telomere uncapping for genome stability, a process that might contribute to subtelomere and telomere dynamics and evolution.},
}
RevDate: 2026-02-17
A homozygote mutation in RPA2 associated with bone marrow failure, immunodeficiency, and telomere biology disorder.
European journal of human genetics : EJHG [Epub ahead of print].
Telomere biology disorders (TBDs) are characterized by bone marrow failure (BMF) and dysfunctional telomeres. So far, inherited mutations in 18 genes have been identified in TBDs. Here, we describe a child presenting with early BMF, immunodeficiency, and severely short and defective telomeres, carrying a homozygous splicing mutation (c.409-2 A > G; p.Q136_K138del) in RPA2 - a known replication factor and telomerase accessory factor. The Q136_K138del mutation is predicted to compromise the binding of RPA2 to the single-stranded telomeric DNA. Sequencing of single telomeres revealed that telomere variant repeats (TVRs), present also in healthy individuals, became more prominent in the short telomeres of the patient. Such TVRs may aggravate the telomere dysfunction due to lower affinity to the shelterin proteins. The severe telomere shortening and the activation of DNA damage response at telomeres indicate that this RPA2 mutation causes TBD in a similar manner to other known mutations and should be considered in patients displaying clinical TBD features.
Additional Links: PMID-41703052
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@article {pmid41703052,
year = {2026},
author = {Simon, AJ and Neustadter-Blackman, M and Lev, A and Nayshool, O and Kellerman, R and Glaser, F and Levy, S and Smoom, R and Barel, O and Mandola, A and Regev, M and Naor, S and Adam, E and Tzfati, Y and Somech, R},
title = {A homozygote mutation in RPA2 associated with bone marrow failure, immunodeficiency, and telomere biology disorder.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {41703052},
issn = {1476-5438},
support = {1342/23//Israel Science Foundation (ISF)/ ; 3115/19//Israel Science Foundation (ISF)/ ; },
abstract = {Telomere biology disorders (TBDs) are characterized by bone marrow failure (BMF) and dysfunctional telomeres. So far, inherited mutations in 18 genes have been identified in TBDs. Here, we describe a child presenting with early BMF, immunodeficiency, and severely short and defective telomeres, carrying a homozygous splicing mutation (c.409-2 A > G; p.Q136_K138del) in RPA2 - a known replication factor and telomerase accessory factor. The Q136_K138del mutation is predicted to compromise the binding of RPA2 to the single-stranded telomeric DNA. Sequencing of single telomeres revealed that telomere variant repeats (TVRs), present also in healthy individuals, became more prominent in the short telomeres of the patient. Such TVRs may aggravate the telomere dysfunction due to lower affinity to the shelterin proteins. The severe telomere shortening and the activation of DNA damage response at telomeres indicate that this RPA2 mutation causes TBD in a similar manner to other known mutations and should be considered in patients displaying clinical TBD features.},
}
RevDate: 2026-02-17
TRF2 Upregulates Protein Phosphatase 2A Subunit PPP2R2C to Attenuate DNA Damage Response at Telomeres and Pericentromeres Upon Replicative Stress.
Aging and disease pii:AD.2025.1249 [Epub ahead of print].
Telomeres and pericentromeres are regions of heterochromatin that are difficult to replicate. Telomeric binding factor 2 (TRF2) is a key telomere protective protein that acts against DNA damage at telomeres and allows the progression of replication forks through telomere chromatin, a region with heterochromatin features that is difficult to replicate. TRF2 is also required at pericentromeres for proper replication elongation. Here, we show that TRF2 positively regulates the activity of protein phosphatase 2A (PP2A) by activating the expression of PPP2R2C, a gene encoding an isoform of the regulatory subunit of PP2A with particularly elevated expression in neuronal tissues. Mechanistically, we provide evidence that TRF2 binds to an intronic interstitial telomeric sequence (ITS) of PPP2R2C with transactivation activity. Moreover, PPP2R2C is recruited to telomeres and pericentromeres during S phase and during replicative stress where it attenuates the DNA damage response. Finally, we show that the TRF2-dependent regulation of PPP2R2C expression plays an important role in maintaining neurodevelopment in zebrafish. These results reveal a mechanism required for normal neurodevelopment by which TRF2 attenuates DNA damage by upregulating PPP2R2C, thereby stimulating PP2A activity at two regions difficult to replicate: telomeres and pericentromeres.
Additional Links: PMID-41701876
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PubMed:
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@article {pmid41701876,
year = {2026},
author = {Zhai, X and Wang, C and Ying, Y and Leong, W and Chen, L and Wei, B and Cheng, X and Huang, S and Chen, Q and Lu, Y and Gilson, E and Ye, J},
title = {TRF2 Upregulates Protein Phosphatase 2A Subunit PPP2R2C to Attenuate DNA Damage Response at Telomeres and Pericentromeres Upon Replicative Stress.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1249},
pmid = {41701876},
issn = {2152-5250},
abstract = {Telomeres and pericentromeres are regions of heterochromatin that are difficult to replicate. Telomeric binding factor 2 (TRF2) is a key telomere protective protein that acts against DNA damage at telomeres and allows the progression of replication forks through telomere chromatin, a region with heterochromatin features that is difficult to replicate. TRF2 is also required at pericentromeres for proper replication elongation. Here, we show that TRF2 positively regulates the activity of protein phosphatase 2A (PP2A) by activating the expression of PPP2R2C, a gene encoding an isoform of the regulatory subunit of PP2A with particularly elevated expression in neuronal tissues. Mechanistically, we provide evidence that TRF2 binds to an intronic interstitial telomeric sequence (ITS) of PPP2R2C with transactivation activity. Moreover, PPP2R2C is recruited to telomeres and pericentromeres during S phase and during replicative stress where it attenuates the DNA damage response. Finally, we show that the TRF2-dependent regulation of PPP2R2C expression plays an important role in maintaining neurodevelopment in zebrafish. These results reveal a mechanism required for normal neurodevelopment by which TRF2 attenuates DNA damage by upregulating PPP2R2C, thereby stimulating PP2A activity at two regions difficult to replicate: telomeres and pericentromeres.},
}
RevDate: 2026-02-17
TRF-1 Mediates PRC2 Function at Ectopic Telomere Repeats in Neurospora crassa.
Molecular and cellular biology [Epub ahead of print].
Telomeres are crucial for maintaining chromosomal integrity and are characterized by repetitive DNA sequences, which may be stabilized by the shelterin protein complex or by formation of secondary structures, such as G-quadruplexes (G4 DNA). Frequently, subtelomeric regions are decorated with di- and tri-methylated lysine 27 on histone H3 (H3K27me), repressive marks catalyzed by Polycomb Repressive Complex 2 that are associated with facultative heterochromatin in many eukaryotes. Our previous work with the filamentous fungus Neurospora crassa demonstrated that native telomere repeats induce H3K27me at ectopic loci. Here we report investigations into the mechanism of this and demonstrate that some non-native telomere repeats can also induce H3K27me. Hi-C analyses demonstrated that ectopic telomeric repeats can interact with native telomeres. Chromatin immunoprecipitation (ChIP) experiments with an anti-G4-DNA antibody showed that establishment of H3K27me was not correlated with the presence of G4 DNA. Other ChIP experiments demonstrated that the telomere repeat-binding protein TRF-1, which has been demonstrated to be a member of the shelterin complex in other systems, binds to interstitial telomere repeats that induce H3K27me. Tethering experiments revealed that TRF-1 binding is sufficient to induce H3K27me. Together these results suggest that TRF-1 plays a crucial role in establishment of H3K27me, and thus repression, at telomere sequences.
Additional Links: PMID-41700018
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PubMed:
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@article {pmid41700018,
year = {2026},
author = {Mumford, CC and Painter, PD and McNaught, KJ and Tanizawa, H and Smith, NJ and Honda, S and Iwasaki, O and Tashiro, S and Noma, KI and Selker, EU},
title = {TRF-1 Mediates PRC2 Function at Ectopic Telomere Repeats in Neurospora crassa.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/10985549.2026.2627225},
pmid = {41700018},
issn = {1098-5549},
abstract = {Telomeres are crucial for maintaining chromosomal integrity and are characterized by repetitive DNA sequences, which may be stabilized by the shelterin protein complex or by formation of secondary structures, such as G-quadruplexes (G4 DNA). Frequently, subtelomeric regions are decorated with di- and tri-methylated lysine 27 on histone H3 (H3K27me), repressive marks catalyzed by Polycomb Repressive Complex 2 that are associated with facultative heterochromatin in many eukaryotes. Our previous work with the filamentous fungus Neurospora crassa demonstrated that native telomere repeats induce H3K27me at ectopic loci. Here we report investigations into the mechanism of this and demonstrate that some non-native telomere repeats can also induce H3K27me. Hi-C analyses demonstrated that ectopic telomeric repeats can interact with native telomeres. Chromatin immunoprecipitation (ChIP) experiments with an anti-G4-DNA antibody showed that establishment of H3K27me was not correlated with the presence of G4 DNA. Other ChIP experiments demonstrated that the telomere repeat-binding protein TRF-1, which has been demonstrated to be a member of the shelterin complex in other systems, binds to interstitial telomere repeats that induce H3K27me. Tethering experiments revealed that TRF-1 binding is sufficient to induce H3K27me. Together these results suggest that TRF-1 plays a crucial role in establishment of H3K27me, and thus repression, at telomere sequences.},
}
RevDate: 2026-02-16
Impact of telomere length alteration in chronic kidney disease patients of Pakistan: a case-control study and meta-analysis of 24,089 patients.
Acta clinica Belgica [Epub ahead of print].
BACKGROUND: Chronic kidney disease (CKD) is becoming a global health concern due to its rising prevalence owing to the complex interplay of environmental, genetic, and epigenetic factors. Leukocyte telomere length (LTL) is a potential indicator of biological age in age-related diseases. Our objective is to investigate the association between LTL and CKD in Pakistani population to systematically synthesize existing evidence by investigating previously reported studies.
MATERIAL AND METHODS: We conducted a case-control study (n = 166), aged 18-60 years. Relative LTL was measured using quantitative real-time PCR and expressed as telomere-to-single copy gene (T/S) ratios. Biochemical parameters and estimated glomerular filtration rate (eGFR) were assessed using standard methods. Multivariable linear regression adjusted for demographic and cardiometabolic factors was performed. A meta-analysis (11 studies, n = 24,089) were conducted.
RESULTS: Our results revealed significant LTL attrition in CKD patients compared to controls with a moderate effect size. Correlational analysis revealed that LTL positively correlated with eGFR (p-value = 0.038) and negatively correlated with urea and creatinine (p < 0.05). After adjustment for age, sex, body mass index, diabetes, smoking, hypertension, and LDL cholesterol, CKD status remained independently associated with shorter LTL. Meta-analysis demonstrated an overall trend toward shorter telomeres in CKD, although substantial heterogeneity and evidence of small study effects were observed. Subgroup analysis in Asian populations showed a consistent but less robust association.
CONCLUSION: LTL is associated with CKD, which may reflect systemic biological aging and disease burden rather than serving as a standalone clinical biomarker. Longitudinal studies are required to clarify causality and population-specific effects.
Additional Links: PMID-41697138
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@article {pmid41697138,
year = {2026},
author = {Tahir, M and Liaquat, A and Khalil, F and Tariq, Z and Javed, A and Irfan, A and Khan, MJ},
title = {Impact of telomere length alteration in chronic kidney disease patients of Pakistan: a case-control study and meta-analysis of 24,089 patients.},
journal = {Acta clinica Belgica},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/17843286.2026.2627250},
pmid = {41697138},
issn = {2295-3337},
abstract = {BACKGROUND: Chronic kidney disease (CKD) is becoming a global health concern due to its rising prevalence owing to the complex interplay of environmental, genetic, and epigenetic factors. Leukocyte telomere length (LTL) is a potential indicator of biological age in age-related diseases. Our objective is to investigate the association between LTL and CKD in Pakistani population to systematically synthesize existing evidence by investigating previously reported studies.
MATERIAL AND METHODS: We conducted a case-control study (n = 166), aged 18-60 years. Relative LTL was measured using quantitative real-time PCR and expressed as telomere-to-single copy gene (T/S) ratios. Biochemical parameters and estimated glomerular filtration rate (eGFR) were assessed using standard methods. Multivariable linear regression adjusted for demographic and cardiometabolic factors was performed. A meta-analysis (11 studies, n = 24,089) were conducted.
RESULTS: Our results revealed significant LTL attrition in CKD patients compared to controls with a moderate effect size. Correlational analysis revealed that LTL positively correlated with eGFR (p-value = 0.038) and negatively correlated with urea and creatinine (p < 0.05). After adjustment for age, sex, body mass index, diabetes, smoking, hypertension, and LDL cholesterol, CKD status remained independently associated with shorter LTL. Meta-analysis demonstrated an overall trend toward shorter telomeres in CKD, although substantial heterogeneity and evidence of small study effects were observed. Subgroup analysis in Asian populations showed a consistent but less robust association.
CONCLUSION: LTL is associated with CKD, which may reflect systemic biological aging and disease burden rather than serving as a standalone clinical biomarker. Longitudinal studies are required to clarify causality and population-specific effects.},
}
RevDate: 2026-02-16
CmpDate: 2026-02-16
NPM1 phosphorylation-mediated telomere maintenance via stabilization of POLD3 in ALT-positive osteosarcoma: unraveling mechanisms and therapeutic opportunities.
Theranostics, 16(8):4224-4244.
Maintaining telomere integrity is essential for cellular survival, and reactivation of telomerase or alternative lengthening of telomeres (ALT) represents a hallmark of cancer, ensuring replicative immortality. Osteosarcoma (OS), a malignancy in which many tumors rely on ALT for telomere maintenance, lacks effective therapeutic strategies targeting this pathway. This study aimed to identify and characterize novel molecular regulators of ALT activity and explore their potential as therapeutic targets in OS. Methods: Immunohistochemistry was performed to evaluate the expression of phosphorylated NPM1 (pT199-NPM1) in OS tissues. Functional experiments including NPM1 knockdown and rescue assays were conducted to assess the impact of NPM1 on break-induced telomere replication (BITR) and cell viability in ALT-positive cells. Mechanistic studies involving phosphorylation analysis, ubiquitination assays, and co-immunoprecipitation were used to determine how ATR-mediated phosphorylation of NPM1 regulates POLD3 stability and its interaction with the CST complex. Pharmacological screening was performed to identify compounds that inhibit ALT activity, followed by in vitro proliferation assays and in vivo mouse xenograft experiments to evaluate therapeutic efficacy and synergy with doxorubicin. Results: We identified pT199-NPM1 as a novel, highly expressed protein factor in ALT-positive OS tissues. NPM1 depletion impaired break-induced telomere replication and significantly reduced the viability of ALT-positive cells. ATR signaling phosphorylated NPM1 at Thr199, which stabilized POLD3 by preventing its ubiquitin-mediated degradation. Recruitment and function of pT199-NPM1 at telomeric damage sites required STN1, defining a CST/pT199-NPM1/POLD3 regulatory axis essential for ALT activity. Clinically, elevated Thr199 phosphorylation correlated with poor survival in OS patients, while expression of a phosphorylation-deficient T199A mutant failed to sustain ALT telomere maintenance. Pharmacological screening identified EPZ-6438, an EZH2 inhibitor, as a potent ALT suppressor that reduced NPM1 transcription, inhibited homologous recombination-mediated telomere synthesis, and suppressed OS cell proliferation. In mouse xenografts, EPZ-6438 enhanced OS cell sensitivity to doxorubicin, suggesting therapeutic synergy. Conclusions: This study uncovers a novel CST/pT199-NPM1/POLD3 regulatory module that is critical for ALT telomere maintenance in OS. Targeting NPM1 or its downstream effectors effectively suppresses ALT activity and enhances chemotherapy response. These findings provide new mechanistic insights into telomere regulation in ALT-positive tumors and highlight the therapeutic potential of NPM1-centered pathways in OS.
Additional Links: PMID-41695477
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Citation:
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@article {pmid41695477,
year = {2026},
author = {Zhao, R and Li, T and Yang, Q and Jiang, D and Xue, Y and Kou, H and Wang, Q and Wang, Y and Han, X and Ma, W and Wang, G and Feng, J and Han, X and Liu, Y and Jing, Y and Geng, X and Wang, F and Liu, Y and Zhang, Q and Wang, F},
title = {NPM1 phosphorylation-mediated telomere maintenance via stabilization of POLD3 in ALT-positive osteosarcoma: unraveling mechanisms and therapeutic opportunities.},
journal = {Theranostics},
volume = {16},
number = {8},
pages = {4224-4244},
pmid = {41695477},
issn = {1838-7640},
mesh = {*Osteosarcoma/metabolism/genetics/pathology/drug therapy ; Nucleophosmin/metabolism ; Humans ; Animals ; Phosphorylation ; Mice ; *Nuclear Proteins/metabolism/genetics ; Cell Line, Tumor ; *Telomere Homeostasis ; *Bone Neoplasms/metabolism/genetics/pathology/drug therapy ; *Telomere/metabolism ; Xenograft Model Antitumor Assays ; Female ; Cell Proliferation/drug effects ; Doxorubicin/pharmacology ; Male ; Mice, Nude ; },
abstract = {Maintaining telomere integrity is essential for cellular survival, and reactivation of telomerase or alternative lengthening of telomeres (ALT) represents a hallmark of cancer, ensuring replicative immortality. Osteosarcoma (OS), a malignancy in which many tumors rely on ALT for telomere maintenance, lacks effective therapeutic strategies targeting this pathway. This study aimed to identify and characterize novel molecular regulators of ALT activity and explore their potential as therapeutic targets in OS. Methods: Immunohistochemistry was performed to evaluate the expression of phosphorylated NPM1 (pT199-NPM1) in OS tissues. Functional experiments including NPM1 knockdown and rescue assays were conducted to assess the impact of NPM1 on break-induced telomere replication (BITR) and cell viability in ALT-positive cells. Mechanistic studies involving phosphorylation analysis, ubiquitination assays, and co-immunoprecipitation were used to determine how ATR-mediated phosphorylation of NPM1 regulates POLD3 stability and its interaction with the CST complex. Pharmacological screening was performed to identify compounds that inhibit ALT activity, followed by in vitro proliferation assays and in vivo mouse xenograft experiments to evaluate therapeutic efficacy and synergy with doxorubicin. Results: We identified pT199-NPM1 as a novel, highly expressed protein factor in ALT-positive OS tissues. NPM1 depletion impaired break-induced telomere replication and significantly reduced the viability of ALT-positive cells. ATR signaling phosphorylated NPM1 at Thr199, which stabilized POLD3 by preventing its ubiquitin-mediated degradation. Recruitment and function of pT199-NPM1 at telomeric damage sites required STN1, defining a CST/pT199-NPM1/POLD3 regulatory axis essential for ALT activity. Clinically, elevated Thr199 phosphorylation correlated with poor survival in OS patients, while expression of a phosphorylation-deficient T199A mutant failed to sustain ALT telomere maintenance. Pharmacological screening identified EPZ-6438, an EZH2 inhibitor, as a potent ALT suppressor that reduced NPM1 transcription, inhibited homologous recombination-mediated telomere synthesis, and suppressed OS cell proliferation. In mouse xenografts, EPZ-6438 enhanced OS cell sensitivity to doxorubicin, suggesting therapeutic synergy. Conclusions: This study uncovers a novel CST/pT199-NPM1/POLD3 regulatory module that is critical for ALT telomere maintenance in OS. Targeting NPM1 or its downstream effectors effectively suppresses ALT activity and enhances chemotherapy response. These findings provide new mechanistic insights into telomere regulation in ALT-positive tumors and highlight the therapeutic potential of NPM1-centered pathways in OS.},
}
MeSH Terms:
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*Osteosarcoma/metabolism/genetics/pathology/drug therapy
Nucleophosmin/metabolism
Humans
Animals
Phosphorylation
Mice
*Nuclear Proteins/metabolism/genetics
Cell Line, Tumor
*Telomere Homeostasis
*Bone Neoplasms/metabolism/genetics/pathology/drug therapy
*Telomere/metabolism
Xenograft Model Antitumor Assays
Female
Cell Proliferation/drug effects
Doxorubicin/pharmacology
Male
Mice, Nude
RevDate: 2026-02-16
CmpDate: 2026-02-16
Association between comprehensive exposure to multiple occupational hazardous factors and telomere length with hypertension in male steel workers: a case-control study.
Frontiers in public health, 14:1757027.
BACKGROUND: Steel workers are often exposed to various occupational hazards over the long term, which may be associated with hypertension. Previous studies mainly focused on the relationship between single occupational hazard and hypertension, but the comprehensive effects of multiple occupational hazards and the potential regulation of telomere length are still unclear. This study aims to investigate the relationship between combined exposure to multiple occupational hazards and hypertension in male steel workers, and to assess whether relative telomere length (RTL) plays a mediating role in this relationship.
METHODS: A 1:1 matched case-control study was conducted, with cases and controls matched on similar age (±2 years). The study included 350 hypertensive male steel workers and 350 normotensive controls. Occupational hazards [including heat, noise, dust, carbon monoxide (CO), shift work, and occupational stress] and relative telomere length (RTL) were assessed. An occupational hazardous factors score (OHFS) was constructed using the XGBoost model and SHapley Additive exPlanations (SHAP). Conditional logistic regression and quantile regression were used to analyze the associations. Mediation analysis was performed to evaluate the potential mediating effect of RTL in the relationship between OHFS and hypertension.
RESULTS: The risk of hypertension among male steel workers in the higher OHFS groups (24.74~, 38.98~, and ≥56.58) was 1.81, 2.17, and 3.46 times higher than that in the lower OHFS group (< 24.74), respectively (24.74~: OR = 1.81, 95% CI: 1.14-2.86; 38.98~: OR = 2.17, 95% CI: 1.39-3.39; ≥56.58: OR = 3.46, 95% CI: 2.18-5.49). The risk of hypertension among male steel workers in the shorter RTL group was 1.45 times higher than that in the longer RTL group (OR = 1.45, 95% CI: 1.04-2.03). A significant multiplicative interaction was observed between OHFS and RTL on hypertension (P < 0.001). Mediation analysis showed a partial mediating effect of RTL on the association between OHFS and hypertension (proportion mediated: 16.67%).
CONCLUSION: Among male steel workers, higher OHFS is associated with an increased risk of hypertension, and RTL plays a partial mediating role in the relationship between OHFS and hypertension.
Additional Links: PMID-41694504
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@article {pmid41694504,
year = {2026},
author = {Chen, X and Ma, X and Zhang, M and Liu, M and Xu, X and Luo, Z and Wang, N and Wu, J and Xue, L and Li, X},
title = {Association between comprehensive exposure to multiple occupational hazardous factors and telomere length with hypertension in male steel workers: a case-control study.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1757027},
pmid = {41694504},
issn = {2296-2565},
mesh = {Humans ; Male ; *Hypertension/epidemiology/etiology ; *Occupational Exposure/adverse effects/statistics & numerical data ; Case-Control Studies ; *Steel ; Adult ; Middle Aged ; Risk Factors ; *Telomere ; *Metal Workers ; *Occupational Diseases/epidemiology ; *Metallurgy ; },
abstract = {BACKGROUND: Steel workers are often exposed to various occupational hazards over the long term, which may be associated with hypertension. Previous studies mainly focused on the relationship between single occupational hazard and hypertension, but the comprehensive effects of multiple occupational hazards and the potential regulation of telomere length are still unclear. This study aims to investigate the relationship between combined exposure to multiple occupational hazards and hypertension in male steel workers, and to assess whether relative telomere length (RTL) plays a mediating role in this relationship.
METHODS: A 1:1 matched case-control study was conducted, with cases and controls matched on similar age (±2 years). The study included 350 hypertensive male steel workers and 350 normotensive controls. Occupational hazards [including heat, noise, dust, carbon monoxide (CO), shift work, and occupational stress] and relative telomere length (RTL) were assessed. An occupational hazardous factors score (OHFS) was constructed using the XGBoost model and SHapley Additive exPlanations (SHAP). Conditional logistic regression and quantile regression were used to analyze the associations. Mediation analysis was performed to evaluate the potential mediating effect of RTL in the relationship between OHFS and hypertension.
RESULTS: The risk of hypertension among male steel workers in the higher OHFS groups (24.74~, 38.98~, and ≥56.58) was 1.81, 2.17, and 3.46 times higher than that in the lower OHFS group (< 24.74), respectively (24.74~: OR = 1.81, 95% CI: 1.14-2.86; 38.98~: OR = 2.17, 95% CI: 1.39-3.39; ≥56.58: OR = 3.46, 95% CI: 2.18-5.49). The risk of hypertension among male steel workers in the shorter RTL group was 1.45 times higher than that in the longer RTL group (OR = 1.45, 95% CI: 1.04-2.03). A significant multiplicative interaction was observed between OHFS and RTL on hypertension (P < 0.001). Mediation analysis showed a partial mediating effect of RTL on the association between OHFS and hypertension (proportion mediated: 16.67%).
CONCLUSION: Among male steel workers, higher OHFS is associated with an increased risk of hypertension, and RTL plays a partial mediating role in the relationship between OHFS and hypertension.},
}
MeSH Terms:
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Humans
Male
*Hypertension/epidemiology/etiology
*Occupational Exposure/adverse effects/statistics & numerical data
Case-Control Studies
*Steel
Adult
Middle Aged
Risk Factors
*Telomere
*Metal Workers
*Occupational Diseases/epidemiology
*Metallurgy
RevDate: 2026-02-16
Oxidative Stress, Telomere Length, and Post-Intensive Care Syndrome in Mechanically Ventilated ICU Survivors.
Clinical nursing research [Epub ahead of print].
ICU survivors are at increased risk for persistent physical, cognitive, and psychological impairments, collectively known as Post-Intensive Care Syndrome (PICS). Critically ill patients, especially those on mechanical ventilation, experience increased oxidative stress burden, potentially contributing to telomere shortening. However, the relationship between oxidative stress, telomere attrition, and PICS-related outcomes remains unclear. Our objective was to examine associations among oxidative stress markers, telomere length, clinical characteristics, and PICS-related outcomes in mechanically ventilated ICU survivors. A cross-sectional study design was used. Blood samples were collected at two timepoints: study enrollment and within 48 hr of ICU discharge. PICS-related outcome measures were assessed within 48 hr of ICU discharge. Oxidative stress markers-including plasma protein carbonyls, vitamin C, reduced-to-oxidized glutathione ratio (GSH:GSSG), and total antioxidant capacity (TAC)-were quantified via ELISA. Three oxidative stress indices were calculated: vitamin C/GSH:GSSG, TAC/GSH:GSSG, and protein carbonyls/GSH:GSSG. Telomere length was determined using RT-qPCR. Clinical data included APACHE III and SOFA scores, ICU and hospital length of stay (LOS), and duration of mechanical ventilation. PICS-related outcomes included grip and foot strength, National Institutes of Health (NIH) Toolbox Cognition and Emotion assessments, and the Connor-Davidson Resilience Scale. Pearson's correlations were performed. Twenty-one participants were included in the final analysis. Plasma antioxidant status positively correlated with muscle strength and psychological resilience. Elevated plasma oxidant levels were associated with poorer cognitive outcomes. ICU LOS and duration of mechanical ventilation negatively correlated with muscle strength and cognitive performance. No significant correlations were observed between telomere length changes and PICS-related outcomes. Oxidative stress during acute critical illness may impede recovery and contribute to PICS. The lack of short-term associations with telomere length suggests that telomere-related effects on PICS may, possibly, become apparent over a longer post-ICU period.
Additional Links: PMID-41693051
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@article {pmid41693051,
year = {2026},
author = {Saugar, EE and Liang, Z and Alamian, A and Ferreira, T and Downs, CA},
title = {Oxidative Stress, Telomere Length, and Post-Intensive Care Syndrome in Mechanically Ventilated ICU Survivors.},
journal = {Clinical nursing research},
volume = {},
number = {},
pages = {10547738261417632},
doi = {10.1177/10547738261417632},
pmid = {41693051},
issn = {1552-3799},
abstract = {ICU survivors are at increased risk for persistent physical, cognitive, and psychological impairments, collectively known as Post-Intensive Care Syndrome (PICS). Critically ill patients, especially those on mechanical ventilation, experience increased oxidative stress burden, potentially contributing to telomere shortening. However, the relationship between oxidative stress, telomere attrition, and PICS-related outcomes remains unclear. Our objective was to examine associations among oxidative stress markers, telomere length, clinical characteristics, and PICS-related outcomes in mechanically ventilated ICU survivors. A cross-sectional study design was used. Blood samples were collected at two timepoints: study enrollment and within 48 hr of ICU discharge. PICS-related outcome measures were assessed within 48 hr of ICU discharge. Oxidative stress markers-including plasma protein carbonyls, vitamin C, reduced-to-oxidized glutathione ratio (GSH:GSSG), and total antioxidant capacity (TAC)-were quantified via ELISA. Three oxidative stress indices were calculated: vitamin C/GSH:GSSG, TAC/GSH:GSSG, and protein carbonyls/GSH:GSSG. Telomere length was determined using RT-qPCR. Clinical data included APACHE III and SOFA scores, ICU and hospital length of stay (LOS), and duration of mechanical ventilation. PICS-related outcomes included grip and foot strength, National Institutes of Health (NIH) Toolbox Cognition and Emotion assessments, and the Connor-Davidson Resilience Scale. Pearson's correlations were performed. Twenty-one participants were included in the final analysis. Plasma antioxidant status positively correlated with muscle strength and psychological resilience. Elevated plasma oxidant levels were associated with poorer cognitive outcomes. ICU LOS and duration of mechanical ventilation negatively correlated with muscle strength and cognitive performance. No significant correlations were observed between telomere length changes and PICS-related outcomes. Oxidative stress during acute critical illness may impede recovery and contribute to PICS. The lack of short-term associations with telomere length suggests that telomere-related effects on PICS may, possibly, become apparent over a longer post-ICU period.},
}
RevDate: 2026-02-14
Genetic insights into biological aging and myasthenia gravis: a Mendelian randomization study of telomere length, epigenetic clocks, and mitochondrial DNA copy number.
Clinical epigenetics pii:10.1186/s13148-026-02083-3 [Epub ahead of print].
BACKGROUND: Emerging epidemiological evidence shows myasthenia gravis (MG) is associated with age-related biological processes, but its mechanism of causality remains unexplained. This bidirectional Mendelian randomization (MR) study aimed to clarify the causal relationships between quantifiable biomarkers of aging and MG.
METHODS: We extracted genetic instrumental variables for three aging biomarkers: telomere length, epigenetic clocks, and mitochondrial DNA copy number (mtDNA-CN) and MG from the public GWAS databases. The main causal effect estimates were obtained by the inverse variance weighted method, and supplementary sensitivity analysis was used to evaluate potential heterogeneity and pleiotropy effects.
RESULTS: Overall, genetically predicted HannumAge and mtDNA-CN were associated with MG (OR = 0.909, 95% CI 0.834-0.991, P = 0.030; OR = 1.592, 95% CI 1.025-2.473, P = 0.039), though these associations did not survive false discovery rate (FDR) correction. Subgroup analyses showed a negative causal effect of HannumAge on early-onset MG (EOMG) (OR = 0.775, 95% CI 0.667-0.901, P = 0.001, PFDR =0.005), and a potential positive association of mtDNA-CN with late-onset MG (LOMG) (OR = 1.756, 95% CI 1.030-2.995, P = 0.039, PFDR =0.193). Reverse MR identified that EOMG causally increased epigenetic clocks (PhenoAge: OR = 1.056, 95% CI 1.004-1.111, P = 0.036; GrimAge: OR = 1.098, 95% CI 1.055-1.143, P < 0.001; HannumAge: OR = 1.100, 95% CI 1.058-1.144, P < 0.001), with the GrimAge and HannumAge association remaining significant after FDR correction. No evidence supported causal associations of MG/LOMG with aging biomarkers.
CONCLUSION: Our findings demonstrate a bidirectional causality between EOMG and epigenetic aging clocks, which indicates that there is a self-reinforcing pathophysiological cycle. The epigenetic age acceleration is both a driver and a result of the progression of EOMG. The correlation between mtDNA-CN and LOMG suggests that there may be a potential compensatory adaptation mechanism to combat chronic oxidative stress in age-related autoimmunity. These results highlight the complex and subtype-dependent contributions of biological aging to the autoimmune-mediated pathology of MG, and provide key mechanistic insights into the subtype-specific aging in MG.
Additional Links: PMID-41691323
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@article {pmid41691323,
year = {2026},
author = {Xiang, W and Luan, Y and Chen, K and He, T and Zhou, Q and Yang, H},
title = {Genetic insights into biological aging and myasthenia gravis: a Mendelian randomization study of telomere length, epigenetic clocks, and mitochondrial DNA copy number.},
journal = {Clinical epigenetics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13148-026-02083-3},
pmid = {41691323},
issn = {1868-7083},
support = {82171399//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Emerging epidemiological evidence shows myasthenia gravis (MG) is associated with age-related biological processes, but its mechanism of causality remains unexplained. This bidirectional Mendelian randomization (MR) study aimed to clarify the causal relationships between quantifiable biomarkers of aging and MG.
METHODS: We extracted genetic instrumental variables for three aging biomarkers: telomere length, epigenetic clocks, and mitochondrial DNA copy number (mtDNA-CN) and MG from the public GWAS databases. The main causal effect estimates were obtained by the inverse variance weighted method, and supplementary sensitivity analysis was used to evaluate potential heterogeneity and pleiotropy effects.
RESULTS: Overall, genetically predicted HannumAge and mtDNA-CN were associated with MG (OR = 0.909, 95% CI 0.834-0.991, P = 0.030; OR = 1.592, 95% CI 1.025-2.473, P = 0.039), though these associations did not survive false discovery rate (FDR) correction. Subgroup analyses showed a negative causal effect of HannumAge on early-onset MG (EOMG) (OR = 0.775, 95% CI 0.667-0.901, P = 0.001, PFDR =0.005), and a potential positive association of mtDNA-CN with late-onset MG (LOMG) (OR = 1.756, 95% CI 1.030-2.995, P = 0.039, PFDR =0.193). Reverse MR identified that EOMG causally increased epigenetic clocks (PhenoAge: OR = 1.056, 95% CI 1.004-1.111, P = 0.036; GrimAge: OR = 1.098, 95% CI 1.055-1.143, P < 0.001; HannumAge: OR = 1.100, 95% CI 1.058-1.144, P < 0.001), with the GrimAge and HannumAge association remaining significant after FDR correction. No evidence supported causal associations of MG/LOMG with aging biomarkers.
CONCLUSION: Our findings demonstrate a bidirectional causality between EOMG and epigenetic aging clocks, which indicates that there is a self-reinforcing pathophysiological cycle. The epigenetic age acceleration is both a driver and a result of the progression of EOMG. The correlation between mtDNA-CN and LOMG suggests that there may be a potential compensatory adaptation mechanism to combat chronic oxidative stress in age-related autoimmunity. These results highlight the complex and subtype-dependent contributions of biological aging to the autoimmune-mediated pathology of MG, and provide key mechanistic insights into the subtype-specific aging in MG.},
}
RevDate: 2026-02-14
A telomere-to-telomere genome assembly of Castanopsis orthacantha (Fagaceae).
Scientific data pii:10.1038/s41597-026-06787-2 [Epub ahead of print].
This study reported the first telomere-to-telomere (T2T) genome assembly of Castanopsis orthacantha, a keystone tree species with significant ecological and economic values endemic to the subtropical evergreen forests of southwestern China. Using multi-platform sequencing data and high-throughput chromosome conformation capture (Hi-C) scaffolding, we successfully generated a chromosome-scale assembly. The final assembly spanned 893.28 Mb, with a contig N50 of 76.19 Mb, indicating a high degree of continuity. Remarkably, 97.94% of the genome was successfully anchored to 12 chromosomes. Terminal telomeric repeat sequences were identified at both ends of all of the chromosomes, and the assembly contained only a single unresolved gap. A total of 35,978 protein-coding genes were detected in the assembly, with an average coding sequence (CDS) length of 1,116.3 bp. Genomic analysis further revealed that repetitive elements comprised 59.28% of the genome. The generation of this near-complete reference genome of C. orthacantha provides a critical genomic resource for advancing evolutionary study within the Fagaceae family and supports conservation genomics strategies aimed at the ecological restoration of this species.
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@article {pmid41690996,
year = {2026},
author = {Yin, S and Wang, H and Chu, H and Zhang, Y and Luo, C and Xu, Y and Gao, Y},
title = {A telomere-to-telomere genome assembly of Castanopsis orthacantha (Fagaceae).},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06787-2},
pmid = {41690996},
issn = {2052-4463},
support = {202401BA070001-126//Applied Basic Research Key Project of Yunnan (Applied Basic Research Key Project of Yunnan Province)/ ; 2024J0937//Yunnan Provincial Department of Education (Department of Education, Yunnan Province)/ ; },
abstract = {This study reported the first telomere-to-telomere (T2T) genome assembly of Castanopsis orthacantha, a keystone tree species with significant ecological and economic values endemic to the subtropical evergreen forests of southwestern China. Using multi-platform sequencing data and high-throughput chromosome conformation capture (Hi-C) scaffolding, we successfully generated a chromosome-scale assembly. The final assembly spanned 893.28 Mb, with a contig N50 of 76.19 Mb, indicating a high degree of continuity. Remarkably, 97.94% of the genome was successfully anchored to 12 chromosomes. Terminal telomeric repeat sequences were identified at both ends of all of the chromosomes, and the assembly contained only a single unresolved gap. A total of 35,978 protein-coding genes were detected in the assembly, with an average coding sequence (CDS) length of 1,116.3 bp. Genomic analysis further revealed that repetitive elements comprised 59.28% of the genome. The generation of this near-complete reference genome of C. orthacantha provides a critical genomic resource for advancing evolutionary study within the Fagaceae family and supports conservation genomics strategies aimed at the ecological restoration of this species.},
}
RevDate: 2026-02-14
Panax ginseng Meyer Supplementation and Potential Associations with Telomere Length and NAD+/NADH ratio in Middle-Aged Adults: An Exploratory Study.
Journal of ethnopharmacology pii:S0378-8741(26)00227-8 [Epub ahead of print].
In terms of anti-aging, ginseng has the effect of "lightening the body and prolonging the life" since ancient times. Although Panax ginseng Meyer (ginseng) has demonstrated anti-aging associations in experimental studies, clinical validation of its impact on telomere length and nicotinamide adenine dinucleotide (NAD+) / Nicotinamide adenine dinucleotide (NADH) ratio in healthy middle-aged individuals remains lacking.
AIM OF THE STUDY: Exploratory hypothesis-generating study on the association of ginseng on the telomere lengths and NAD+/NADH ratio of middle-aged adults.
METHODS: This study enrolled overweight middle-aged adults aged 45-50 years (Body mass index, BMI >24 kg/m[2]), involving two cohorts: high-dose short-term (6 g/day, 7 days; n=20) and low-dose long-term (3 g/day, 28 days; n=30), then they were followed up at 21 or 28 days after the completion of medication, respectively. Blood samples were collected before and after supplementation, and follow-up period. The primary outcomes: leukocyte telomere length and the NAD[+]/NADH ratio. The secondary outcomes: protection of telomeres 1 (POT1) expression, nicotinamide phosphoribosyltransferase (NAMPT) activities of peripheral blood mononuclear cells (PBMCs), reactive oxygen species (ROS), malondialdehyde (MDA), advanced glycation end-products (AGEs) and lactic acid (LA) levels. and scores on clinical scales [e.g., Pittsburgh sleep quality index (PSQI), Ascertain dementia 8 (AD8), Fatigue scale-14 (FS-14), International index of erectile function-5 (IIEF-5), and Kupperman index)].
RESULTS: The high-dose and low-dose groups showed a significant association with increased telomere length, POT1 expression, NAD+/NADH ratio, and NAMPT activity. The two cohorts also showed a significant association with reduced levels of ROS, MDA, AGEs, and LA, as well as improved scores on all clinical scales. Furthermore, the beneficial effects of the above indicators persisted during the follow-up period.
CONCLUSIONS: Ginseng supplementation is associated with telomere elongation and an increased NAD+/NADH ratio in middle-aged adults, and exerts beneficial effects on human overall health by improving potential biomarkers of aging.
Additional Links: PMID-41690428
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@article {pmid41690428,
year = {2026},
author = {Zhao, Y and Ni, W and Yao, S and Yu, S and Wang, C and Jin, C and Wang, X and Feng, J and Cui, Y and Yu, X and Wang, S and Zhao, D and Xiong, H and Ren, J and Liu, S and Liu, M},
title = {Panax ginseng Meyer Supplementation and Potential Associations with Telomere Length and NAD+/NADH ratio in Middle-Aged Adults: An Exploratory Study.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121376},
doi = {10.1016/j.jep.2026.121376},
pmid = {41690428},
issn = {1872-7573},
abstract = {In terms of anti-aging, ginseng has the effect of "lightening the body and prolonging the life" since ancient times. Although Panax ginseng Meyer (ginseng) has demonstrated anti-aging associations in experimental studies, clinical validation of its impact on telomere length and nicotinamide adenine dinucleotide (NAD+) / Nicotinamide adenine dinucleotide (NADH) ratio in healthy middle-aged individuals remains lacking.
AIM OF THE STUDY: Exploratory hypothesis-generating study on the association of ginseng on the telomere lengths and NAD+/NADH ratio of middle-aged adults.
METHODS: This study enrolled overweight middle-aged adults aged 45-50 years (Body mass index, BMI >24 kg/m[2]), involving two cohorts: high-dose short-term (6 g/day, 7 days; n=20) and low-dose long-term (3 g/day, 28 days; n=30), then they were followed up at 21 or 28 days after the completion of medication, respectively. Blood samples were collected before and after supplementation, and follow-up period. The primary outcomes: leukocyte telomere length and the NAD[+]/NADH ratio. The secondary outcomes: protection of telomeres 1 (POT1) expression, nicotinamide phosphoribosyltransferase (NAMPT) activities of peripheral blood mononuclear cells (PBMCs), reactive oxygen species (ROS), malondialdehyde (MDA), advanced glycation end-products (AGEs) and lactic acid (LA) levels. and scores on clinical scales [e.g., Pittsburgh sleep quality index (PSQI), Ascertain dementia 8 (AD8), Fatigue scale-14 (FS-14), International index of erectile function-5 (IIEF-5), and Kupperman index)].
RESULTS: The high-dose and low-dose groups showed a significant association with increased telomere length, POT1 expression, NAD+/NADH ratio, and NAMPT activity. The two cohorts also showed a significant association with reduced levels of ROS, MDA, AGEs, and LA, as well as improved scores on all clinical scales. Furthermore, the beneficial effects of the above indicators persisted during the follow-up period.
CONCLUSIONS: Ginseng supplementation is associated with telomere elongation and an increased NAD+/NADH ratio in middle-aged adults, and exerts beneficial effects on human overall health by improving potential biomarkers of aging.},
}
RevDate: 2026-02-14
Family member bereavement, salivary telomere length, and all-cause mortality in older adults: Findings from the Health and Retirement Study.
Psychoneuroendocrinology, 187:107792 pii:S0306-4530(26)00052-1 [Epub ahead of print].
The biological aging mechanisms by which loss exposure relates to mortality are not well-understood, particularly among communities of color. In this pre-registered, longitudinal study, we evaluated whether salivary telomeres mediate associations between loss burden-premature and cumulative exposure to family member deaths over the lifetime-and mortality. Leveraging a prospective sample of 4837 U.S. older adults from the Health and Retirement Study who recorded at least one kin death, we tested whether participants' loss burden related to their salivary telomeres 2 years later (linear regression models) and, in turn, predicted all-cause mortality 14 years later (Cox regression models). Models adjusted for covariates including family size, socioeconomic status, and baseline health including smoking. Telomeres did not mediate relationships between loss burden and mortality. Higher loss burden and shorter telomeres each predicted higher odds of mortality. Unexpectedly in race-stratified models, more childhood loss related to longer telomeres among Hispanic participants, and younger kin deaths related to longer telomeres among Black participants. Findings highlight the limitations of salivary telomeres in explaining racial health disparities and the need to identify biological aging mechanisms after loss among communities of color.
Additional Links: PMID-41690124
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PubMed:
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@article {pmid41690124,
year = {2026},
author = {Chang, M and Wilson, PA and Robles, TF},
title = {Family member bereavement, salivary telomere length, and all-cause mortality in older adults: Findings from the Health and Retirement Study.},
journal = {Psychoneuroendocrinology},
volume = {187},
number = {},
pages = {107792},
doi = {10.1016/j.psyneuen.2026.107792},
pmid = {41690124},
issn = {1873-3360},
abstract = {The biological aging mechanisms by which loss exposure relates to mortality are not well-understood, particularly among communities of color. In this pre-registered, longitudinal study, we evaluated whether salivary telomeres mediate associations between loss burden-premature and cumulative exposure to family member deaths over the lifetime-and mortality. Leveraging a prospective sample of 4837 U.S. older adults from the Health and Retirement Study who recorded at least one kin death, we tested whether participants' loss burden related to their salivary telomeres 2 years later (linear regression models) and, in turn, predicted all-cause mortality 14 years later (Cox regression models). Models adjusted for covariates including family size, socioeconomic status, and baseline health including smoking. Telomeres did not mediate relationships between loss burden and mortality. Higher loss burden and shorter telomeres each predicted higher odds of mortality. Unexpectedly in race-stratified models, more childhood loss related to longer telomeres among Hispanic participants, and younger kin deaths related to longer telomeres among Black participants. Findings highlight the limitations of salivary telomeres in explaining racial health disparities and the need to identify biological aging mechanisms after loss among communities of color.},
}
RevDate: 2026-02-13
Near telomere-to-telomere diploid genome assembly of Acrossocheilus wenchowensis.
Scientific data pii:10.1038/s41597-026-06752-z [Epub ahead of print].
Acrossocheilus wenchowensis is a lukewarm-water fish found in southern Chinese mountain streams, valued for both ornamental and edible purposes. We assembled a near telomere-to-telomere (T2T) genome using HiFi, ONT, Hi-C and Illumina data. The assembly is approximately 870.69 Mb with a contig N50 of about 21.28 Mb. Among these, 14 chromosomes in Hap1 and 15 chromosomes in Hap2 have reached T2T levels. A total of 24,909 protein-coding genes were predicted in Hap1 and 24,496 in Hap2, with BUSCO scores of 97.4% and 97.6%, respectively. A conserved centromeric satellite sequence (262 bp) derived from an LTR transposon was identified. Comparative genomics showed that Acrossocheilus and Onychostoma diverged approximately 13.7 million years ago (Mya), while A. wenchowensis diverged from A. fasciatus about 5.25 Mya. Resequencing of four geographic populations of A. wenchowensis revealed distinct genetic structure in the LY group compared to the other populations based on SNP and InDel analysis. This genome provides a framework for diploid T2T studies in fish and supports further functional genomics research.
Additional Links: PMID-41688479
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@article {pmid41688479,
year = {2026},
author = {Xue, L and Luo, M and Wang, H and Zhu, W and Chen, D and Zeng, G and Liao, M and Zhao, J and Wu, B and Xu, L and Dong, Z},
title = {Near telomere-to-telomere diploid genome assembly of Acrossocheilus wenchowensis.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06752-z},
pmid = {41688479},
issn = {2052-4463},
abstract = {Acrossocheilus wenchowensis is a lukewarm-water fish found in southern Chinese mountain streams, valued for both ornamental and edible purposes. We assembled a near telomere-to-telomere (T2T) genome using HiFi, ONT, Hi-C and Illumina data. The assembly is approximately 870.69 Mb with a contig N50 of about 21.28 Mb. Among these, 14 chromosomes in Hap1 and 15 chromosomes in Hap2 have reached T2T levels. A total of 24,909 protein-coding genes were predicted in Hap1 and 24,496 in Hap2, with BUSCO scores of 97.4% and 97.6%, respectively. A conserved centromeric satellite sequence (262 bp) derived from an LTR transposon was identified. Comparative genomics showed that Acrossocheilus and Onychostoma diverged approximately 13.7 million years ago (Mya), while A. wenchowensis diverged from A. fasciatus about 5.25 Mya. Resequencing of four geographic populations of A. wenchowensis revealed distinct genetic structure in the LY group compared to the other populations based on SNP and InDel analysis. This genome provides a framework for diploid T2T studies in fish and supports further functional genomics research.},
}
RevDate: 2026-02-13
CmpDate: 2026-02-13
Telomere Shortening Drives Atrial Fibrillation Through VCAM-1 Mediated Atrial Electrical and Structural Remodeling.
Aging cell, 25(2):e70417.
Telomere shortening is a hallmark of aging and has been implicated in cardiovascular disease, but its mechanistic link to atrial fibrillation (AF) remains elusive. Using a high-throughput, single-gene-calibrated dot blot assay, we developed to quantify leukocyte telomere length (LTL). In age-stratified analyses, shorter LTL was associated with AF predominantly in individuals younger than 70 years. In telomerase-deficient (TERT[-/-]) mice with telomere dysfunction, higher AF inducibility, atrial electrical conduction slowing, and atrial fibrosis were observed. Transcriptomic profiling revealed significant alterations in extracellular matrix and cell adhesion pathways in response to telomere dysfunction. Subsequent validation identified vascular cell adhesion molecule-1 (VCAM-1) as a potential mediator linking telomere shortening to AF-related atrial remodeling. Functional inhibition of VCAM-1 reversed electrophysiological abnormalities, attenuated atrial fibrosis, normalized ECM gene expression-including Col1α1, α-SMA, and CD168-and reduced AF susceptibility by 30%. These findings establish a telomere-VCAM-1 axis that drives atrial remodeling and arrhythmogenesis in aging, and position VCAM-1 as a candidate therapeutic target for age-related AF.
Additional Links: PMID-41685883
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@article {pmid41685883,
year = {2026},
author = {Wang, Z and Zhao, R and Wang, Y and Zhang, N and Yang, Q and Zhou, Z and Jiang, D and Zhang, X and Yuan, J and Zheng, Y and Song, W and Liu, D and Liu, X and Yuan, K and Tse, G and Lip, GYH and Liu, T and Wang, F},
title = {Telomere Shortening Drives Atrial Fibrillation Through VCAM-1 Mediated Atrial Electrical and Structural Remodeling.},
journal = {Aging cell},
volume = {25},
number = {2},
pages = {e70417},
doi = {10.1111/acel.70417},
pmid = {41685883},
issn = {1474-9726},
support = {32170762//National Natural Science Foundation of China/ ; 82170327//National Natural Science Foundation of China/ ; 82370332//National Natural Science Foundation of China/ ; 31771520//National Natural Science Foundation of China/ ; 92149302//National Natural Science Foundation of China/ ; 82072331//National Natural Science Foundation of China/ ; 82271265//National Natural Science Foundation of China/ ; 19YFZCSY00600//Scientific Research Program of Tianjin Municipal Education Commission 2020KJ200 and the Tianjin Health Research Project/ ; 19JCJQJC63500//Natural Science Foundation of Tianjin city/ ; 23JCZDJC00270//Natural Science Foundation of Tianjin city/ ; 24JCQNJC00820//Natural Science Foundation of Tianjin city/ ; 25JCZDJC00510//Natural Science Foundation of Tianjin city/ ; 2025-JKCS-23//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; 2021-I2M-1-042//CAMS innovation Fund for Medical Sciences/ ; 2022-I2M-2-003//CAMS innovation Fund for Medical Sciences/ ; 2022-I2M-2-008//CAMS innovation Fund for Medical Sciences/ ; 2023KJ038//Scientific Research Program of Tianjin Municipal Education Commission/ ; },
mesh = {*Atrial Fibrillation/genetics/physiopathology/metabolism/pathology ; *Vascular Cell Adhesion Molecule-1/metabolism/genetics ; Animals ; Mice ; Humans ; *Atrial Remodeling/genetics ; *Telomere Shortening/genetics ; Male ; *Heart Atria/physiopathology/pathology/metabolism ; Aged ; Female ; Telomerase/deficiency/metabolism/genetics ; Middle Aged ; },
abstract = {Telomere shortening is a hallmark of aging and has been implicated in cardiovascular disease, but its mechanistic link to atrial fibrillation (AF) remains elusive. Using a high-throughput, single-gene-calibrated dot blot assay, we developed to quantify leukocyte telomere length (LTL). In age-stratified analyses, shorter LTL was associated with AF predominantly in individuals younger than 70 years. In telomerase-deficient (TERT[-/-]) mice with telomere dysfunction, higher AF inducibility, atrial electrical conduction slowing, and atrial fibrosis were observed. Transcriptomic profiling revealed significant alterations in extracellular matrix and cell adhesion pathways in response to telomere dysfunction. Subsequent validation identified vascular cell adhesion molecule-1 (VCAM-1) as a potential mediator linking telomere shortening to AF-related atrial remodeling. Functional inhibition of VCAM-1 reversed electrophysiological abnormalities, attenuated atrial fibrosis, normalized ECM gene expression-including Col1α1, α-SMA, and CD168-and reduced AF susceptibility by 30%. These findings establish a telomere-VCAM-1 axis that drives atrial remodeling and arrhythmogenesis in aging, and position VCAM-1 as a candidate therapeutic target for age-related AF.},
}
MeSH Terms:
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*Atrial Fibrillation/genetics/physiopathology/metabolism/pathology
*Vascular Cell Adhesion Molecule-1/metabolism/genetics
Animals
Mice
Humans
*Atrial Remodeling/genetics
*Telomere Shortening/genetics
Male
*Heart Atria/physiopathology/pathology/metabolism
Aged
Female
Telomerase/deficiency/metabolism/genetics
Middle Aged
RevDate: 2026-02-13
An Orally Available Telomeric G-Quadruplex Ligand Induces Telomere Crisis and Dual DNA/RNA-Sensing Innate Immunity for Cancer Therapy.
Journal of medicinal chemistry [Epub ahead of print].
Telomere crisis is a potent intrinsic barrier against unlimited cancer cell proliferation, offering a promising anticancer strategy. While recent work has implicated both the cGAS-STING DNA-sensing and the TERRA-ZBP1 RNA-sensing pathways, revealing new therapeutic opportunities. Here, we report CA11, an orally bioavailable quinazoline derivative, discovered via a G-quadruplex (G4)-focused screening platform. We demonstrate that pharmacological stabilization of telomeric G4s by CA11 provokes a telomere crisis-like phenotype. Mechanistically, these events are associated with the coordinated activation of dual DNA/RNA-sensing innate immune pathways. This dual activation is linked to a potent innate immune response and autophagy, culminating in broad antiproliferative effects across diverse cancer cell lines. In vivo, oral administration of CA11 suppresses tumor growth by enhancing innate immunity, and is well tolerated systemically. Our findings establish CA11 as the first-in-class and orally activated telomeric G4 ligand that pharmacologically induces telomere crisis for cancer therapy.
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@article {pmid41685785,
year = {2026},
author = {Cai, JH and Shi, YH and Yang, DY and Huang, WY and Liu, Y and Zhong, LT and Zhang, JJ and Gong, Z and Lu, YY and Lin, JH and Li, ML and Li, Z and Chai, GH and Ou, TM and Tan, JH and Huang, ZS and Chen, SB},
title = {An Orally Available Telomeric G-Quadruplex Ligand Induces Telomere Crisis and Dual DNA/RNA-Sensing Innate Immunity for Cancer Therapy.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c03148},
pmid = {41685785},
issn = {1520-4804},
abstract = {Telomere crisis is a potent intrinsic barrier against unlimited cancer cell proliferation, offering a promising anticancer strategy. While recent work has implicated both the cGAS-STING DNA-sensing and the TERRA-ZBP1 RNA-sensing pathways, revealing new therapeutic opportunities. Here, we report CA11, an orally bioavailable quinazoline derivative, discovered via a G-quadruplex (G4)-focused screening platform. We demonstrate that pharmacological stabilization of telomeric G4s by CA11 provokes a telomere crisis-like phenotype. Mechanistically, these events are associated with the coordinated activation of dual DNA/RNA-sensing innate immune pathways. This dual activation is linked to a potent innate immune response and autophagy, culminating in broad antiproliferative effects across diverse cancer cell lines. In vivo, oral administration of CA11 suppresses tumor growth by enhancing innate immunity, and is well tolerated systemically. Our findings establish CA11 as the first-in-class and orally activated telomeric G4 ligand that pharmacologically induces telomere crisis for cancer therapy.},
}
RevDate: 2026-02-13
Changes in telomere length and mitochondrial DNA copy number in the colorectal adenoma-carcinoma sequence.
Mutagenesis pii:8482673 [Epub ahead of print].
Colorectal adenomas are anomalous growths of the intestinal epithelium and are considered precursors to colorectal cancer (CRC). Identifying early-stage CRC biomarkers is essential for reducing its high mortality rate. This study hypothesizes that the association of telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) could serve as a biomarker for the adenoma or CRC formation. TL, mtDNA-CN, TERT and TFAM expressions were studied in 132 adenoma and 95 early-stage CRC patients. TL and mtDNA-CN were measured by multiplex quantitative polymerase chain reaction (qPCR). Expression of TERT and TFAM was measured by reverse transcription (RT)-qPCR. Significant TL shortening was observed in adenomas (p=8.96e-14), TNM I (p=3.49e-05), and TNM II (p=2.29e-04) stages compared to the adjacent mucosa. This tendency was also contingent on TERT expression. Differential TFAM expression was observed in all groups, but an elevated relative mtDNA-CN was, compared to the adjacent mucosa, detected only in adenomas (p=1.50e-08), where it correlated with TL (p=4.10e-03). Notably, mtDNA-CN levels were significantly higher in adenomas than in early-stage tumors (TNM I, p=2.00e-02; TNM II, p=2.40e-02), suggesting a progressive decline during tumorigenesis. We have provided fresh insights into the crosstalk between telomere and mitochondrial biology in CRC precursors. These findings hold promise in understanding adenoma formation and CRC progression, as mtDNA-CN elevation and its association with TL were specific to precancerous lesions and were lost with progression to tumor.
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@article {pmid41685770,
year = {2026},
author = {Valickova, A and Tomasova, K and Balounova, K and Horak, J and Kroupa, M and Hanak, P and Danesova, N and Jungwirth, J and Kral, J and Hucl, T and Kohout, P and Summerova, S and Schneiderova, M and Vodickova, L and Vodicka, P and Vymetalkova, V and Vodenkova, S},
title = {Changes in telomere length and mitochondrial DNA copy number in the colorectal adenoma-carcinoma sequence.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/geag009},
pmid = {41685770},
issn = {1464-3804},
abstract = {Colorectal adenomas are anomalous growths of the intestinal epithelium and are considered precursors to colorectal cancer (CRC). Identifying early-stage CRC biomarkers is essential for reducing its high mortality rate. This study hypothesizes that the association of telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) could serve as a biomarker for the adenoma or CRC formation. TL, mtDNA-CN, TERT and TFAM expressions were studied in 132 adenoma and 95 early-stage CRC patients. TL and mtDNA-CN were measured by multiplex quantitative polymerase chain reaction (qPCR). Expression of TERT and TFAM was measured by reverse transcription (RT)-qPCR. Significant TL shortening was observed in adenomas (p=8.96e-14), TNM I (p=3.49e-05), and TNM II (p=2.29e-04) stages compared to the adjacent mucosa. This tendency was also contingent on TERT expression. Differential TFAM expression was observed in all groups, but an elevated relative mtDNA-CN was, compared to the adjacent mucosa, detected only in adenomas (p=1.50e-08), where it correlated with TL (p=4.10e-03). Notably, mtDNA-CN levels were significantly higher in adenomas than in early-stage tumors (TNM I, p=2.00e-02; TNM II, p=2.40e-02), suggesting a progressive decline during tumorigenesis. We have provided fresh insights into the crosstalk between telomere and mitochondrial biology in CRC precursors. These findings hold promise in understanding adenoma formation and CRC progression, as mtDNA-CN elevation and its association with TL were specific to precancerous lesions and were lost with progression to tumor.},
}
RevDate: 2026-02-13
CmpDate: 2026-02-13
Molecular Mechanisms of Accelerated Ageing in Geriatric Depression: Interplay of Telomere Attrition, Mitochondrial Dysfunction and Cellular Senescence.
International journal of molecular sciences, 27(3): pii:ijms27031613.
Late-life depression is a prevalent and debilitating disorder. It differs significantly from depression in younger adults and often co-occurs with cognitive decline and increased physical frailty. This narrative review explores the role of accelerated biological ageing in late-life depression. We examine evidence linking three interconnected processes, namely telomere attrition, mitochondrial dysfunction and cellular senescence, to the pathophysiology of late-life depression. Excessive attrition of telomeres may serve as a biomarker of accumulated stress and cellular ageing. Mitochondrial dysfunction not only reduces energy production but also promotes oxidative stress and inflammation that increase neuroinflammatory pathways and synaptic loss. Increased cellular senescence further induces senescence-associated secretory phenotype factors that drive chronic inflammation and neuronal loss. Together, these processes create a cycle of cellular stress, persistent inflammation and damage to brain circuits involved in late-life depression. We additionally highlight potential limitations in current findings and propose a roadmap for future research to better elucidate the mechanistic dysfunction of late-life depression. These include the need for evaluation in long-term prospective cohort studies, improved tools to better correlate blood-based markers with changes in disease-relevant brain tissues and regions, and trials that test treatment and lifestyle modifications that are targeted at ageing biomarkers.
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@article {pmid41684031,
year = {2026},
author = {Revi Shanker, P and Dorajoo, R},
title = {Molecular Mechanisms of Accelerated Ageing in Geriatric Depression: Interplay of Telomere Attrition, Mitochondrial Dysfunction and Cellular Senescence.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
doi = {10.3390/ijms27031613},
pmid = {41684031},
issn = {1422-0067},
mesh = {Humans ; *Cellular Senescence ; *Mitochondria/metabolism/pathology/genetics ; *Aging/genetics/metabolism/pathology ; *Telomere/metabolism/genetics ; *Depression/metabolism/genetics/pathology ; Oxidative Stress ; Aged ; Animals ; *Telomere Shortening ; Biomarkers ; },
abstract = {Late-life depression is a prevalent and debilitating disorder. It differs significantly from depression in younger adults and often co-occurs with cognitive decline and increased physical frailty. This narrative review explores the role of accelerated biological ageing in late-life depression. We examine evidence linking three interconnected processes, namely telomere attrition, mitochondrial dysfunction and cellular senescence, to the pathophysiology of late-life depression. Excessive attrition of telomeres may serve as a biomarker of accumulated stress and cellular ageing. Mitochondrial dysfunction not only reduces energy production but also promotes oxidative stress and inflammation that increase neuroinflammatory pathways and synaptic loss. Increased cellular senescence further induces senescence-associated secretory phenotype factors that drive chronic inflammation and neuronal loss. Together, these processes create a cycle of cellular stress, persistent inflammation and damage to brain circuits involved in late-life depression. We additionally highlight potential limitations in current findings and propose a roadmap for future research to better elucidate the mechanistic dysfunction of late-life depression. These include the need for evaluation in long-term prospective cohort studies, improved tools to better correlate blood-based markers with changes in disease-relevant brain tissues and regions, and trials that test treatment and lifestyle modifications that are targeted at ageing biomarkers.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Cellular Senescence
*Mitochondria/metabolism/pathology/genetics
*Aging/genetics/metabolism/pathology
*Telomere/metabolism/genetics
*Depression/metabolism/genetics/pathology
Oxidative Stress
Aged
Animals
*Telomere Shortening
Biomarkers
RevDate: 2026-02-13
CmpDate: 2026-02-13
ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels.
Cancers, 18(3): pii:cancers18030499.
BACKGROUND/OBJECTIVES: Approximately 10-15% of cancers rely on Alternate Lengthening of Telomeres (ALT), which is a telomerase-independent, BIR (Break-Induced Replication)-based pathway for maintaining long-term replicative potential.
METHODS: As ALT is over-represented in mesenchymal-type tumors, we investigated, via RNA-seq, the extent to which the EMT-promoting factor ZEB1 regulates this pathway.
RESULTS: The ALT-associated genes targeted by ZEB1, including PML, RMI2, POLD4, RPA3 (induced), SLX4, and WRN (repressed), in the aggregate, suggest that it regulates ALT at multiple steps in that pathway. ZEB1-deficient cells showed a significant reduction in telomere length as well as in two hallmarks of ALT, C-circle levels and the size and number of ALT-associated PML Bodies (APBs), which are the telomere-aggregating compartments in which BIR occurs. As one of the most highly regulated genetic targets of ZEB1 was the pro-epithelial alternative splicing factor ESRP1, we investigated whether the repression of this factor was required to generate the PML splice variant isoform IV, which is the major structural component of APBs. We found an inverse relationship between the expression of this protein and levels of PML isoform IV mRNA.
CONCLUSIONS: These findings suggest a novel role for ZEB1 in promoting ALT both transcriptionally and post-transcriptionally at multiple levels.
Additional Links: PMID-41681971
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@article {pmid41681971,
year = {2026},
author = {Genetta, TL and Perez-Medero, JD and Jang, H and Zhang, T and Hussain, BA and Larner, JM},
title = {ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels.},
journal = {Cancers},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/cancers18030499},
pmid = {41681971},
issn = {2072-6694},
support = {1R01CA259054-01A1//NIH USA/ ; },
abstract = {BACKGROUND/OBJECTIVES: Approximately 10-15% of cancers rely on Alternate Lengthening of Telomeres (ALT), which is a telomerase-independent, BIR (Break-Induced Replication)-based pathway for maintaining long-term replicative potential.
METHODS: As ALT is over-represented in mesenchymal-type tumors, we investigated, via RNA-seq, the extent to which the EMT-promoting factor ZEB1 regulates this pathway.
RESULTS: The ALT-associated genes targeted by ZEB1, including PML, RMI2, POLD4, RPA3 (induced), SLX4, and WRN (repressed), in the aggregate, suggest that it regulates ALT at multiple steps in that pathway. ZEB1-deficient cells showed a significant reduction in telomere length as well as in two hallmarks of ALT, C-circle levels and the size and number of ALT-associated PML Bodies (APBs), which are the telomere-aggregating compartments in which BIR occurs. As one of the most highly regulated genetic targets of ZEB1 was the pro-epithelial alternative splicing factor ESRP1, we investigated whether the repression of this factor was required to generate the PML splice variant isoform IV, which is the major structural component of APBs. We found an inverse relationship between the expression of this protein and levels of PML isoform IV mRNA.
CONCLUSIONS: These findings suggest a novel role for ZEB1 in promoting ALT both transcriptionally and post-transcriptionally at multiple levels.},
}
RevDate: 2026-02-13
CmpDate: 2026-02-13
Leukocyte Telomere Length Variants Are Independently Associated with Survival of Patients with Colorectal Cancer.
Cancers, 18(3): pii:cancers18030490.
Background and aims: Aberrations in telomere length can have important implications in cancer. Using a cohort of 1007 patients, we investigated whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival. We also investigated whether some telomere maintenance genes are associated with survival in these patients. Methods: The Biobank for Gastrointestinal Health Research (BGHR), an ongoing project involving collection of biospecimens at the Mayo Clinic, was utilized to obtain data from patients diagnosed with stage II or III CRC. Blood samples were collected prior to chemotherapy/radiation and DNA was extracted for measuring median LTL. The main outcome measures were overall survival (OS) and disease-free survival (DFS) by disease stage. Results: A significant inverse relationship was observed with patient age and LTL (spearman correlation coefficient (r) = -0.48, 95%; p = 1.13 × 10[-58]). Females had significantly longer LTL than males (p = 3.97 × 10[-5]). The rs1317082 SNP in the TERC gene was significantly associated with both OS and DFS in combined stage II and stage III patients (p = 0.017 and p = 0.023, respectively). A statistically significant association of the OBFC1 SNP (rs9419958) was observed for OS for the combined stage II and stage III patients (p = 0.016). Importantly, LTL was significantly associated with both OS and DFS (p = 0.008 and 0.044 respectively) in combined stage II and stage III patients. Conclusions: Our results show that LTL is predictive of OS and DFS for stage II and III CRC patients, particularly over a longer follow-up, extending beyond five years after a diagnosis of CRC, and certain SNPs in genes involved in telomere maintenance are significantly associated with patient outcomes, independent of telomere length.
Additional Links: PMID-41681962
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@article {pmid41681962,
year = {2026},
author = {Sarkar, G and Chen, J and Sood, S and Fischer, K and Kossick, K and Schupack, D and Graham, R and Druliner, B and Heydari, Z and Helgeson, L and Cruz Garcia, E and Cawthon, R and Boardman, L},
title = {Leukocyte Telomere Length Variants Are Independently Associated with Survival of Patients with Colorectal Cancer.},
journal = {Cancers},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/cancers18030490},
pmid = {41681962},
issn = {2072-6694},
support = {Individualizing colorectal cancer patient care//Individualizing colorectal cancer patient care/ ; P30DK084567//Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology/ ; },
abstract = {Background and aims: Aberrations in telomere length can have important implications in cancer. Using a cohort of 1007 patients, we investigated whether leukocyte telomere length (LTL) in patients with colorectal cancer (CRC) is associated with survival. We also investigated whether some telomere maintenance genes are associated with survival in these patients. Methods: The Biobank for Gastrointestinal Health Research (BGHR), an ongoing project involving collection of biospecimens at the Mayo Clinic, was utilized to obtain data from patients diagnosed with stage II or III CRC. Blood samples were collected prior to chemotherapy/radiation and DNA was extracted for measuring median LTL. The main outcome measures were overall survival (OS) and disease-free survival (DFS) by disease stage. Results: A significant inverse relationship was observed with patient age and LTL (spearman correlation coefficient (r) = -0.48, 95%; p = 1.13 × 10[-58]). Females had significantly longer LTL than males (p = 3.97 × 10[-5]). The rs1317082 SNP in the TERC gene was significantly associated with both OS and DFS in combined stage II and stage III patients (p = 0.017 and p = 0.023, respectively). A statistically significant association of the OBFC1 SNP (rs9419958) was observed for OS for the combined stage II and stage III patients (p = 0.016). Importantly, LTL was significantly associated with both OS and DFS (p = 0.008 and 0.044 respectively) in combined stage II and stage III patients. Conclusions: Our results show that LTL is predictive of OS and DFS for stage II and III CRC patients, particularly over a longer follow-up, extending beyond five years after a diagnosis of CRC, and certain SNPs in genes involved in telomere maintenance are significantly associated with patient outcomes, independent of telomere length.},
}
RevDate: 2026-02-13
Telomere Length, Cortisol, Body Composition, Hemodynamics and Dance: An Exploratory Analysis In 18-to-83-Year-Olds - Corrigendum.
Medicine and science in sports and exercise, 58(3):634.
Additional Links: PMID-41681008
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@article {pmid41681008,
year = {2026},
author = {},
title = {Telomere Length, Cortisol, Body Composition, Hemodynamics and Dance: An Exploratory Analysis In 18-to-83-Year-Olds - Corrigendum.},
journal = {Medicine and science in sports and exercise},
volume = {58},
number = {3},
pages = {634},
doi = {10.1249/MSS.0000000000003933},
pmid = {41681008},
issn = {1530-0315},
}
RevDate: 2026-02-12
Telomere to telomere level genome assembly of the Yarkand hare (Lepus yarkandensis).
Scientific data pii:10.1038/s41597-026-06815-1 [Epub ahead of print].
The Yarkand hare (Lepus yarkandensis) is endemic to the Tarim Basin in Xinjiang, China. It is a key species and a critical component of the Tarim Basin ecosystems. However, the lack of a reference genome has hindered evolutionary and genetic studies of this species. Here, we assembled a telomere-to-telomere (T2T) genome of the Yarkand hare (LepYark_1.0) using PacBio HiFi, Nanopore, and Hi-C sequencing. The assembled genome size is approximately 2.70 Gb, with a scaffold N50 of 126.86 Mb. About 94.88% of the assembled sequences could be anchored to 24 pseudo-chromosomes, with a BUSCO assessment indicating a completeness of 99.0%. Repetitive sequences comprise 46.38% of the genome, with short interspersed nuclear elements (SINEs) accounting for the largest proportion. Additionally, we identified 24 centromeres and 46 telomeres. 32,298 protein-coding genes were annotated using de novo prediction and transcriptome data, functionally annotating 85% of them. This genome assembly provides genomic resources for studies on conservation, adaptive evolution and the exploration of genetic basis related to important traits of the Yarkand hare.
Additional Links: PMID-41680222
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@article {pmid41680222,
year = {2026},
author = {Xu, M and Cui, Y and Kuang, H and Wei, K and Shan, W},
title = {Telomere to telomere level genome assembly of the Yarkand hare (Lepus yarkandensis).},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06815-1},
pmid = {41680222},
issn = {2052-4463},
support = {32260116//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32260116//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32260116//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32260116//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {The Yarkand hare (Lepus yarkandensis) is endemic to the Tarim Basin in Xinjiang, China. It is a key species and a critical component of the Tarim Basin ecosystems. However, the lack of a reference genome has hindered evolutionary and genetic studies of this species. Here, we assembled a telomere-to-telomere (T2T) genome of the Yarkand hare (LepYark_1.0) using PacBio HiFi, Nanopore, and Hi-C sequencing. The assembled genome size is approximately 2.70 Gb, with a scaffold N50 of 126.86 Mb. About 94.88% of the assembled sequences could be anchored to 24 pseudo-chromosomes, with a BUSCO assessment indicating a completeness of 99.0%. Repetitive sequences comprise 46.38% of the genome, with short interspersed nuclear elements (SINEs) accounting for the largest proportion. Additionally, we identified 24 centromeres and 46 telomeres. 32,298 protein-coding genes were annotated using de novo prediction and transcriptome data, functionally annotating 85% of them. This genome assembly provides genomic resources for studies on conservation, adaptive evolution and the exploration of genetic basis related to important traits of the Yarkand hare.},
}
RevDate: 2026-02-12
Telomere length in patients with Marfan Syndrome.
International journal of cardiology pii:S0167-5273(26)00082-3 [Epub ahead of print].
BACKGROUND: Marfan syndrome (MFS) is a multisystemic heritable thoracic aortic disease entity characterized by progressive aortic dilatation and life-threatening cardiovascular complications. Chronic inflammation and oxidative stress are increasingly recognized in its pathophysiology, and are important drivers of telomere shortening, a hallmark of biological aging. We hypothesized that adults with MFS have shorter telomere length (TL) compared to healthy controls.
METHODS: Relative average leukocyte TL was measured in 59 adults with molecularly confirmed MFS (median age 38 years, 29 females) and 59 age- and sex-matched healthy controls. TL was determined by a singleplex qPCR assay.
RESULTS: Patients with MFS had shorter TL compared to healthy controls (0.99 ± 0.19 vs. 1.07 ± 0.21, p = 0.033). In univariate analysis, we found that major adverse cardiovascular events (defined as aortic dissection, arrhythmia or heart failure) were associated with shorter TL (β = -0.168, 95%CI -0.291; -0.013, p = 0.008). No other clinical or genetic variables showed significant associations in either the raw or age- and sex-adjusted TL analyses.
CONCLUSION: Adults with MFS have shorter leukocyte TL, and an association was found between shorter TL and severe cardiovascular events. These findings suggest a role for accelerated aging mechanisms in the pathophysiology of the disease.
Additional Links: PMID-41679654
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@article {pmid41679654,
year = {2026},
author = {Tournoy, TK and D'hulst, S and Demolder, A and Derudder, R and Martens, DS and Mosquera, LM and Coucke, P and De Backer, J},
title = {Telomere length in patients with Marfan Syndrome.},
journal = {International journal of cardiology},
volume = {},
number = {},
pages = {134234},
doi = {10.1016/j.ijcard.2026.134234},
pmid = {41679654},
issn = {1874-1754},
abstract = {BACKGROUND: Marfan syndrome (MFS) is a multisystemic heritable thoracic aortic disease entity characterized by progressive aortic dilatation and life-threatening cardiovascular complications. Chronic inflammation and oxidative stress are increasingly recognized in its pathophysiology, and are important drivers of telomere shortening, a hallmark of biological aging. We hypothesized that adults with MFS have shorter telomere length (TL) compared to healthy controls.
METHODS: Relative average leukocyte TL was measured in 59 adults with molecularly confirmed MFS (median age 38 years, 29 females) and 59 age- and sex-matched healthy controls. TL was determined by a singleplex qPCR assay.
RESULTS: Patients with MFS had shorter TL compared to healthy controls (0.99 ± 0.19 vs. 1.07 ± 0.21, p = 0.033). In univariate analysis, we found that major adverse cardiovascular events (defined as aortic dissection, arrhythmia or heart failure) were associated with shorter TL (β = -0.168, 95%CI -0.291; -0.013, p = 0.008). No other clinical or genetic variables showed significant associations in either the raw or age- and sex-adjusted TL analyses.
CONCLUSION: Adults with MFS have shorter leukocyte TL, and an association was found between shorter TL and severe cardiovascular events. These findings suggest a role for accelerated aging mechanisms in the pathophysiology of the disease.},
}
RevDate: 2026-02-12
Short telomeres in mitochondrial DNA depletion disorders.
Mitochondrion pii:S1567-7249(26)00021-8 [Epub ahead of print].
Mitochondrial DNA (mtDNA) depletion disorders (MDDs) are rare, genetically diverse conditions marked by a significant reduction in mtDNA, primarily affecting energy-demanding tissues such as muscle, liver, and brain, sometimes leading to catastrophic multisystem failure. In a cohort of patients with MDDs, we measured telomere length in lymphocytes, granulocytes, T cells, and B cells, and compared to healthy controls. Telomere length was shorter overall in patients with MDDs, with the most significant differences observed in granulocytes. The observation that mtDNA depletion is associated with shorter telomeres may provide insight into MDD pathophysiology. Telomere length may have potential as a biomarker in mitochondrial disease, but further study is needed.
Additional Links: PMID-41679577
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@article {pmid41679577,
year = {2026},
author = {Dille, Y and Rampakakis, E and Aubert, G and Dassi, C and Mannherz, W and Berrahmoune, S and Srour, M and Buhas, D and Agarwal, S and Myers, KA},
title = {Short telomeres in mitochondrial DNA depletion disorders.},
journal = {Mitochondrion},
volume = {},
number = {},
pages = {102131},
doi = {10.1016/j.mito.2026.102131},
pmid = {41679577},
issn = {1872-8278},
abstract = {Mitochondrial DNA (mtDNA) depletion disorders (MDDs) are rare, genetically diverse conditions marked by a significant reduction in mtDNA, primarily affecting energy-demanding tissues such as muscle, liver, and brain, sometimes leading to catastrophic multisystem failure. In a cohort of patients with MDDs, we measured telomere length in lymphocytes, granulocytes, T cells, and B cells, and compared to healthy controls. Telomere length was shorter overall in patients with MDDs, with the most significant differences observed in granulocytes. The observation that mtDNA depletion is associated with shorter telomeres may provide insight into MDD pathophysiology. Telomere length may have potential as a biomarker in mitochondrial disease, but further study is needed.},
}
RevDate: 2026-02-12
CmpDate: 2026-02-12
Reduced CHMP7 Expression Compromises Telomere Integrity in Mammalian Cells.
Cells, 15(3): pii:cells15030256.
During open mitosis, reassembly of the nuclear envelope requires the coordinated recruitment of the ESCRT machinery, initiated by the chromatin-associated factor BAF1 and the nuclear-envelope-associated factor LEM2. Because telomeres are enriched at the reforming envelope, we investigated whether ESCRT factors contribute to telomere integrity. Reduction in the pivotal nuclear ESCRT factor CHMP7 caused DNA damage, heterochromatin disorganization, and telomere defects, including sister telomere associations and telomere free ends. Extending this analysis, we found that additional ESCRT components, including TSG101, VPS28, CHMP4B, and the ESCRT-associated factor AKTIP/Ft1, also contribute to telomere integrity, although with different strengths. Genetic interaction analyses suggest that CHMP7 converges in a common pathway with CHMP4B and AKTIP/Ft1, while it functions in parallel routes to TNKS1, a telomere-specific regulator of the shelterin TRF1. More genetic analyses indicated that BAF1 and LEM2 contribute to safeguarding of telomeres during nuclear envelope reassembly. Because defects in nuclear envelope dynamics and chromatin-membrane coupling are hallmarks of disorders associated with nuclear deformation and fragility, including aging and cancer, our findings contribute a new angle into these conditions and suggest potential targets for selectively modulating telomere maintenance pathways.
Additional Links: PMID-41677621
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@article {pmid41677621,
year = {2026},
author = {Burla, R and La Torre, M and Maccaroni, K and Tacconi, S and Dini, L and Saggio, I},
title = {Reduced CHMP7 Expression Compromises Telomere Integrity in Mammalian Cells.},
journal = {Cells},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/cells15030256},
pmid = {41677621},
issn = {2073-4409},
support = {Award Number: Pro, Project code CN_00000033, Concession Decree No. 1034 of 17 June 2022//support of NBFC to IS, National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4-Call for tender No. 3138 of 16 December 2021, rectified by Decree n. 3175 of 18 December 2021 of Italian Ministry of University and Research funded b/ ; AIRC IG-24614 to IS//AIRC to IS/ ; Anna Tramontano call 2020//Istituto Pasteur Fondazione Cenci Bolognetti Anna Tramontano call 2020 to IS/ ; RP1201729E377B2D, RP11916B7F20A9E3, RP12218167BDB0A9//MUR-Sapienza to IS/ ; RM12117A5D970AB9 and GA122181AFEB4283//Sapienza to IS as co-PI/ ; AR22117A575BCFA5//Sapienza/ ; Programma di ricerca e formazione//Italian ministry of health 2022 Programma di ricerca e formazione to IS/ ; HLCA22Feb-0029//Singapore ministry of health to IS as co-PI/ ; },
mesh = {*Telomere/metabolism/genetics ; Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism/genetics ; Nuclear Envelope/metabolism ; Animals ; Heterochromatin/metabolism ; Nuclear Proteins/metabolism ; DNA Damage ; DNA-Binding Proteins/metabolism ; HeLa Cells ; },
abstract = {During open mitosis, reassembly of the nuclear envelope requires the coordinated recruitment of the ESCRT machinery, initiated by the chromatin-associated factor BAF1 and the nuclear-envelope-associated factor LEM2. Because telomeres are enriched at the reforming envelope, we investigated whether ESCRT factors contribute to telomere integrity. Reduction in the pivotal nuclear ESCRT factor CHMP7 caused DNA damage, heterochromatin disorganization, and telomere defects, including sister telomere associations and telomere free ends. Extending this analysis, we found that additional ESCRT components, including TSG101, VPS28, CHMP4B, and the ESCRT-associated factor AKTIP/Ft1, also contribute to telomere integrity, although with different strengths. Genetic interaction analyses suggest that CHMP7 converges in a common pathway with CHMP4B and AKTIP/Ft1, while it functions in parallel routes to TNKS1, a telomere-specific regulator of the shelterin TRF1. More genetic analyses indicated that BAF1 and LEM2 contribute to safeguarding of telomeres during nuclear envelope reassembly. Because defects in nuclear envelope dynamics and chromatin-membrane coupling are hallmarks of disorders associated with nuclear deformation and fragility, including aging and cancer, our findings contribute a new angle into these conditions and suggest potential targets for selectively modulating telomere maintenance pathways.},
}
MeSH Terms:
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*Telomere/metabolism/genetics
Humans
*Endosomal Sorting Complexes Required for Transport/metabolism/genetics
Nuclear Envelope/metabolism
Animals
Heterochromatin/metabolism
Nuclear Proteins/metabolism
DNA Damage
DNA-Binding Proteins/metabolism
HeLa Cells
RevDate: 2026-02-12
CmpDate: 2026-02-12
Plasma Proteome Signature for Leukocyte Telomere Length and Its Link to Abdominal Aortic Aneurysm.
Journal of cellular and molecular medicine, 30(3):e71047.
Shorter leukocyte telomere length (LTL) is an aging biomarker and risk factor for aging-related diseases, including abdominal aortic aneurysm (AAA). This study aimed to identify plasma proteins causally associated with LTL and investigate their roles in linking LTL to AAA. A proteomics analysis was conducted for LTL and a polygenic risk score (PRS) for LTL using 4955 plasma proteins by SomaScan in self-identified White participants (N = 7587-8055) from the Atherosclerosis Risk in Communities (ARIC) study. Replications were evaluated in self-identified Black participants (N = 1668-2094) from ARIC and White participants (N = 2333-2431) from the Cardiovascular Health Study (CHS). Mendelian randomization (MR) analysis assessed causality between LTL and proteins. Survival and mediation analyses explored protein-mediated associations between LTL and AAA risk. In ARIC White participants, 15 unique proteins were identified for LTL or LTL PRS. Three LTL-associated proteins (MZB1, PLOD3, COL28A1) replicated in ARIC Black participants, and six (TNFRSF17, MZB1, CHL1, GDF15, THPO and PLOD3) in CHS White participants. Three proteins associated with LTL PRS (THPO, GP1Bα, PEAR1) replicated in CHS White participants. MR analysis supported causal associations between LTL and five proteins (KDR, TNFRSF17, GDF15, ST3GAL6, CHL1) with all except GDF15 being novel to LTL. LTL was associated with AAA risk (HR = 0.873, 95% CI: 0.803-0.950), with GDF15 mediating 12.4% of this association (p = 0.028). We identified five proteins causally influenced by LTL and highlighted GDF15 as a mediator linking LTL to AAA risk, offering novel insights into aging biology and AAA pathogenesis.
Additional Links: PMID-41677031
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@article {pmid41677031,
year = {2026},
author = {Li, A and Austin, TR and Steffen, BT and Jacobson, I and Xie, J and Pankratz, N and Lane, JA and Fitzpatrick, A and Bis, JC and Arking, DE and Mosley, T and Sedaghat, S and Pankow, JS and Lutsey, PL and Guan, W and Tang, W},
title = {Plasma Proteome Signature for Leukocyte Telomere Length and Its Link to Abdominal Aortic Aneurysm.},
journal = {Journal of cellular and molecular medicine},
volume = {30},
number = {3},
pages = {e71047},
doi = {10.1111/jcmm.71047},
pmid = {41677031},
issn = {1582-4934},
support = {R21AG072530/AG/NIA NIH HHS/United States ; R01HL155209/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Aortic Aneurysm, Abdominal/blood/genetics/metabolism ; Male ; *Leukocytes/metabolism ; Female ; *Proteome/metabolism ; Middle Aged ; Biomarkers/blood ; Aged ; *Telomere/genetics/metabolism ; Mendelian Randomization Analysis ; Risk Factors ; *Telomere Homeostasis ; Proteomics/methods ; *Blood Proteins ; },
abstract = {Shorter leukocyte telomere length (LTL) is an aging biomarker and risk factor for aging-related diseases, including abdominal aortic aneurysm (AAA). This study aimed to identify plasma proteins causally associated with LTL and investigate their roles in linking LTL to AAA. A proteomics analysis was conducted for LTL and a polygenic risk score (PRS) for LTL using 4955 plasma proteins by SomaScan in self-identified White participants (N = 7587-8055) from the Atherosclerosis Risk in Communities (ARIC) study. Replications were evaluated in self-identified Black participants (N = 1668-2094) from ARIC and White participants (N = 2333-2431) from the Cardiovascular Health Study (CHS). Mendelian randomization (MR) analysis assessed causality between LTL and proteins. Survival and mediation analyses explored protein-mediated associations between LTL and AAA risk. In ARIC White participants, 15 unique proteins were identified for LTL or LTL PRS. Three LTL-associated proteins (MZB1, PLOD3, COL28A1) replicated in ARIC Black participants, and six (TNFRSF17, MZB1, CHL1, GDF15, THPO and PLOD3) in CHS White participants. Three proteins associated with LTL PRS (THPO, GP1Bα, PEAR1) replicated in CHS White participants. MR analysis supported causal associations between LTL and five proteins (KDR, TNFRSF17, GDF15, ST3GAL6, CHL1) with all except GDF15 being novel to LTL. LTL was associated with AAA risk (HR = 0.873, 95% CI: 0.803-0.950), with GDF15 mediating 12.4% of this association (p = 0.028). We identified five proteins causally influenced by LTL and highlighted GDF15 as a mediator linking LTL to AAA risk, offering novel insights into aging biology and AAA pathogenesis.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Aortic Aneurysm, Abdominal/blood/genetics/metabolism
Male
*Leukocytes/metabolism
Female
*Proteome/metabolism
Middle Aged
Biomarkers/blood
Aged
*Telomere/genetics/metabolism
Mendelian Randomization Analysis
Risk Factors
*Telomere Homeostasis
Proteomics/methods
*Blood Proteins
RevDate: 2026-02-12
CmpDate: 2026-02-12
Modeling telomere shortening process.
Quantitative biology (Beijing, China), 13(1):e74.
Cell senescence has attracted much attention in the long history of human beings, and telomere shortening (TS) is one of the main concerns in the study of cell senescence. To reveal the microscopic mechanism of TS process, we model it based on molecular stochastic process from the perspective of nonequilibrium statistical physics. We associate the TS process with the continuous time random walk and derive the Fokker-Planck equation to describe the length distribution of the TS. We further modify the model describing the TS process, similar to the anomalous tempered diffusion, and derive the Feynman-Kac equation characterizing the functional distribution of the TS process. Finally, we study the statistics related to the critical telomere length l c , including the occupation time and first passage time. These two kinds of statistics help us understand the time scale of cell senescence.
Additional Links: PMID-41675381
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@article {pmid41675381,
year = {2025},
author = {Han, P and Zhou, Y and Deng, W},
title = {Modeling telomere shortening process.},
journal = {Quantitative biology (Beijing, China)},
volume = {13},
number = {1},
pages = {e74},
pmid = {41675381},
issn = {2095-4697},
abstract = {Cell senescence has attracted much attention in the long history of human beings, and telomere shortening (TS) is one of the main concerns in the study of cell senescence. To reveal the microscopic mechanism of TS process, we model it based on molecular stochastic process from the perspective of nonequilibrium statistical physics. We associate the TS process with the continuous time random walk and derive the Fokker-Planck equation to describe the length distribution of the TS. We further modify the model describing the TS process, similar to the anomalous tempered diffusion, and derive the Feynman-Kac equation characterizing the functional distribution of the TS process. Finally, we study the statistics related to the critical telomere length l c , including the occupation time and first passage time. These two kinds of statistics help us understand the time scale of cell senescence.},
}
RevDate: 2026-02-11
A phased, near-telomere-to-telomere chromosome-scale reference genome of the Moroccan argan tree.
Scientific data pii:10.1038/s41597-026-06615-7 [Epub ahead of print].
The argan tree (Argania spinosa), endemic to Morocco, holds major ecological and economic value. We generated a high-quality, chromosome-scale, phased reference genome using PacBio HiFi long reads and Hi-C scaffolding. The assembly resolves two haplotypes, each organized into 11 pseudochromosomes (2n = 22). Haplotype-1 spans 621 Mb (scaffold N50 = 50 Mb; GC = 33.79%), and Haplotype-2 spans 615 Mb (scaffold N50 = 51 Mb; GC = 33.77%). BUSCO completeness is 97.8% for Hap1 and 98.1% for Hap2, with Merqury QV values of 75 for both, indicating high consensus accuracy and strong phasing. Telomeric repeats (AAACCCT)n appear at both ends of most chromosomes, and only small terminal gaps remain, so we conservatively classify the assemblies as near-T2T. We annotated 35,183 gene loci producing 39,805 mRNA isoforms and 410 tRNA genes, with 76.46% of loci functionally characterized. Repeats represent 61.65% of the genome, dominated by LTR retrotransposons. All raw data, assemblies, and annotations are publicly accessible, providing a robust genomic foundation for conservation genetics, breeding, and evolutionary studies in A. spinosa.
Additional Links: PMID-41673035
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@article {pmid41673035,
year = {2026},
author = {El Idrissi, H and Gkanogiannis, A and Iraqi, D and Khoulassa, S and Fokar, M and Badaoui, B and Moussadek, R and Mentag, R and Khayi, S},
title = {A phased, near-telomere-to-telomere chromosome-scale reference genome of the Moroccan argan tree.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06615-7},
pmid = {41673035},
issn = {2052-4463},
abstract = {The argan tree (Argania spinosa), endemic to Morocco, holds major ecological and economic value. We generated a high-quality, chromosome-scale, phased reference genome using PacBio HiFi long reads and Hi-C scaffolding. The assembly resolves two haplotypes, each organized into 11 pseudochromosomes (2n = 22). Haplotype-1 spans 621 Mb (scaffold N50 = 50 Mb; GC = 33.79%), and Haplotype-2 spans 615 Mb (scaffold N50 = 51 Mb; GC = 33.77%). BUSCO completeness is 97.8% for Hap1 and 98.1% for Hap2, with Merqury QV values of 75 for both, indicating high consensus accuracy and strong phasing. Telomeric repeats (AAACCCT)n appear at both ends of most chromosomes, and only small terminal gaps remain, so we conservatively classify the assemblies as near-T2T. We annotated 35,183 gene loci producing 39,805 mRNA isoforms and 410 tRNA genes, with 76.46% of loci functionally characterized. Repeats represent 61.65% of the genome, dominated by LTR retrotransposons. All raw data, assemblies, and annotations are publicly accessible, providing a robust genomic foundation for conservation genetics, breeding, and evolutionary studies in A. spinosa.},
}
RevDate: 2026-02-11
CmpDate: 2026-02-11
Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank.
Journal of neurology, 273(2):137.
BACKGROUND: This study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.
METHODS: Data from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.
RESULTS: Shorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40-0.67, P < 0.001), dementia in AD (HR: 0.53, 95% CI 0.39-0.73, P < 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58-0.95, P < 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45-0.84, P < 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48-0.82, P < 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38-0.55, P < 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91-7.18, P < 0.001). ML models confirmed the predictive value of LTL for NDDs.
CONCLUSION: Shorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.
Additional Links: PMID-41670794
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@article {pmid41670794,
year = {2026},
author = {Chen, X and Huang, Y and Zhao, C and Huang, M},
title = {Association between leukocyte telomere length and neurodegenerative diseases: a prospective cohort in the UK Biobank.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {137},
pmid = {41670794},
issn = {1432-1459},
support = {ZDXK202252//Jiangsu Provincial Medical Key Discipline/ ; K2023014//Jiangsu Provincial Health Commission Key Medical projects/ ; GSWS2022068//Suzhou Gusu Health Talent Plan Talent Research Project/ ; },
mesh = {Humans ; Male ; Female ; *Neurodegenerative Diseases/genetics/epidemiology ; United Kingdom/epidemiology ; *Leukocytes/metabolism ; Aged ; Biological Specimen Banks ; Middle Aged ; Prospective Studies ; *Telomere ; Cohort Studies ; Aged, 80 and over ; Machine Learning ; UK Biobank ; },
abstract = {BACKGROUND: This study aims to investigate the association between leukocyte telomere length (LTL) and the risk of incident NDDs using a large-scale cohort from the UK Biobank.
METHODS: Data from 459,902 subjects were analyzed using Cox proportional hazards models and machine learning (ML) algorithms to assess LTL's association with NDD risk.
RESULTS: Shorter LTL was associated with an increased risk of NDDs, including Alzheimer's disease (HR: 0.52, 95% CI 0.40-0.67, P < 0.001), dementia in AD (HR: 0.53, 95% CI 0.39-0.73, P < 0.001), unspecified dementia (HR: 0.74, 95% CI 0.58-0.95, P < 0.05), degenerative diseases of the nervous system (including other specified degenerative diseases such as circumscribed brain atrophy and senile degeneration of the brain) (HR: 0.62, 95% CI 0.45-0.84, P < 0.01), extrapyramidal and movement disorders (including other specified extrapyramidal and movement disorders such as a range of tremors, chorea, tics, and other abnormal involuntary movements) (HR: 0.63, 95% CI 0.48-0.82, P < 0.01), and mental and behavioral disorders due to use of alcohol (HR: 0.46, 95% CI 0.38-0.55, P < 0.001). Conversely, longer LTL was associated with a 3.71-fold increased risk of multiple sclerosis (MS) (HR: 3.71, 95% CI 1.91-7.18, P < 0.001). ML models confirmed the predictive value of LTL for NDDs.
CONCLUSION: Shorter LTL increased the risk of several NDDs, while longer LTL paradoxically predisposed individuals to MS, especially in younger populations. ML models demonstrated strong potential for predicting NDD risks, enhancing our understanding of the role of telomeres in neurodegeneration.},
}
MeSH Terms:
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Humans
Male
Female
*Neurodegenerative Diseases/genetics/epidemiology
United Kingdom/epidemiology
*Leukocytes/metabolism
Aged
Biological Specimen Banks
Middle Aged
Prospective Studies
*Telomere
Cohort Studies
Aged, 80 and over
Machine Learning
UK Biobank
RevDate: 2026-02-10
Relationship between genetically determined telomere length and childhood glioma risk.
Acta neuropathologica communications pii:10.1186/s40478-025-02199-2 [Epub ahead of print].
While longer genetically predicted leukocyte telomere length (LTL) has been linked to increased glioma risk in adults, this association has not been investigated in pediatric populations. In this study, we applied Mendelian randomization (MR) and polygenic risk score (PRS) analyses to investigate the relationship between LTL and pediatric glioma risk, using 4,069 cases and 8,778 controls from the largest available childhood glioma meta-GWAS. Results suggested longer genetically predicted LTL was significantly associated with increased childhood glioma risk, with OR per 1 standard deviation increase in LTL of 2.12 (95% CI 1.32-3.39, P = .002) in the multi-ancestry group and 2.16 (95% CI 1.16-4.03; P = .015) in the European group. Key SNPs contributing to risk of childhood glioma included rs59294613 (POT1), rs8105767 (ZNF208), and rs7705526 (TERT), which differed from the top variants previously identified in adult glioma using the same genetic instruments. Age-stratified MR revealed a stronger association in children diagnosed after the age of 6 (OR = 1.89; P < .001) vs. ≤ 6 years (OR = 1.04; P = .732; Phet = .006). PRS analysis further supported this age-stratified findings by demonstrating a positive association between LTL PRS and age at glioma diagnosis, particularly within age 0-10. This trend suggests a progressively greater influence of LTL on glioma risk in older children compared to younger children. In conclusion, this study provides the first genetic evidence linking longer genetically predicted LTL to increased pediatric glioma risk. While overall consistent with adult findings, distinct single-SNP associations, and age-dependent effects highlight unique biological mechanisms in children with glioma, warranting further direct investigation into telomere dynamics in early-life gliomagenesis.
Additional Links: PMID-41668119
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@article {pmid41668119,
year = {2026},
author = {Zhou, N and Li, S and Foss-Skiftesvik, J and Dahlin, AM and Bybjerg-Grauholm, J and Melin, B and de Smith, AJ and Walsh, KM and Wiemels, JL},
title = {Relationship between genetically determined telomere length and childhood glioma risk.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02199-2},
pmid = {41668119},
issn = {2051-5960},
support = {R01CA194189/CA/NCI NIH HHS/United States ; T33IR6502//Tobacco-Related Disease Research Program/ ; },
abstract = {While longer genetically predicted leukocyte telomere length (LTL) has been linked to increased glioma risk in adults, this association has not been investigated in pediatric populations. In this study, we applied Mendelian randomization (MR) and polygenic risk score (PRS) analyses to investigate the relationship between LTL and pediatric glioma risk, using 4,069 cases and 8,778 controls from the largest available childhood glioma meta-GWAS. Results suggested longer genetically predicted LTL was significantly associated with increased childhood glioma risk, with OR per 1 standard deviation increase in LTL of 2.12 (95% CI 1.32-3.39, P = .002) in the multi-ancestry group and 2.16 (95% CI 1.16-4.03; P = .015) in the European group. Key SNPs contributing to risk of childhood glioma included rs59294613 (POT1), rs8105767 (ZNF208), and rs7705526 (TERT), which differed from the top variants previously identified in adult glioma using the same genetic instruments. Age-stratified MR revealed a stronger association in children diagnosed after the age of 6 (OR = 1.89; P < .001) vs. ≤ 6 years (OR = 1.04; P = .732; Phet = .006). PRS analysis further supported this age-stratified findings by demonstrating a positive association between LTL PRS and age at glioma diagnosis, particularly within age 0-10. This trend suggests a progressively greater influence of LTL on glioma risk in older children compared to younger children. In conclusion, this study provides the first genetic evidence linking longer genetically predicted LTL to increased pediatric glioma risk. While overall consistent with adult findings, distinct single-SNP associations, and age-dependent effects highlight unique biological mechanisms in children with glioma, warranting further direct investigation into telomere dynamics in early-life gliomagenesis.},
}
RevDate: 2026-02-10
Telomere shortening in laminopathic dilated cardiomyopathy.
NPJ Regenerative medicine pii:10.1038/s41536-026-00462-1 [Epub ahead of print].
Laminopathies are a group of rare disease due to mutations in the LMNA gene, which is crucial for nuclear integrity and cellular rigidity. Depending on the mutation, the disease manifests in striated muscles, adipose tissues, nerves, and the heart. Although many laminopathic patients exhibit accelerated aging syndromes, the connection as to why loss of LMNA drives aging remains unknown. Herein, we present evidence that cardiomyocytes from laminopathic heart sections exhibit shortened telomeres. Patient derived hiPSC-CMs we observed LMNA mutation results in myocardial enlargement and altered contractility in cardiomyocytes. Further, laminopathic murine cardiomyocytes recapitulates telomere attrition phenotype.
Additional Links: PMID-41667453
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@article {pmid41667453,
year = {2026},
author = {Chang, ACY and Pardon, G and Chang, ACH and Wang, C and Termglinchan, V and Kirillova, A and Nicin, L and Birnbaum, F and Laquerrière, A and Bonne, G and Wu, J and Blau, HM},
title = {Telomere shortening in laminopathic dilated cardiomyopathy.},
journal = {NPJ Regenerative medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41536-026-00462-1},
pmid = {41667453},
issn = {2057-3995},
support = {82070248//National Natural Science Foundation of China/ ; 19PJ1407000//Shanghai Pujiang Program/ ; 0900000024//Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning/ ; 13POST14480004//American Heart Association/ ; 17MERIT33610009//American Heart Association/ ; 17CSA33590101//American Heart Association/ ; 18POST34080160//American Heart Association, United States/ ; #P2SKP2_164954//Swiss National Science Foundation (SNSF) Early Postdoc Mobility Fellowship/ ; R01 AG044815/NH/NIH HHS/United States ; },
abstract = {Laminopathies are a group of rare disease due to mutations in the LMNA gene, which is crucial for nuclear integrity and cellular rigidity. Depending on the mutation, the disease manifests in striated muscles, adipose tissues, nerves, and the heart. Although many laminopathic patients exhibit accelerated aging syndromes, the connection as to why loss of LMNA drives aging remains unknown. Herein, we present evidence that cardiomyocytes from laminopathic heart sections exhibit shortened telomeres. Patient derived hiPSC-CMs we observed LMNA mutation results in myocardial enlargement and altered contractility in cardiomyocytes. Further, laminopathic murine cardiomyocytes recapitulates telomere attrition phenotype.},
}
RevDate: 2026-02-10
Photoprotection from UV light-induced telomere shortening and DNA damage by a broad-spectrum sunscreen.
Journal of photochemistry and photobiology. B, Biology, 276:113375 pii:S1011-1344(26)00022-9 [Epub ahead of print].
BACKGROUND: Ultraviolet (UV) radiation contributes to photoaging and skin cancer by causing DNA damage and generating reactive oxygen species (ROS). It also induces telomere shortening, a key factor in cellular aging. However, no studies have investigated whether sunscreen can prevent short-term telomere shortening caused by UV exposure to human skin.
OBJECTIVES: We have examined whether the use of a broad-spectrum sunscreen product can protect at the telomere level from the harmful effects of UV light.
METHODS: Human keratinocytes and a 3D skin model were exposed to 10 J/cm[2] of solar-simulated UV radiation under three conditions: non-exposed, exposed, and exposed with broad-spectrum sunscreen. DNA damage, assessed by γH2AX levels, was measured at 30 min and 24 h post-irradiation. Telomere length was evaluated by high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at 24 h post-irradiation. Histological analysis of 3D skin samples was performed using hematoxylin and eosin (H&E) staining to assess tissue integrity.
RESULTS: A decrease in cell number, increased DNA damage, and telomere shortening, accompanied by a higher proportion of critically short telomeres, were observed in UV-exposed keratinocytes and reconstructed human skin following exposure to 10 J/cm[2] of solar-simulated UV radiation. The 3D skin architecture was also compromised, showing loss of keratinocytes spatial organization, evidence of epidermal cell death, and significant dermal thinning. However, cells and 3D skin samples protected with a broad-spectrum sunscreen remained comparable to non-exposed controls, showing no detectable structural or molecular alterations.
CONCLUSIONS: These findings provide initial evidence that a broad-spectrum sunscreen product can mitigate UV-induced telomere shortening and DNA double-strand damage (DSBs), thereby preventing photodamage associated with solar exposure.
Additional Links: PMID-41666530
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@article {pmid41666530,
year = {2026},
author = {Hernández-Silva, D and Matabuena, M and Guío-Carrión, A and Aguilera, J and Martín, A and Megias, D and Mínguez, D and Demessant-Flavigny, AL and Castillejo, I and Bernerd, F and Prieto, L and Blasco, MA},
title = {Photoprotection from UV light-induced telomere shortening and DNA damage by a broad-spectrum sunscreen.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {276},
number = {},
pages = {113375},
doi = {10.1016/j.jphotobiol.2026.113375},
pmid = {41666530},
issn = {1873-2682},
abstract = {BACKGROUND: Ultraviolet (UV) radiation contributes to photoaging and skin cancer by causing DNA damage and generating reactive oxygen species (ROS). It also induces telomere shortening, a key factor in cellular aging. However, no studies have investigated whether sunscreen can prevent short-term telomere shortening caused by UV exposure to human skin.
OBJECTIVES: We have examined whether the use of a broad-spectrum sunscreen product can protect at the telomere level from the harmful effects of UV light.
METHODS: Human keratinocytes and a 3D skin model were exposed to 10 J/cm[2] of solar-simulated UV radiation under three conditions: non-exposed, exposed, and exposed with broad-spectrum sunscreen. DNA damage, assessed by γH2AX levels, was measured at 30 min and 24 h post-irradiation. Telomere length was evaluated by high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at 24 h post-irradiation. Histological analysis of 3D skin samples was performed using hematoxylin and eosin (H&E) staining to assess tissue integrity.
RESULTS: A decrease in cell number, increased DNA damage, and telomere shortening, accompanied by a higher proportion of critically short telomeres, were observed in UV-exposed keratinocytes and reconstructed human skin following exposure to 10 J/cm[2] of solar-simulated UV radiation. The 3D skin architecture was also compromised, showing loss of keratinocytes spatial organization, evidence of epidermal cell death, and significant dermal thinning. However, cells and 3D skin samples protected with a broad-spectrum sunscreen remained comparable to non-exposed controls, showing no detectable structural or molecular alterations.
CONCLUSIONS: These findings provide initial evidence that a broad-spectrum sunscreen product can mitigate UV-induced telomere shortening and DNA double-strand damage (DSBs), thereby preventing photodamage associated with solar exposure.},
}
RevDate: 2026-02-10
Relative Telomere Length in Leukocytes as a Potential Biomarker of Male Idiopathic Infertility.
Bulletin of experimental biology and medicine [Epub ahead of print].
The relative length of telomeric repeats in peripheral blood leukocytes was assessed in men with idiopathic infertility. A retrospective analysis was conducted on data from men in infertile couples, and a subgroup diagnosed with idiopathic infertility was identified. A control group of apparently healthy fertile men with proven reproductive function was also established. Genomic DNA was extracted from whole venous blood samples. Men with idiopathic infertility exhibited a significantly shorter relative telomere length reduced by approximately 40% in comparison with fertile controls (p < 0.05). This telomere shortening suggests ongoing genomic instability, likely driven by oxidative stress-mediated DNA damage. Although telomere length is emerging as a potential biomarker of male reproductive health, current evidence regarding its role in idiopathic infertility remains limited. The findings presented here highlight the need for further research to elucidate the molecular mechanisms governing telomere dynamics in the context of male infertility.
Additional Links: PMID-41665749
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@article {pmid41665749,
year = {2026},
author = {Kurashova, NA and Dashiev, BG and Kolesnikov, SI and Kolesnikova, LI},
title = {Relative Telomere Length in Leukocytes as a Potential Biomarker of Male Idiopathic Infertility.},
journal = {Bulletin of experimental biology and medicine},
volume = {},
number = {},
pages = {},
pmid = {41665749},
issn = {1573-8221},
abstract = {The relative length of telomeric repeats in peripheral blood leukocytes was assessed in men with idiopathic infertility. A retrospective analysis was conducted on data from men in infertile couples, and a subgroup diagnosed with idiopathic infertility was identified. A control group of apparently healthy fertile men with proven reproductive function was also established. Genomic DNA was extracted from whole venous blood samples. Men with idiopathic infertility exhibited a significantly shorter relative telomere length reduced by approximately 40% in comparison with fertile controls (p < 0.05). This telomere shortening suggests ongoing genomic instability, likely driven by oxidative stress-mediated DNA damage. Although telomere length is emerging as a potential biomarker of male reproductive health, current evidence regarding its role in idiopathic infertility remains limited. The findings presented here highlight the need for further research to elucidate the molecular mechanisms governing telomere dynamics in the context of male infertility.},
}
RevDate: 2026-02-10
Effects of intergenerational parent-child separation on early eruption of permanent molar and telomere length: a cross-sectional study among Chinese children aged 3-6 years.
BMC oral health pii:10.1186/s12903-026-07865-y [Epub ahead of print].
Additional Links: PMID-41664073
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@article {pmid41664073,
year = {2026},
author = {Yu, X and Zhang, Y and Lu, X and Ma, K and Sun, Y and Chen, X},
title = {Effects of intergenerational parent-child separation on early eruption of permanent molar and telomere length: a cross-sectional study among Chinese children aged 3-6 years.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-026-07865-y},
pmid = {41664073},
issn = {1472-6831},
support = {82173537//National Natural Science Foundation of China/ ; },
}
RevDate: 2026-02-09
Telomeres and Telomerase.
Telomeres represent a molecular nexus where genome stability, aging, disease susceptibility, and regenerative potential converge. Advances in understanding how telomeres are replicated, protected, and repaired now inform fundamental questions about human lifespan, tissue renewal, the molecular origins of age-related decline, and cancer evolution. This volume presents an integrated collection of perspectives spanning telomere architecture, replication dynamics, telomere-driven genome instability, and telomere maintenance by telomerase and Alternative Lengthening of Telomeres (ALT), while also charting new therapeutic directions grounded in telomere biology. Drawing on molecular, structural, organismal, and clinical research, this collection showcases a field in rapid motion, reshaping our view of regeneration, aging, and disease.
Additional Links: PMID-41663282
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@article {pmid41663282,
year = {2026},
author = {Cooper, JP and Denchi, EL and Lingner, J and Pickett, HA},
title = {Telomeres and Telomerase.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041972},
pmid = {41663282},
issn = {1943-0264},
abstract = {Telomeres represent a molecular nexus where genome stability, aging, disease susceptibility, and regenerative potential converge. Advances in understanding how telomeres are replicated, protected, and repaired now inform fundamental questions about human lifespan, tissue renewal, the molecular origins of age-related decline, and cancer evolution. This volume presents an integrated collection of perspectives spanning telomere architecture, replication dynamics, telomere-driven genome instability, and telomere maintenance by telomerase and Alternative Lengthening of Telomeres (ALT), while also charting new therapeutic directions grounded in telomere biology. Drawing on molecular, structural, organismal, and clinical research, this collection showcases a field in rapid motion, reshaping our view of regeneration, aging, and disease.},
}
RevDate: 2026-02-09
Metformin exhibits gender specific impact on telomere dynamics by enhancing RAP1 expression in type-2 diabetes mellitus.
Acta diabetologica [Epub ahead of print].
Telomere length serves as a critical biomarker of ageing, and diabetes is associated with shorter telomeres. This study aims to investigate the association and underlying molecular mechanism between telomere attrition rate in healthy individuals and patients with type 2 diabetes who consume the anti-diabetic drug metformin. Leukocyte telomere length was measured using the telomere restriction fragment assay in 111 healthy individuals and in 73 individuals with type 2 diabetes who were consuming metformin. Telomere length-regulating mRNA and protein expression studies were performed. The BJ fibroblast cell line was treated with different concentrations of metformin, and telomere length analysis, gene expression and chromatin immunoprecipitation (ChIP) were performed. Compared to healthy volunteers, telomere attrition was markedly reduced in diabetic patients who were on metformin. Diabetic females, in particular, showed an increase in telomere length, while males showed a reduction in the telomere attrition rate. In the BJ fibroblasts, metformin slowed telomere attrition in a dose-dependent manner. Molecular studies revealed that metformin treatment resulted in increased expression of telomeric protein RAP1 via enhanced PGC1α-dependent Foxo3a recruitment to the RAP1 promoter. Metformin is associated with decreased telomere attrition and increased telomeric protein RAP1 expression in both diabetic patients and in the fibroblast model. The effect is particularly significant in females. To our knowledge, this is the first study to identify a PGC-1α-FOXO3a-RAP1 signaling axis linking metformin exposure to telomere protection in human diabetic cohorts and to mechanistically validate this pathway using a fibroblast model.
Additional Links: PMID-41661273
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@article {pmid41661273,
year = {2026},
author = {Jain, M and Madeka, S and Khattar, E},
title = {Metformin exhibits gender specific impact on telomere dynamics by enhancing RAP1 expression in type-2 diabetes mellitus.},
journal = {Acta diabetologica},
volume = {},
number = {},
pages = {},
pmid = {41661273},
issn = {1432-5233},
support = {IO403061//SVKM's NMIMS Deemed to be University/ ; },
abstract = {Telomere length serves as a critical biomarker of ageing, and diabetes is associated with shorter telomeres. This study aims to investigate the association and underlying molecular mechanism between telomere attrition rate in healthy individuals and patients with type 2 diabetes who consume the anti-diabetic drug metformin. Leukocyte telomere length was measured using the telomere restriction fragment assay in 111 healthy individuals and in 73 individuals with type 2 diabetes who were consuming metformin. Telomere length-regulating mRNA and protein expression studies were performed. The BJ fibroblast cell line was treated with different concentrations of metformin, and telomere length analysis, gene expression and chromatin immunoprecipitation (ChIP) were performed. Compared to healthy volunteers, telomere attrition was markedly reduced in diabetic patients who were on metformin. Diabetic females, in particular, showed an increase in telomere length, while males showed a reduction in the telomere attrition rate. In the BJ fibroblasts, metformin slowed telomere attrition in a dose-dependent manner. Molecular studies revealed that metformin treatment resulted in increased expression of telomeric protein RAP1 via enhanced PGC1α-dependent Foxo3a recruitment to the RAP1 promoter. Metformin is associated with decreased telomere attrition and increased telomeric protein RAP1 expression in both diabetic patients and in the fibroblast model. The effect is particularly significant in females. To our knowledge, this is the first study to identify a PGC-1α-FOXO3a-RAP1 signaling axis linking metformin exposure to telomere protection in human diabetic cohorts and to mechanistically validate this pathway using a fibroblast model.},
}
RevDate: 2026-02-08
Unsuppressed viraemia and lower CD4 count associated with faster telomere attrition in African children with perinatal HIV on long-term antiretroviral therapy.
The Journal of infectious diseases pii:8467185 [Epub ahead of print].
BACKGROUND: HIV leads to reduced telomere length (TL), a biomarker of immune ageing. We investigated relationships between HIV viral load (VL) and CD4 count with TL and its rate of attrition in children with HIV (CWH) from Zambia and Zimbabwe.
METHODS: Buffy coat was obtained at baseline and 48 weeks from children aged 11-19 years with perinatally-acquired HIV taking combination antiretroviral therapy (cART) for >6 months recruited into the VITALITY trial [Trial registration no: PACTR202009897660297]. Relative TL was measured using monochrome multiplex qPCR, standardising units for analysis. Cross-sectional analyses used multivariable linear regression adjusting for age, sex and study site; longitudinal analysis additionally adjusted for baseline TL.
RESULTS: Among participants at baseline (N=842, mean±SD age 15.5±2.6 years, 53.2% female), 678(80.5%) had HIV VL<60 copies/mL, 66(7.8%) had 60-1000 copies/mL and 98(11.6%) had >1000 copies/mL. The CD4 count was 584±243 cells/μL. Compared to participants with VL<60 copies/mL, those with VL>1000 copies/mL had shorter TL (β[95%CI]=-0.239[-0.451, -0.026], P=0.028) whereas those with 60-1000 copies/mL did not (P=0.836). Lower CD4 cell count was associated with shorter TL (β[95%CI]=-0.038[-0.009, -0.066] per 100 CD4 cells/μL, P=0.009). In longitudinal analysis (N=783) after 336±6 days, those with HIV VL>1000 copies/mL at both timepoints had an accelerated telomere attrition rate (β[95%CI]=-0.276[-0.546, -0.005], P=0.046) compared with participants with VL<1000 copies/mL. Lower baseline CD4 count was associated with faster telomere attrition rate (β[95%CI]=-0.033[-0.008, -0.057], P=0.009).
CONCLUSIONS: HIV VL>1000 copies/mL among CWH on cART in Africa is associated with a degradation of immune age within one year, which may increase risk of co-morbidities later in life.
Additional Links: PMID-41655979
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@article {pmid41655979,
year = {2026},
author = {Shellard, JPG and Carr, E and Tam-McMillan, G and Mao, EW and Mujuru, H and Banda Mabuda, H and Chisenga, M and Bandason, T and Dzavakwa, NV and Kasonka, L and Simms, V and Gregson, CL and Ferrand, RA and Rowland-Jones, SL and Hsieh, AYY},
title = {Unsuppressed viraemia and lower CD4 count associated with faster telomere attrition in African children with perinatal HIV on long-term antiretroviral therapy.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag060},
pmid = {41655979},
issn = {1537-6613},
abstract = {BACKGROUND: HIV leads to reduced telomere length (TL), a biomarker of immune ageing. We investigated relationships between HIV viral load (VL) and CD4 count with TL and its rate of attrition in children with HIV (CWH) from Zambia and Zimbabwe.
METHODS: Buffy coat was obtained at baseline and 48 weeks from children aged 11-19 years with perinatally-acquired HIV taking combination antiretroviral therapy (cART) for >6 months recruited into the VITALITY trial [Trial registration no: PACTR202009897660297]. Relative TL was measured using monochrome multiplex qPCR, standardising units for analysis. Cross-sectional analyses used multivariable linear regression adjusting for age, sex and study site; longitudinal analysis additionally adjusted for baseline TL.
RESULTS: Among participants at baseline (N=842, mean±SD age 15.5±2.6 years, 53.2% female), 678(80.5%) had HIV VL<60 copies/mL, 66(7.8%) had 60-1000 copies/mL and 98(11.6%) had >1000 copies/mL. The CD4 count was 584±243 cells/μL. Compared to participants with VL<60 copies/mL, those with VL>1000 copies/mL had shorter TL (β[95%CI]=-0.239[-0.451, -0.026], P=0.028) whereas those with 60-1000 copies/mL did not (P=0.836). Lower CD4 cell count was associated with shorter TL (β[95%CI]=-0.038[-0.009, -0.066] per 100 CD4 cells/μL, P=0.009). In longitudinal analysis (N=783) after 336±6 days, those with HIV VL>1000 copies/mL at both timepoints had an accelerated telomere attrition rate (β[95%CI]=-0.276[-0.546, -0.005], P=0.046) compared with participants with VL<1000 copies/mL. Lower baseline CD4 count was associated with faster telomere attrition rate (β[95%CI]=-0.033[-0.008, -0.057], P=0.009).
CONCLUSIONS: HIV VL>1000 copies/mL among CWH on cART in Africa is associated with a degradation of immune age within one year, which may increase risk of co-morbidities later in life.},
}
RevDate: 2026-02-07
Long-Read Amplicon Sequencing for the Detection of TERT Promoter Variant Clonal Hematopoiesis in Patients with Telomere Biology Disorders.
The Journal of molecular diagnostics : JMD pii:S1525-1578(26)00019-X [Epub ahead of print].
Acquired TERT promoter (TERTp) variants are found in the blood of patients with telomere biology disorders (TBDs) and carry diagnostic and prognostic significance. Detection of these variants is challenging due to low variant allele frequencies (VAFs) and high GC content. We tested the sensitivity of long-read amplicon sequencing with deepSNV analysis, referred to as LR-deep AmpSeq, for TERTp variant detection. Among 47 patients with TBD features, we achieved an average depth of coverage of 7,943x and detected seven TERTp variants in six individuals (13%) with VAFs ranging from 0.006-0.33. Our results demonstrate that LR-deep AmpSeq is a sensitive, cost-effective method to detect low VAF TERTp variants.
Additional Links: PMID-41654254
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@article {pmid41654254,
year = {2026},
author = {Kirchner, R and Pereira, M and Peterson, M and Berres, ME and Churpek, JE},
title = {Long-Read Amplicon Sequencing for the Detection of TERT Promoter Variant Clonal Hematopoiesis in Patients with Telomere Biology Disorders.},
journal = {The Journal of molecular diagnostics : JMD},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmoldx.2026.01.005},
pmid = {41654254},
issn = {1943-7811},
abstract = {Acquired TERT promoter (TERTp) variants are found in the blood of patients with telomere biology disorders (TBDs) and carry diagnostic and prognostic significance. Detection of these variants is challenging due to low variant allele frequencies (VAFs) and high GC content. We tested the sensitivity of long-read amplicon sequencing with deepSNV analysis, referred to as LR-deep AmpSeq, for TERTp variant detection. Among 47 patients with TBD features, we achieved an average depth of coverage of 7,943x and detected seven TERTp variants in six individuals (13%) with VAFs ranging from 0.006-0.33. Our results demonstrate that LR-deep AmpSeq is a sensitive, cost-effective method to detect low VAF TERTp variants.},
}
RevDate: 2026-02-06
CmpDate: 2026-02-06
The association of serum levels of vitamin D with leucocyte telomere length, as a marker of biological aging: A meta-analysis.
Medicine, 105(6):e44487.
BACKGROUND: Short telomere length (TL) has been associated with chronic diseases and reduced lifespan. Vitamin D may help preserve telomeres through its anti-inflammatory effects; however, the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and TL remains inconclusive. This meta-analysis was conducted to evaluate the association between circulating 25(OH)D and leukocyte TL (LTL).
METHODS: A comprehensive literature search was performed across PubMed, Scopus, Google Scholar, ClinicalTrials.gov, and Cochrane Library to identify relevant studies published up to February 2025. Standardized β coefficients with 95% confidence intervals were applied as the effect size metric to evaluate the associations using a random effect model.
RESULTS: A total of 21 studies comprising 185,191 participants were analyzed. The overall results demonstrated a positive association between serum 25(OH)D levels and LTL (β = 0.04, 95% CI = 0.02-0.06), with remarkable heterogeneity across studies (I²= 89.1%, P ≤.001). This association was supported in adults (β = 0.04, 95% CI = 0.03-0.06), women (β = 0.05, 95% CI = 0.01-0.08), individuals with vitamin D deficiency (β = 0.22, 95% CI = 0.01-0.43), and studies that adjusted for covariates (β = 0.05, 95% CI = 0.01-0.08). No significant associations were found in men, participants with serum 25(OH)D levels ≥ 30 ng/mL, children, or studies without covariate adjustments. The relationships were not influenced by the method of TL assessment, body mass index, smoking status, and sample size.
CONCLUSION: Serum 25(OH)D levels showed a positive correlation with LTL in women, adults, and individuals with vitamin D deficiency.
Additional Links: PMID-41650046
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@article {pmid41650046,
year = {2026},
author = {Shen, J and Wang, L and Liu, J and Fan, Z and Li, G},
title = {The association of serum levels of vitamin D with leucocyte telomere length, as a marker of biological aging: A meta-analysis.},
journal = {Medicine},
volume = {105},
number = {6},
pages = {e44487},
doi = {10.1097/MD.0000000000044487},
pmid = {41650046},
issn = {1536-5964},
mesh = {Humans ; *Vitamin D/blood/analogs & derivatives ; *Leukocytes/metabolism ; *Aging/blood/genetics ; Vitamin D Deficiency/blood ; Biomarkers/blood ; Female ; *Telomere ; Male ; Adult ; },
abstract = {BACKGROUND: Short telomere length (TL) has been associated with chronic diseases and reduced lifespan. Vitamin D may help preserve telomeres through its anti-inflammatory effects; however, the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and TL remains inconclusive. This meta-analysis was conducted to evaluate the association between circulating 25(OH)D and leukocyte TL (LTL).
METHODS: A comprehensive literature search was performed across PubMed, Scopus, Google Scholar, ClinicalTrials.gov, and Cochrane Library to identify relevant studies published up to February 2025. Standardized β coefficients with 95% confidence intervals were applied as the effect size metric to evaluate the associations using a random effect model.
RESULTS: A total of 21 studies comprising 185,191 participants were analyzed. The overall results demonstrated a positive association between serum 25(OH)D levels and LTL (β = 0.04, 95% CI = 0.02-0.06), with remarkable heterogeneity across studies (I²= 89.1%, P ≤.001). This association was supported in adults (β = 0.04, 95% CI = 0.03-0.06), women (β = 0.05, 95% CI = 0.01-0.08), individuals with vitamin D deficiency (β = 0.22, 95% CI = 0.01-0.43), and studies that adjusted for covariates (β = 0.05, 95% CI = 0.01-0.08). No significant associations were found in men, participants with serum 25(OH)D levels ≥ 30 ng/mL, children, or studies without covariate adjustments. The relationships were not influenced by the method of TL assessment, body mass index, smoking status, and sample size.
CONCLUSION: Serum 25(OH)D levels showed a positive correlation with LTL in women, adults, and individuals with vitamin D deficiency.},
}
MeSH Terms:
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Humans
*Vitamin D/blood/analogs & derivatives
*Leukocytes/metabolism
*Aging/blood/genetics
Vitamin D Deficiency/blood
Biomarkers/blood
Female
*Telomere
Male
Adult
RevDate: 2026-02-06
Telomere-to-telomere assembly detects genomic diversity in Canadian strains of Borrelia burgdorferi.
Cell reports, 45(2):116935 pii:S2211-1247(26)00013-6 [Epub ahead of print].
Borrelia burgdorferi, the bacteria causing Lyme disease, has a complex genome comprising a linear chromosome and multiple linear and circular plasmids. The atypical hairpin telomeres and the highly paralogous plasmids complicate genome assembly. We develop a genome assembly pipeline using both long and short reads to overcome these challenges. Using long reads, we assemble the hairpin telomeres of the linear replicons, an lp28-1a plasmid subtype, and circular plasmids of nine B. burgdorferi strains from five regions across Northwest Ontario and Manitoba, Canada. Although similar across the core conserved genomic regions, all strains carry a ∼2-10 kb right telomeric end identical to lp28-1, leading to variability in telomere length and gene content. Additionally, we observe diversity at the linear chromosome hairpin telomeric sequences, ospC types, and plasmid profiles, highlighting the genomic diversity among the geographically proximate strains and suggesting such variations as possible mechanisms of rapid evolution.
Additional Links: PMID-41649924
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@article {pmid41649924,
year = {2026},
author = {Amin, AB and Ibarra-Meneses, AV and Gagnon, S and Merhi, G and Olivier, M and Ndao, M and Blanchette, M and Fernandez-Prada, C and Langlais, D},
title = {Telomere-to-telomere assembly detects genomic diversity in Canadian strains of Borrelia burgdorferi.},
journal = {Cell reports},
volume = {45},
number = {2},
pages = {116935},
doi = {10.1016/j.celrep.2026.116935},
pmid = {41649924},
issn = {2211-1247},
abstract = {Borrelia burgdorferi, the bacteria causing Lyme disease, has a complex genome comprising a linear chromosome and multiple linear and circular plasmids. The atypical hairpin telomeres and the highly paralogous plasmids complicate genome assembly. We develop a genome assembly pipeline using both long and short reads to overcome these challenges. Using long reads, we assemble the hairpin telomeres of the linear replicons, an lp28-1a plasmid subtype, and circular plasmids of nine B. burgdorferi strains from five regions across Northwest Ontario and Manitoba, Canada. Although similar across the core conserved genomic regions, all strains carry a ∼2-10 kb right telomeric end identical to lp28-1, leading to variability in telomere length and gene content. Additionally, we observe diversity at the linear chromosome hairpin telomeric sequences, ospC types, and plasmid profiles, highlighting the genomic diversity among the geographically proximate strains and suggesting such variations as possible mechanisms of rapid evolution.},
}
RevDate: 2026-02-06
CmpDate: 2026-02-06
The effect of training and Tribulus terrestris extract on the antioxidant system and telomere functional markers in the liver tissue of rats exposed to stanozolol.
Avicenna journal of phytomedicine, 16(1):184-194.
OBJECTIVE: The present study aimed to assess the effect of training along with administration of Tribulus terrestris (T) on the antioxidant system and telomere functional markers in the liver tissue of rats exposed to stanozolol.
MATERIALS AND METHODS: Forty- nine male rats, with average age and weight of 8-10 weeks and 180-220 g respectively, were randomly divided into 7 groups of seven rats: 1) Sh: Sham, 2) S: stanozolol, 3) S+T50: stanozolol+ 50 mg/kg T. terrestris, 4) S+T100: stanozolol+ 100 mg/kg T. terrestris, 5) S+RT: stanozolol + resistance training, 6) S+RT+T50: stanozolol + resistance training + 50 mg/kg T. terrestris, and 7) S+RT+T100: stanozolol + resistance training + 100 mg/kg T. terrestris. Rats in the S groups received 5 mg/kg stanozolol intraperitoneally (25 mg/kg/wk). Groups 5 (R+T), 6 (S+RT+T50), and 7 (S+RT+T100) performed resistance trainings three sessions per week with an intensity of 30-100 percent of body weight for eight weeks. Also, groups 3 (S+T50), 4 (S+T100), 6 (S+RT+T50) and 7 (S+RT+T100) received daily ethanolic extract of T with doses of 50 and 100 mg/kg intraperitoneally.
RESULTS: In the S+RT, S+T50, S+T100, S+RT+T50, and S+RT+T100 groups, malondialdehyde (MDA) levels were significantly lower and gene expression of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), and telomerase reverse transcriptase (TERT) levels were higher than the S group. Also, phosphatase and tensin homolog (PTEN) and TERT gene expression levels in the S+T100 group were significantly higher than the S+T50 group.
CONCLUSION: Training and T have a positive effect on the transcription pathway of antioxidants and telomere protection.
Additional Links: PMID-41647456
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@article {pmid41647456,
year = {2026},
author = {Kiani, N and Keshavarz, S and Hosseini, SA and Banai, J},
title = {The effect of training and Tribulus terrestris extract on the antioxidant system and telomere functional markers in the liver tissue of rats exposed to stanozolol.},
journal = {Avicenna journal of phytomedicine},
volume = {16},
number = {1},
pages = {184-194},
pmid = {41647456},
issn = {2228-7930},
abstract = {OBJECTIVE: The present study aimed to assess the effect of training along with administration of Tribulus terrestris (T) on the antioxidant system and telomere functional markers in the liver tissue of rats exposed to stanozolol.
MATERIALS AND METHODS: Forty- nine male rats, with average age and weight of 8-10 weeks and 180-220 g respectively, were randomly divided into 7 groups of seven rats: 1) Sh: Sham, 2) S: stanozolol, 3) S+T50: stanozolol+ 50 mg/kg T. terrestris, 4) S+T100: stanozolol+ 100 mg/kg T. terrestris, 5) S+RT: stanozolol + resistance training, 6) S+RT+T50: stanozolol + resistance training + 50 mg/kg T. terrestris, and 7) S+RT+T100: stanozolol + resistance training + 100 mg/kg T. terrestris. Rats in the S groups received 5 mg/kg stanozolol intraperitoneally (25 mg/kg/wk). Groups 5 (R+T), 6 (S+RT+T50), and 7 (S+RT+T100) performed resistance trainings three sessions per week with an intensity of 30-100 percent of body weight for eight weeks. Also, groups 3 (S+T50), 4 (S+T100), 6 (S+RT+T50) and 7 (S+RT+T100) received daily ethanolic extract of T with doses of 50 and 100 mg/kg intraperitoneally.
RESULTS: In the S+RT, S+T50, S+T100, S+RT+T50, and S+RT+T100 groups, malondialdehyde (MDA) levels were significantly lower and gene expression of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), and telomerase reverse transcriptase (TERT) levels were higher than the S group. Also, phosphatase and tensin homolog (PTEN) and TERT gene expression levels in the S+T100 group were significantly higher than the S+T50 group.
CONCLUSION: Training and T have a positive effect on the transcription pathway of antioxidants and telomere protection.},
}
RevDate: 2026-02-05
Time-Efficient and Informatic-Skill-Light Gap-Filling for Telomere-to-Telomere Genome Assembly.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].
Despite remarkable advances in sequencing technologies and automated genome assembly algorithms, manual gap-filling remains indispensable for achieving telomere-to-telomere (T2T) genome assemblies, a process that can take weeks or even months. Additionally, these tasks require advanced bioinformatics expertise, thereby excluding many biologists from direct participation in T2T genome projects. This severely restricts the ability to construct T2T genomes for larger populations and a wider range of species. To overcome these challenges, we developed GapSuite, an integrated auxiliary software toolbox that includes two complementary tools, Gap-Aid and Gap-Graph, which facilitate gap-filling through sequence-extension-based and assembly-graph-based strategies, respectively. The two tools empower users with limited computational expertise to efficiently perform gap closure on personal computers with just mouse clicks, resulting in a fully assembled genome. GapSuite incorporates several technical innovations to achieve key functions and improve both time and space efficiency. Their effectiveness was validated using Arabidopsis thaliana, rice and human genomes as well as simulated diploid and polyploid genomes. As case studies, we used the tools to construct, to the best of our knowledge, the first T2T genome of rice 9311, a model variety of indica rice, and to fill part of the remaining gaps in a recently published gapless poplar genome.
Additional Links: PMID-41643055
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@article {pmid41643055,
year = {2026},
author = {Xu, D and Zhao, X and Shang, L and Tian, S and Li, Y and Wen, H and Xu, Q and Li, D and Pan, W},
title = {Time-Efficient and Informatic-Skill-Light Gap-Filling for Telomere-to-Telomere Genome Assembly.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e18319},
doi = {10.1002/advs.202518319},
pmid = {41643055},
issn = {2198-3844},
support = {2025YFC3410300//National Key Research and Development Program of China/ ; 32470678//National Natural Science Foundation of China/ ; CAAS-ZDRW202503//Agricultural Science and Technology Innovation Program/ ; Y2025QC36//Youth Innovation Program of the Chinese Academy of Agricultural Sciences/ ; CAAS-CSIAF-202301//Innovation Program of Chinese Academy of Agricultural Sciences/ ; SKLTCBZRJJ202502//Project of State Key Laboratory of Tropical Crop Breeding/ ; //Science and Technology Project of the Ministry of Agriculture and Rural Affairs, P.R. China/ ; 202303021211069//Basic Research Programs of Shanxi Province/ ; },
abstract = {Despite remarkable advances in sequencing technologies and automated genome assembly algorithms, manual gap-filling remains indispensable for achieving telomere-to-telomere (T2T) genome assemblies, a process that can take weeks or even months. Additionally, these tasks require advanced bioinformatics expertise, thereby excluding many biologists from direct participation in T2T genome projects. This severely restricts the ability to construct T2T genomes for larger populations and a wider range of species. To overcome these challenges, we developed GapSuite, an integrated auxiliary software toolbox that includes two complementary tools, Gap-Aid and Gap-Graph, which facilitate gap-filling through sequence-extension-based and assembly-graph-based strategies, respectively. The two tools empower users with limited computational expertise to efficiently perform gap closure on personal computers with just mouse clicks, resulting in a fully assembled genome. GapSuite incorporates several technical innovations to achieve key functions and improve both time and space efficiency. Their effectiveness was validated using Arabidopsis thaliana, rice and human genomes as well as simulated diploid and polyploid genomes. As case studies, we used the tools to construct, to the best of our knowledge, the first T2T genome of rice 9311, a model variety of indica rice, and to fill part of the remaining gaps in a recently published gapless poplar genome.},
}
RevDate: 2026-02-05
RETRACTION: Arsenic Exposure Through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India.
Molecular carcinogenesis [Epub ahead of print].
D. Chatterjee, P. Bhattacharjee, T. J. Sau, J. K. Das, N. Sarma, A. K. Bandyopadhyay, S. S. Roy, and A. K. Giri, "Arsenic Exposure Through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India," Molecular Carcinogenesis 54, no. 9 (2015): 800-809, https://doi.org/10.1002/mc.22150. The above article, published online on 24 March 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by Wiley Periodicals LLC. The retraction has been agreed upon following concerns raised by a third-party regarding duplication between Figures 1a and 1b. Further investigation revealed multiple instances of similar background patterns in the western blots shown in Figures 1d and 4b. The authors provided an alternative image to correct Figure 1b; however evidence of duplication was also identified in this replacement. Given the nature of the concerns, the Publisher considers the results and conclusions to be unreliable. The authors disagree with the retraction.
Additional Links: PMID-41642722
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@article {pmid41642722,
year = {2026},
author = {},
title = {RETRACTION: Arsenic Exposure Through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India.},
journal = {Molecular carcinogenesis},
volume = {},
number = {},
pages = {},
doi = {10.1002/mc.70091},
pmid = {41642722},
issn = {1098-2744},
abstract = {D. Chatterjee, P. Bhattacharjee, T. J. Sau, J. K. Das, N. Sarma, A. K. Bandyopadhyay, S. S. Roy, and A. K. Giri, "Arsenic Exposure Through Drinking Water Leads to Senescence and Alteration of Telomere Length in Humans: A Case-Control Study in West Bengal, India," Molecular Carcinogenesis 54, no. 9 (2015): 800-809, https://doi.org/10.1002/mc.22150. The above article, published online on 24 March 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by Wiley Periodicals LLC. The retraction has been agreed upon following concerns raised by a third-party regarding duplication between Figures 1a and 1b. Further investigation revealed multiple instances of similar background patterns in the western blots shown in Figures 1d and 4b. The authors provided an alternative image to correct Figure 1b; however evidence of duplication was also identified in this replacement. Given the nature of the concerns, the Publisher considers the results and conclusions to be unreliable. The authors disagree with the retraction.},
}
RevDate: 2026-02-04
Efficient near-telomere-to-telomere assembly of nanopore simplex reads.
Nature [Epub ahead of print].
Telomere-to-telomere (T2T) assembly is the ultimate goal for de novo genome assembly. Existing algorithms[1,2] capable of near-T2T assembly all require Oxford Nanopore Technologies (ONT) ultra-long reads, which are costly and experimentally challenging to obtain and are thus often unavailable for samples without established cell lines[3]. Here we introduce hifiasm (ONT), an algorithm that can produce near-T2T assemblies from standard ONT simplex reads, eliminating the need for ultra-long sequencing. Compared with existing methods, hifiasm (ONT) reduces computational demands by an order of magnitude and reconstructs more chromosomes from telomere to telomere on the same datasets. This advance substantially broadens the feasibility of T2T assembly for applications previously limited by the high cost and experimental requirement of ultra-long reads.
Additional Links: PMID-41639459
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@article {pmid41639459,
year = {2026},
author = {Cheng, H and Qu, H and McKenzie, S and Lawrence, KR and Windsor, R and Vella, M and Park, PJ and Li, H},
title = {Efficient near-telomere-to-telomere assembly of nanopore simplex reads.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41639459},
issn = {1476-4687},
abstract = {Telomere-to-telomere (T2T) assembly is the ultimate goal for de novo genome assembly. Existing algorithms[1,2] capable of near-T2T assembly all require Oxford Nanopore Technologies (ONT) ultra-long reads, which are costly and experimentally challenging to obtain and are thus often unavailable for samples without established cell lines[3]. Here we introduce hifiasm (ONT), an algorithm that can produce near-T2T assemblies from standard ONT simplex reads, eliminating the need for ultra-long sequencing. Compared with existing methods, hifiasm (ONT) reduces computational demands by an order of magnitude and reconstructs more chromosomes from telomere to telomere on the same datasets. This advance substantially broadens the feasibility of T2T assembly for applications previously limited by the high cost and experimental requirement of ultra-long reads.},
}
RevDate: 2026-02-04
A telomere-to-telomere gap-free genome assembly of the protandrous maroon clownfish (Premnas biaculeatus).
Scientific data pii:10.1038/s41597-025-06538-9 [Epub ahead of print].
As a protandrous hermaphrodite with natural male-to-female sex change, maroon clownfish (Premnas biaculeatus) serves as an ideal model organism for investigating sequential hermaphroditism. However, genomic resources for this interesting species remain scarce, thereby limiting in-depth research on its unique biological traits. In this study, we generated the first telomere-to-telomere (T2T) gap-free genome assembly of maroon clownfish by integrating multi-platform sequencing data, including MGI short reads, PacBio HiFi long reads, ONT ultra-long reads, and Hi-C sequencing data. The final haplotypic genome spans 884.39 Mb, with all sequences successfully anchored onto 24 chromosomes. This assembly is highly contiguous, with a contig N50 of 37.98 Mb. Comprehensive genomic characterization revealed the precise localization of telomeric repeats and centromeric region within each chromosome. Independent quality assessments, such as QV of 71.01, CRAQ score of 98.98%, and BUSCO completeness of 99.98%, confirmed good assembly accuracy. Additionally, alignment of ONT ultra-long and PacBio HiFi reads to the assembly yielded a high mapping rate exceeding 99%, further validating a good assembly integrity. Repetitive elements constituted 33.51% (296.37 Mb) of the assembled genome, and a total of 24,556 protein-coding genes were annotated. This high-quality T2T genome assembly will not only provide a valuable genetic resource to advance related research in comparative genomics, population genetics, molecular breeding, and functional genomics of maroon clownfish, but also lay a solid foundation for resolving molecular mechanisms underlying its protandrous reproductive strategy.
Additional Links: PMID-41639094
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@article {pmid41639094,
year = {2026},
author = {Zhang, X and Hu, C and Chen, J and Yuan, M and Yang, Y and Li, T and Shi, Q},
title = {A telomere-to-telomere gap-free genome assembly of the protandrous maroon clownfish (Premnas biaculeatus).},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-025-06538-9},
pmid = {41639094},
issn = {2052-4463},
abstract = {As a protandrous hermaphrodite with natural male-to-female sex change, maroon clownfish (Premnas biaculeatus) serves as an ideal model organism for investigating sequential hermaphroditism. However, genomic resources for this interesting species remain scarce, thereby limiting in-depth research on its unique biological traits. In this study, we generated the first telomere-to-telomere (T2T) gap-free genome assembly of maroon clownfish by integrating multi-platform sequencing data, including MGI short reads, PacBio HiFi long reads, ONT ultra-long reads, and Hi-C sequencing data. The final haplotypic genome spans 884.39 Mb, with all sequences successfully anchored onto 24 chromosomes. This assembly is highly contiguous, with a contig N50 of 37.98 Mb. Comprehensive genomic characterization revealed the precise localization of telomeric repeats and centromeric region within each chromosome. Independent quality assessments, such as QV of 71.01, CRAQ score of 98.98%, and BUSCO completeness of 99.98%, confirmed good assembly accuracy. Additionally, alignment of ONT ultra-long and PacBio HiFi reads to the assembly yielded a high mapping rate exceeding 99%, further validating a good assembly integrity. Repetitive elements constituted 33.51% (296.37 Mb) of the assembled genome, and a total of 24,556 protein-coding genes were annotated. This high-quality T2T genome assembly will not only provide a valuable genetic resource to advance related research in comparative genomics, population genetics, molecular breeding, and functional genomics of maroon clownfish, but also lay a solid foundation for resolving molecular mechanisms underlying its protandrous reproductive strategy.},
}
RevDate: 2026-02-04
CmpDate: 2026-02-04
TARPON-A Telomere Analysis and Research Pipeline Optimized for Nanopore.
PLoS computational biology, 22(2):e1013915 pii:PCOMPBIOL-D-25-01744.
Long-read sequencing has transformed many areas of biology and holds significant promise for telomere research by enabling analysis of nucleotide-level resolution chromosome arm-specific telomere length in both model organisms and humans. However, the adoption of new technologies, particularly in clinical or diagnostic contexts, requires careful validation to recognize potential technical and computational limitations. We present TARPON (Telomere Analysis and Research Pipeline Optimized for Nanopore), a best-practices Nextflow pipeline designed for the analysis of telomeres sequenced on the Oxford Nanopore Technologies (ONT) platform. TARPON can be executed via the command line or integrated into ONT's EPI2ME agent, providing a user-friendly graphical interface for those without computational training. Nextflow's container-based architecture eliminates dependency conflicts, thereby streamlining deployment across platforms. TARPON isolates telomeric repeat-containing reads, assigns strand specificity, and identifies enrichment probes that can be used both for demultiplexing and for confirming capture-based library preparation. To ensure that the analysis is restricted to full-length telomeres, reads lacking a capture probe or non-telomeric sequence on the opposite end are excluded. A sliding-window approach defines the subtelomere-to-telomere boundary, followed by quality filtering to remove low-quality or subtelomeric reads that passed earlier steps. The pipeline generates customizable statistics, text-based summaries, and publication-ready visualizations (HTML, PNG, PDF). While default settings are optimized for diagnostic workflows, all parameters are easily adjustable via the GUI or command line to support diverse applications. These include telomere analyses in variant-rich samples (e.g., ALT-positive tumors) and organisms with non-canonical telomeric repeats such as some insects (GTTAG) and certain plants (GGTTTAG). TARPON is the first complete and experimentally validated pipeline for Nanopore-based telomere analysis requiring no data pre-processing or prior bioinformatics expertise, while offering flexibility for advanced users.
Additional Links: PMID-41637390
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@article {pmid41637390,
year = {2026},
author = {Deimler, N and Ho, DV and Paul, N and Gill, Z and Baumann, P},
title = {TARPON-A Telomere Analysis and Research Pipeline Optimized for Nanopore.},
journal = {PLoS computational biology},
volume = {22},
number = {2},
pages = {e1013915},
doi = {10.1371/journal.pcbi.1013915},
pmid = {41637390},
issn = {1553-7358},
mesh = {*Telomere/genetics ; Humans ; *Nanopores ; *High-Throughput Nucleotide Sequencing/methods ; Computational Biology/methods ; *Sequence Analysis, DNA/methods ; *Software ; *Nanopore Sequencing/methods ; Animals ; },
abstract = {Long-read sequencing has transformed many areas of biology and holds significant promise for telomere research by enabling analysis of nucleotide-level resolution chromosome arm-specific telomere length in both model organisms and humans. However, the adoption of new technologies, particularly in clinical or diagnostic contexts, requires careful validation to recognize potential technical and computational limitations. We present TARPON (Telomere Analysis and Research Pipeline Optimized for Nanopore), a best-practices Nextflow pipeline designed for the analysis of telomeres sequenced on the Oxford Nanopore Technologies (ONT) platform. TARPON can be executed via the command line or integrated into ONT's EPI2ME agent, providing a user-friendly graphical interface for those without computational training. Nextflow's container-based architecture eliminates dependency conflicts, thereby streamlining deployment across platforms. TARPON isolates telomeric repeat-containing reads, assigns strand specificity, and identifies enrichment probes that can be used both for demultiplexing and for confirming capture-based library preparation. To ensure that the analysis is restricted to full-length telomeres, reads lacking a capture probe or non-telomeric sequence on the opposite end are excluded. A sliding-window approach defines the subtelomere-to-telomere boundary, followed by quality filtering to remove low-quality or subtelomeric reads that passed earlier steps. The pipeline generates customizable statistics, text-based summaries, and publication-ready visualizations (HTML, PNG, PDF). While default settings are optimized for diagnostic workflows, all parameters are easily adjustable via the GUI or command line to support diverse applications. These include telomere analyses in variant-rich samples (e.g., ALT-positive tumors) and organisms with non-canonical telomeric repeats such as some insects (GTTAG) and certain plants (GGTTTAG). TARPON is the first complete and experimentally validated pipeline for Nanopore-based telomere analysis requiring no data pre-processing or prior bioinformatics expertise, while offering flexibility for advanced users.},
}
MeSH Terms:
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*Telomere/genetics
Humans
*Nanopores
*High-Throughput Nucleotide Sequencing/methods
Computational Biology/methods
*Sequence Analysis, DNA/methods
*Software
*Nanopore Sequencing/methods
Animals
RevDate: 2026-02-04
Flavonoid intake and telomere length attrition among middle-aged women: a cross-sectional analysis of the Nurses' Health Study.
GeroScience [Epub ahead of print].
Although mechanistic studies support a beneficial effect of several dietary flavonoids on telomere length (TL), to our knowledge no studies have examined associations between habitual flavonoid intakes and TL in population-based studies. We examined the associations between habitual intake of major flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and their polymers, and anthocyanins) and TL in a cross-sectional analysis of 4,944 disease-free females from the Nurses' Health Study (NHS). Flavonoid intakes were collected using food frequency questionnaire data, and TL was measured in peripheral blood leukocytes using quantitative real-time polymerase chain reaction. Multivariable-adjusted least squares mean leukocyte TL (z scores and corresponding standard error [SE]) for total and all flavonoid subclasses were calculated using generalized linear models. Although no individual flavonoid subclass was significantly associated with TL in the overall population, when we restricted analyses to younger and middle-aged participants (aged < 55 y), a higher anthocyanin intake associated with longer TL (least squares means ± SE: 0.06 ± 0.06 for the highest versus 0.24 ± 0.07 for the lowest quintile; P-trend = 0.042), corresponding to 6.6 (95% CI, 1.7-14.5) years of aging. In food-based analyses, participants aged < 55 y who consumed more berries had longer TL (Mean TL: 0.10 ± 0.04 for never/rarely; 0.21 ± 0.04 for ≤ 1 serving/week; 0.44 ± 0.26 for ≥ 2 servings/week; P = 0.033 for trend). Similarly, a higher anthocyanin intake was associated with longer TL among pre-menopausal females (0.46 ± 0.11 for the highest versus 0.02 ± 0.08 for the lowest quintile; P-trend = 0.001). Overall, habitual flavonoid intake was not associated with TL attrition in this cross-sectional analysis. However, in females aged < 55 y a higher anthocyanin intake was associated with longer TL, which raises the possibility that anthocyanin-rich foods may promote healthy aging and warrants further investigation with respect to age.
Additional Links: PMID-41637030
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@article {pmid41637030,
year = {2026},
author = {Li, S and De Vivo, I and Davinelli, S and Van Denburgh, M and Sorrenti, V and Scapagnini, G and Howard D Sesso, and Cassidy, A},
title = {Flavonoid intake and telomere length attrition among middle-aged women: a cross-sectional analysis of the Nurses' Health Study.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41637030},
issn = {2509-2723},
support = {UM1 CA186107/NH/NIH HHS/United States ; P01 CA87969/NH/NIH HHS/United States ; R01 CA49449/NH/NIH HHS/United States ; },
abstract = {Although mechanistic studies support a beneficial effect of several dietary flavonoids on telomere length (TL), to our knowledge no studies have examined associations between habitual flavonoid intakes and TL in population-based studies. We examined the associations between habitual intake of major flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and their polymers, and anthocyanins) and TL in a cross-sectional analysis of 4,944 disease-free females from the Nurses' Health Study (NHS). Flavonoid intakes were collected using food frequency questionnaire data, and TL was measured in peripheral blood leukocytes using quantitative real-time polymerase chain reaction. Multivariable-adjusted least squares mean leukocyte TL (z scores and corresponding standard error [SE]) for total and all flavonoid subclasses were calculated using generalized linear models. Although no individual flavonoid subclass was significantly associated with TL in the overall population, when we restricted analyses to younger and middle-aged participants (aged < 55 y), a higher anthocyanin intake associated with longer TL (least squares means ± SE: 0.06 ± 0.06 for the highest versus 0.24 ± 0.07 for the lowest quintile; P-trend = 0.042), corresponding to 6.6 (95% CI, 1.7-14.5) years of aging. In food-based analyses, participants aged < 55 y who consumed more berries had longer TL (Mean TL: 0.10 ± 0.04 for never/rarely; 0.21 ± 0.04 for ≤ 1 serving/week; 0.44 ± 0.26 for ≥ 2 servings/week; P = 0.033 for trend). Similarly, a higher anthocyanin intake was associated with longer TL among pre-menopausal females (0.46 ± 0.11 for the highest versus 0.02 ± 0.08 for the lowest quintile; P-trend = 0.001). Overall, habitual flavonoid intake was not associated with TL attrition in this cross-sectional analysis. However, in females aged < 55 y a higher anthocyanin intake was associated with longer TL, which raises the possibility that anthocyanin-rich foods may promote healthy aging and warrants further investigation with respect to age.},
}
RevDate: 2026-02-04
CmpDate: 2026-02-04
The fluoropyrimidine polymer CF10 synergizes with 5-ethynyl-2'-deoxyuridine by promoting telomere attrition and mitotic catastrophe.
NAR molecular medicine, 3(1):ugag005.
Fluoropyrimidine (FP) drugs, including 5-fluorouracil (5FU), are widely used to treat colorectal cancer (CRC) and target de novo thymidine biosynthesis, resulting in DNA damage and cell death. 5-ethynyl-2'-deoxyuridine (EdU) is a thymidine analog that also causes DNA damage. We investigated synergy between FPs and EdU potentially due to increased EdU incorporation into DNA under thymine-less conditions. Using the highest single agent model, strong synergy was observed between a 2nd-generation FP polymer, CF10, and EdU over a wide range of concentrations. In contrast, only additivity was observed for EdU + 5FU. CRC cells treated with synergistic EdU + CF10 combinations showed increased EdU incorporation into DNA, increased double-strand breaks (DSBs), and S-G2/M cell-cycle arrest. Phosphorylated histone H3 (pH3), a marker of highly condensed chromatin associated with mitosis, was detected in S- and G2/M-phase cells. Telomere staining was significantly reduced in CRC cells treated with EdU + CF10 combinations, and mitotic cells from these treatments showed mono- and multi-polar mitotic structures consistent with mitotic catastrophe. Our results are consistent with CF10 enhancing EdU incorporation into genomic DNA, causing DSBs but not extending telomeres, leading to telomere attrition and inducing mitotic catastrophe in CRC cells. This unique synergistic mechanism could lead to use of EdU + CF10 as a more effective CRC treatment.
Additional Links: PMID-41635782
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@article {pmid41635782,
year = {2026},
author = {Das, U and Behl, A and Gmeiner, WH},
title = {The fluoropyrimidine polymer CF10 synergizes with 5-ethynyl-2'-deoxyuridine by promoting telomere attrition and mitotic catastrophe.},
journal = {NAR molecular medicine},
volume = {3},
number = {1},
pages = {ugag005},
pmid = {41635782},
issn = {2976-856X},
abstract = {Fluoropyrimidine (FP) drugs, including 5-fluorouracil (5FU), are widely used to treat colorectal cancer (CRC) and target de novo thymidine biosynthesis, resulting in DNA damage and cell death. 5-ethynyl-2'-deoxyuridine (EdU) is a thymidine analog that also causes DNA damage. We investigated synergy between FPs and EdU potentially due to increased EdU incorporation into DNA under thymine-less conditions. Using the highest single agent model, strong synergy was observed between a 2nd-generation FP polymer, CF10, and EdU over a wide range of concentrations. In contrast, only additivity was observed for EdU + 5FU. CRC cells treated with synergistic EdU + CF10 combinations showed increased EdU incorporation into DNA, increased double-strand breaks (DSBs), and S-G2/M cell-cycle arrest. Phosphorylated histone H3 (pH3), a marker of highly condensed chromatin associated with mitosis, was detected in S- and G2/M-phase cells. Telomere staining was significantly reduced in CRC cells treated with EdU + CF10 combinations, and mitotic cells from these treatments showed mono- and multi-polar mitotic structures consistent with mitotic catastrophe. Our results are consistent with CF10 enhancing EdU incorporation into genomic DNA, causing DSBs but not extending telomeres, leading to telomere attrition and inducing mitotic catastrophe in CRC cells. This unique synergistic mechanism could lead to use of EdU + CF10 as a more effective CRC treatment.},
}
RevDate: 2026-02-04
Correction: Remnant cholesterol shows inverse and nonlinear associations with leukocyte telomere length and serum α-Klotho, mediated by inflammation and oxidative stress.
Frontiers in endocrinology, 16:1748130.
[This corrects the article DOI: 10.3389/fendo.2025.1700349.].
Additional Links: PMID-41635534
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@article {pmid41635534,
year = {2025},
author = {Xing, B and Yu, J and Liu, Y and Gao, Q and Chen, X and He, S and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {Correction: Remnant cholesterol shows inverse and nonlinear associations with leukocyte telomere length and serum α-Klotho, mediated by inflammation and oxidative stress.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1748130},
doi = {10.3389/fendo.2025.1748130},
pmid = {41635534},
issn = {1664-2392},
abstract = {[This corrects the article DOI: 10.3389/fendo.2025.1700349.].},
}
RevDate: 2026-02-04
Haplotype-resolved and near telomere-to-telomere assembly of the autotetraploid potato genome.
Genome biology pii:10.1186/s13059-026-03980-9 [Epub ahead of print].
BACKGROUND: Potato (Solanum tuberosum) breeding is severely hindered by its highly heterozygous autotetraploid genome, where complex allelic interactions impede precise trait selection. Reconstructing complete haplotype-resolved assemblies is crucial for genome-assisted breeding. However, current assembly methods for autopolyploids often generate fragmented sequences, haplotype-switch errors, and gaps in complex regions such as centromeres.
RESULTS: To address these challenges, we develop PHap, a haplotype assembly pipeline tailored for autopolyploids, using only standard sequencing data, including long-reads and Hi-C. Applying PHap to the autotetraploid potato cultivar HuaShu4, we generate a haplotype-resolved, near telomere-to-telomere assembly of 3.12 Gb with an N50 of 32.7 Mb and 99.7% haplotype accuracy. Comparisons with alternative methods and existing assemblies highlight PHap's advantages in assembly quality and cost-effectiveness. Integration of transcriptomic and epigenomic data demonstrates that the genomic and methylation divergence across haplotypes drives substantial allelic expression differentiation. Time-course RNA-seq further reveals, for the first time, that 55% of genes exhibit divergent allelic expression, with dynamic shifts in dominant or suppressed alleles during tuber development. Additionally, our assembly resolves high-resolution haplotype-specific structures in centromeres and subtelomeres, as well as haplotype divergence of structural rearrangements. It also shows neocentromere formation via the expansion of megabase-scale satellite arrays.
CONCLUSIONS: These findings provide insights into the architecture of autopolyploid genomes and establish a foundation for genomics-assisted breeding of polyploid potatoes.
Additional Links: PMID-41634861
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@article {pmid41634861,
year = {2026},
author = {Xiao, PX and Tan, L and Dong, J and Huang, J and Huang, Y and He, JB and Su, H and Song, B and Jiao, WB},
title = {Haplotype-resolved and near telomere-to-telomere assembly of the autotetraploid potato genome.},
journal = {Genome biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13059-026-03980-9},
pmid = {41634861},
issn = {1474-760X},
support = {32270685//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Potato (Solanum tuberosum) breeding is severely hindered by its highly heterozygous autotetraploid genome, where complex allelic interactions impede precise trait selection. Reconstructing complete haplotype-resolved assemblies is crucial for genome-assisted breeding. However, current assembly methods for autopolyploids often generate fragmented sequences, haplotype-switch errors, and gaps in complex regions such as centromeres.
RESULTS: To address these challenges, we develop PHap, a haplotype assembly pipeline tailored for autopolyploids, using only standard sequencing data, including long-reads and Hi-C. Applying PHap to the autotetraploid potato cultivar HuaShu4, we generate a haplotype-resolved, near telomere-to-telomere assembly of 3.12 Gb with an N50 of 32.7 Mb and 99.7% haplotype accuracy. Comparisons with alternative methods and existing assemblies highlight PHap's advantages in assembly quality and cost-effectiveness. Integration of transcriptomic and epigenomic data demonstrates that the genomic and methylation divergence across haplotypes drives substantial allelic expression differentiation. Time-course RNA-seq further reveals, for the first time, that 55% of genes exhibit divergent allelic expression, with dynamic shifts in dominant or suppressed alleles during tuber development. Additionally, our assembly resolves high-resolution haplotype-specific structures in centromeres and subtelomeres, as well as haplotype divergence of structural rearrangements. It also shows neocentromere formation via the expansion of megabase-scale satellite arrays.
CONCLUSIONS: These findings provide insights into the architecture of autopolyploid genomes and establish a foundation for genomics-assisted breeding of polyploid potatoes.},
}
RevDate: 2026-02-03
Leukocyte telomere length and circulating MiRNAs in relation to cardiovascular outcomes in older adults.
BMC geriatrics pii:10.1186/s12877-026-07042-4 [Epub ahead of print].
Additional Links: PMID-41629836
Publisher:
PubMed:
Citation:
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@article {pmid41629836,
year = {2026},
author = {La Grotta, R and Crocco, P and Leonova, A and Cosimo, SC and Morelli, F and Dato, S and Passarino, G and Rose, G},
title = {Leukocyte telomere length and circulating MiRNAs in relation to cardiovascular outcomes in older adults.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07042-4},
pmid = {41629836},
issn = {1471-2318},
support = {cod. 20227KNBEJ//Ministero dell'Università e della Ricerca/ ; DM 1557 11.10.2022//Ministero della Salute/ ; },
}
RevDate: 2026-02-02
CmpDate: 2026-02-02
Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.
Frontiers in immunology, 16:1718107.
Telomeres are repetitive nucleotide sequences at the ends of chromosomes that preserve genomic integrity. Defects in telomere maintenance mechanisms lead to premature telomere shortening, resulting in cellular senescence, apoptosis, and organ dysfunction, collectively termed telomere biology disorders (TBDs). Short telomere length is associated with an increased risk of end-stage fibrotic disease of the lung and/or liver, which may necessitate lung or liver transplantation. Beyond pulmonary and hepatic involvement, TBDs can also affect cardiac and renal function. Importantly, the bone marrow function is often also compromised, which can significantly influence transplant outcomes. Although evidence remains scarce, particularly in non-lung solid organ transplant recipients, post-transplant immunosuppressive therapy, typically including corticosteroids, calcineurin inhibitors, and cell cycle inhibitors, may exacerbate the underlying hematopoietic fragility in TBD patients. Hematological complications may result from both the intrinsic TBD and the additive myelotoxic effects of immunosuppressive agents (e.g., azathioprine, mycophenolate mofetil) or anti-infectious prophylaxis (e.g., trimethoprim-sulfamethoxazole, valganciclovir). Early recognition of TBDs prior to transplantation is essential. Assessment of telomere length and genetic testing should be considered in at-risk candidates, particularly those with early-onset pulmonary fibrosis, unexplained cytopenia, cryptogenic liver disease, or a family history suggestive of TBD. A multidisciplinary approach involving pulmonology, hepatology, hematology, and transplant specialists is crucial to optimize patient selection, perioperative management, and post-transplant care. This review summarizes current knowledge on hematological complications following solid organ transplantation in TBD patients and describes expert-opinion strategies for the pre-transplant evaluation and post-transplant management of these high-risk individuals.
Additional Links: PMID-41624889
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@article {pmid41624889,
year = {2025},
author = {Carlier, FM and Planté-Bordeneuve, T and Froidure, A and Graux, C and van Dievoet, MA and van Moorsel, CHM and Hoffman, TW},
title = {Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1718107},
pmid = {41624889},
issn = {1664-3224},
mesh = {Humans ; *Organ Transplantation/adverse effects ; *Telomere/genetics ; Transplant Recipients ; *Hematologic Diseases/etiology/diagnosis ; Immunosuppressive Agents/adverse effects ; Telomere Shortening ; },
abstract = {Telomeres are repetitive nucleotide sequences at the ends of chromosomes that preserve genomic integrity. Defects in telomere maintenance mechanisms lead to premature telomere shortening, resulting in cellular senescence, apoptosis, and organ dysfunction, collectively termed telomere biology disorders (TBDs). Short telomere length is associated with an increased risk of end-stage fibrotic disease of the lung and/or liver, which may necessitate lung or liver transplantation. Beyond pulmonary and hepatic involvement, TBDs can also affect cardiac and renal function. Importantly, the bone marrow function is often also compromised, which can significantly influence transplant outcomes. Although evidence remains scarce, particularly in non-lung solid organ transplant recipients, post-transplant immunosuppressive therapy, typically including corticosteroids, calcineurin inhibitors, and cell cycle inhibitors, may exacerbate the underlying hematopoietic fragility in TBD patients. Hematological complications may result from both the intrinsic TBD and the additive myelotoxic effects of immunosuppressive agents (e.g., azathioprine, mycophenolate mofetil) or anti-infectious prophylaxis (e.g., trimethoprim-sulfamethoxazole, valganciclovir). Early recognition of TBDs prior to transplantation is essential. Assessment of telomere length and genetic testing should be considered in at-risk candidates, particularly those with early-onset pulmonary fibrosis, unexplained cytopenia, cryptogenic liver disease, or a family history suggestive of TBD. A multidisciplinary approach involving pulmonology, hepatology, hematology, and transplant specialists is crucial to optimize patient selection, perioperative management, and post-transplant care. This review summarizes current knowledge on hematological complications following solid organ transplantation in TBD patients and describes expert-opinion strategies for the pre-transplant evaluation and post-transplant management of these high-risk individuals.},
}
MeSH Terms:
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Humans
*Organ Transplantation/adverse effects
*Telomere/genetics
Transplant Recipients
*Hematologic Diseases/etiology/diagnosis
Immunosuppressive Agents/adverse effects
Telomere Shortening
RevDate: 2026-02-02
CmpDate: 2026-02-02
Optimized primer and model improve precision of X chromosome telomere length determination in the Han population.
iScience, 29(2):114600.
The attrition of telomere length is associated with cellular aging and plays a role in multiple age-related disorders. This study analyzed the relationship between telomere length on the X chromosome and age in the Han population (n = 492) using whole-genome sequencing and long-read sequencing data from 32 individuals. We developed three pairs of primers and completed measurements in a cohort of 124 individuals. We then constructed an online prediction tool based on a three-layer feedforward neural network and validated its performance in an independent cohort of 41 individuals. Our results revealed a complex association between X chromosome telomere length and aging. No significant changes were observed in individuals under 30, while a significant negative correlation emerged in the population over 40, suggesting a potential "telomere shortening accelerating point (TSAP)" around this age. This finding challenges the conventional view of linear telomere shortening, and our model provides effective tools for exploring aging mechanisms.
Additional Links: PMID-41623485
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@article {pmid41623485,
year = {2026},
author = {Zhang, Z and Sun, X and Shi, J and Xu, H and Wang, H and Yang, Z and Guo, J and Yang, Z and Li, C and Zhu, J and Zhang, Y and Zheng, P and Xue, X and Mi, Y},
title = {Optimized primer and model improve precision of X chromosome telomere length determination in the Han population.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114600},
pmid = {41623485},
issn = {2589-0042},
abstract = {The attrition of telomere length is associated with cellular aging and plays a role in multiple age-related disorders. This study analyzed the relationship between telomere length on the X chromosome and age in the Han population (n = 492) using whole-genome sequencing and long-read sequencing data from 32 individuals. We developed three pairs of primers and completed measurements in a cohort of 124 individuals. We then constructed an online prediction tool based on a three-layer feedforward neural network and validated its performance in an independent cohort of 41 individuals. Our results revealed a complex association between X chromosome telomere length and aging. No significant changes were observed in individuals under 30, while a significant negative correlation emerged in the population over 40, suggesting a potential "telomere shortening accelerating point (TSAP)" around this age. This finding challenges the conventional view of linear telomere shortening, and our model provides effective tools for exploring aging mechanisms.},
}
RevDate: 2026-02-01
CmpDate: 2026-02-01
The telomere-to-telomere haplotype genome provides in-depth insights into the molecular mechanisms of the anthocyanin deficiency phenotype in Prunus mume.
Molecular horticulture, 6(1):8.
Prunus mume originated from China and is highly valued for its remarkable combination of ornamental blossoms and high economic value. Previously published P. mume genomes contain unanchored genetic regions and excessive gaps. Here, we report the P. mume f. viridicalyx gap-free telomere-to-telomere (T2T) haplotype genome. The LE_hap1 and LE_hap2 genomes were 229.29 and 228.36 Mb in length, respectively, with an N50 length of the contig between 27.65 and 27.79 Mb and 24,318 and 24,316 protein-coding genes, respectively. The completeness, continuity, and accuracy of the P. mume f. viridicalyx genome was significantly improved over the previous P. mume genomes. The key mutated genes during P. mume f. viridicalyx cultivar domestication were identified by comparative genomic, population evolution, and selective sweep analyses to be significantly enriched in the anthocyanin metabolism process, glutathione metabolism process, and carotenoid biosynthesis. Further analysis revealed that early codon termination of the PmGSTF2 gene, which is the key gene for the characteristic production of P. mume f. viridicalyx, reduced anthocyanin accumulation. We assembled a complete T2T gap-free haplotype P. mume genome, which provides a reference for gene mining and genome evolution of the anthocyanin deficiency phenotype in P. mume.
Additional Links: PMID-41622248
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Citation:
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@article {pmid41622248,
year = {2026},
author = {Zhou, P and Huang, X and Tan, W and Gao, F and Bai, Y and Ma, C and Lin, X and Ma, Y and Li, M and Ni, Z and Shi, T and Hayat, F and Shao, J and Gao, Z},
title = {The telomere-to-telomere haplotype genome provides in-depth insights into the molecular mechanisms of the anthocyanin deficiency phenotype in Prunus mume.},
journal = {Molecular horticulture},
volume = {6},
number = {1},
pages = {8},
pmid = {41622248},
issn = {2730-9401},
support = {JBGS [2021] 019//the "JBGS" Project of Seed Industry Revitalization in Jiangsu Province/ ; KYZZ2025006, KJYQ2024029//Fundamental Research Funds for the Central Universities/ ; 2023M731734//China Postdoctoral Science Foundation/ ; 2023ZB729//Jiangsu Excellence Postdoctoral Program/ ; PAPD//the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; },
abstract = {Prunus mume originated from China and is highly valued for its remarkable combination of ornamental blossoms and high economic value. Previously published P. mume genomes contain unanchored genetic regions and excessive gaps. Here, we report the P. mume f. viridicalyx gap-free telomere-to-telomere (T2T) haplotype genome. The LE_hap1 and LE_hap2 genomes were 229.29 and 228.36 Mb in length, respectively, with an N50 length of the contig between 27.65 and 27.79 Mb and 24,318 and 24,316 protein-coding genes, respectively. The completeness, continuity, and accuracy of the P. mume f. viridicalyx genome was significantly improved over the previous P. mume genomes. The key mutated genes during P. mume f. viridicalyx cultivar domestication were identified by comparative genomic, population evolution, and selective sweep analyses to be significantly enriched in the anthocyanin metabolism process, glutathione metabolism process, and carotenoid biosynthesis. Further analysis revealed that early codon termination of the PmGSTF2 gene, which is the key gene for the characteristic production of P. mume f. viridicalyx, reduced anthocyanin accumulation. We assembled a complete T2T gap-free haplotype P. mume genome, which provides a reference for gene mining and genome evolution of the anthocyanin deficiency phenotype in P. mume.},
}
RevDate: 2026-02-01
Telomere-based Risk Model for Prognosis Prediction in Clear Cell Renal Cell Carcinoma.
Current medicinal chemistry pii:CMC-EPUB-152401 [Epub ahead of print].
INTRODUCTION: Telomeres have become extensively studied in renal cell carcinoma (RCC), and this study aims to identify relevant diagnostic biomarkers in the predominant RCC subtype, clear cell RCC (ccRCC).
MATERIALS AND METHODS: This study retrieved telomere-related genes from the TelNet database and integrated data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to calculate telomere enrichment scores using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were then applied to identify candidate genes, which were further refined through protein-protein interaction (PPI) network construction and two machine learning methods: least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE). The associations between the identified feature genes and immune cell infiltration were subsequently evaluated using CIBERSORT and ESTIMATE. Furthermore, single-cell analysis was employed to determine the highly expressed genes in different cell clusters. Finally, using a ccRCC cell line, quantitative real-time PCR, wound healing, and Transwell assays were performed to validate the expression and potential biological functions of the selected key genes.
RESULTS: A higher telomere score was observed in ccRCC. The common genes from the DEGs and the gene modules were mainly enriched in cell division- and senescence-related pathways. Moreover, six genes (ASPM, CENPF, CEP55, MELK, BUB1, and EXO1) were identified as feature genes with satisfactory diagnostic efficacy and high expression in ccRCC; they were positively correlated with most immune cells and highly expressed in T cells. Notably, CEP55 knockdown suppressed the migration and invasion of ccRCC cells.
DISCUSSION: Our present study, based on the data from the public databases, unraveled 6 genes with diagnostic efficacy in ccRCC, which may aid the development of a relevant future diagnostic method in ccRCC.
CONCLUSION: This study identified six telomere-related genes with high expression and strong diagnostic value in ccRCC, highlighting their association with immune infiltration and potential as diagnostic and therapeutic targets.
Additional Links: PMID-41620921
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PubMed:
Citation:
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@article {pmid41620921,
year = {2026},
author = {Guo, S and Chen, C and Guo, Y and Zhou, D and Ruan, J},
title = {Telomere-based Risk Model for Prognosis Prediction in Clear Cell Renal Cell Carcinoma.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673424522251103073120},
pmid = {41620921},
issn = {1875-533X},
abstract = {INTRODUCTION: Telomeres have become extensively studied in renal cell carcinoma (RCC), and this study aims to identify relevant diagnostic biomarkers in the predominant RCC subtype, clear cell RCC (ccRCC).
MATERIALS AND METHODS: This study retrieved telomere-related genes from the TelNet database and integrated data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to calculate telomere enrichment scores using single-sample gene set enrichment analysis (ssGSEA). Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were then applied to identify candidate genes, which were further refined through protein-protein interaction (PPI) network construction and two machine learning methods: least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE). The associations between the identified feature genes and immune cell infiltration were subsequently evaluated using CIBERSORT and ESTIMATE. Furthermore, single-cell analysis was employed to determine the highly expressed genes in different cell clusters. Finally, using a ccRCC cell line, quantitative real-time PCR, wound healing, and Transwell assays were performed to validate the expression and potential biological functions of the selected key genes.
RESULTS: A higher telomere score was observed in ccRCC. The common genes from the DEGs and the gene modules were mainly enriched in cell division- and senescence-related pathways. Moreover, six genes (ASPM, CENPF, CEP55, MELK, BUB1, and EXO1) were identified as feature genes with satisfactory diagnostic efficacy and high expression in ccRCC; they were positively correlated with most immune cells and highly expressed in T cells. Notably, CEP55 knockdown suppressed the migration and invasion of ccRCC cells.
DISCUSSION: Our present study, based on the data from the public databases, unraveled 6 genes with diagnostic efficacy in ccRCC, which may aid the development of a relevant future diagnostic method in ccRCC.
CONCLUSION: This study identified six telomere-related genes with high expression and strong diagnostic value in ccRCC, highlighting their association with immune infiltration and potential as diagnostic and therapeutic targets.},
}
RevDate: 2026-01-31
Quantile regression of the relationship between demographic factors and leukocyte telomere length, measured by Southern blot and qPCR.
GeroScience [Epub ahead of print].
Telomere length (TL) is associated with health outcomes. Southern Blotting (SB) is the gold standard of TL measurements, while qPCR-based TL measurements are the most used because of their high throughput. We compared leukocyte TL (LTL) measurements by SB and qPCR, and their ability to capture LTL associations with demographic factors. This study included 908 healthy donors for hematopoietic cell transplantation who had blood samples and data available at CIBMTR®. We used quantile regression (QR) to assess the associations between selected demographic factors and LTL across the LTL distribution. Pearson correlation coefficient and Bland-Altman plot were used to compare SB-LTL and qPCR-LTL measurements. SB-LTL and qPCR-LTL were modestly correlated (r = 0.58, P < 0.001). On average, SB-LTL shortened by 29 base pairs (bp) per year and was 190 bp longer in females than in males. QR analyses showed that the association between SB-LTL and age varied across the LTL distribution, with stronger age-related shortening at higher percentiles (25 bp at the 25th percentile vs. 31 bp at the 75th percentile; P = 0.003). Females had longer SB-LTL than males across all percentiles (P < 0.05 in SB-LTL analysis), and the magnitude of this sex difference did not vary significantly across the LTL distribution (157 bp at the 25th percentile vs. 221 bp at the 75th percentile; P = 0.33). Both SB and qPCR showed an inverse relationship between LTL and age, though the magnitudes differed between methods. Considering the full LTL distribution in studies of lifestyle factors and diseases may provide better molecular insights and guide LTL utilization in health applications.
Additional Links: PMID-41619133
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Citation:
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@article {pmid41619133,
year = {2026},
author = {Mendez, KJW and Lee, SK and Dagnall, C and Lai, TP and Katki, H and Spellman, SR and Stewart, V and Aviv, A and Gadalla, SM and Hong, HG},
title = {Quantile regression of the relationship between demographic factors and leukocyte telomere length, measured by Southern blot and qPCR.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41619133},
issn = {2509-2723},
support = {U01AG066529/NH/NIH HHS/United States ; U24CA076518/NH/NIH HHS/United States ; 75R60222C00011//HRSA/ ; N00014-24-1-2057//Office of Naval Research/ ; N00014-25-1-2146//Office of Naval Research/ ; 75N910D00024/CA/NCI NIH HHS/United States ; },
abstract = {Telomere length (TL) is associated with health outcomes. Southern Blotting (SB) is the gold standard of TL measurements, while qPCR-based TL measurements are the most used because of their high throughput. We compared leukocyte TL (LTL) measurements by SB and qPCR, and their ability to capture LTL associations with demographic factors. This study included 908 healthy donors for hematopoietic cell transplantation who had blood samples and data available at CIBMTR®. We used quantile regression (QR) to assess the associations between selected demographic factors and LTL across the LTL distribution. Pearson correlation coefficient and Bland-Altman plot were used to compare SB-LTL and qPCR-LTL measurements. SB-LTL and qPCR-LTL were modestly correlated (r = 0.58, P < 0.001). On average, SB-LTL shortened by 29 base pairs (bp) per year and was 190 bp longer in females than in males. QR analyses showed that the association between SB-LTL and age varied across the LTL distribution, with stronger age-related shortening at higher percentiles (25 bp at the 25th percentile vs. 31 bp at the 75th percentile; P = 0.003). Females had longer SB-LTL than males across all percentiles (P < 0.05 in SB-LTL analysis), and the magnitude of this sex difference did not vary significantly across the LTL distribution (157 bp at the 25th percentile vs. 221 bp at the 75th percentile; P = 0.33). Both SB and qPCR showed an inverse relationship between LTL and age, though the magnitudes differed between methods. Considering the full LTL distribution in studies of lifestyle factors and diseases may provide better molecular insights and guide LTL utilization in health applications.},
}
RevDate: 2026-01-31
Epigenome-wide association study of leukocyte telomere length and their effects on smoking-induced lung tumorigenesis: insights from the Dongfeng-Tongji cohort study.
Clinical epigenetics pii:10.1186/s13148-026-02053-9 [Epub ahead of print].
BACKGROUND: Epigenetic factors underlying telomere length (TL) may provide insight into telomeric homeostasis, with direct links to cigarette smoking and lung cancer susceptibility. It is unclear, nevertheless, to what extent effects of TL and its related DNA methylation on the smoking-induced lung tumorigenesis.
METHODS: A case-cohort study is performed within the Dongfeng-Tongji (DFTJ) cohort, including a randomly selected subcohort of 1399 subjects and 359 incident lung cancer cases. We use a linear regression model to conduct EWAS of TL, while the associations of TL and candidate CpGs with lung cancer risk are evaluated using weighted Cox proportional hazard regression models. Furthermore, the causal inference test (CIT) and mediation analysis are used to elucidate the causality of TL and its relevant CpGs in the smoking-induced lung tumorigenesis. The methylation-expression associations are assessed in SY panel (n = 144), adjacent normal lung tissues (n = 32) and solid normal tissues in TCGA (n = 375).
RESULTS: We identified 31 CpGs with significant associations with TL at FDR < 0.05, and their annotated genes are mainly enriched in oxidative stress, energy metabolism and immunity regulation pathways. Among the 31 TL-related CpGs, 3 CpGs showed substantial associations with both lung cancer risk and smoking status (all FDR < 0.1), including cg26563141 in RGPD1/RGPD2, cg03964851in MIR1974/KIAA0825, and cg08976633 in ZNF74. The further mediation analyses suggest that these three CpGs could mediate 2.89%~8.83% effect on lung cancer risk induced by smoking (all FDR < 0.1). The further CIT and multiple mediation analysis reveal that the effect of smoking on lung cancer risk is primarily mediated by TL (> 10%) while being mildly mediated via DNA methylation pathway (< 1%). Also, hypermethylation of cg26563141 is related to low expression of RGPD1 and RGPD2 across blood and tissue samples.
CONCLUSIONS: Both TL attrition and the three candidate CpGs showed significant mediation effects on lung cancer risk induced by smoking. These findings provide novel insight into the epigenetic control of telomere homeostasis mechanisms and clues for methylation alteration and TL in smoking-induced lung tumorigenesis.
Additional Links: PMID-41618404
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PubMed:
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@article {pmid41618404,
year = {2026},
author = {Guan, X and Zhou, Y and Hong, S and Jiang, Y and Xiao, Y and Wang, C and Fu, M and Zhao, H and Chen, S and Fu, Y and Zhang, Y and Bai, Y and Wang, Y and You, Y and Zhang, Y and Cheng, S and Guo, H},
title = {Epigenome-wide association study of leukocyte telomere length and their effects on smoking-induced lung tumorigenesis: insights from the Dongfeng-Tongji cohort study.},
journal = {Clinical epigenetics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13148-026-02053-9},
pmid = {41618404},
issn = {1868-7083},
support = {2024ZD0543200//the Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 82504505//National Natural Science Foundation of China/ ; 82373667, 82073650 and 82021005//National Natural Science Foundation of China/ ; GZC20250500//Postdoctoral Fellowship Program and China Postdoctoral Science Foundation/ ; 2022CFA098//Natural Science Foundation of Hubei Province/ ; },
abstract = {BACKGROUND: Epigenetic factors underlying telomere length (TL) may provide insight into telomeric homeostasis, with direct links to cigarette smoking and lung cancer susceptibility. It is unclear, nevertheless, to what extent effects of TL and its related DNA methylation on the smoking-induced lung tumorigenesis.
METHODS: A case-cohort study is performed within the Dongfeng-Tongji (DFTJ) cohort, including a randomly selected subcohort of 1399 subjects and 359 incident lung cancer cases. We use a linear regression model to conduct EWAS of TL, while the associations of TL and candidate CpGs with lung cancer risk are evaluated using weighted Cox proportional hazard regression models. Furthermore, the causal inference test (CIT) and mediation analysis are used to elucidate the causality of TL and its relevant CpGs in the smoking-induced lung tumorigenesis. The methylation-expression associations are assessed in SY panel (n = 144), adjacent normal lung tissues (n = 32) and solid normal tissues in TCGA (n = 375).
RESULTS: We identified 31 CpGs with significant associations with TL at FDR < 0.05, and their annotated genes are mainly enriched in oxidative stress, energy metabolism and immunity regulation pathways. Among the 31 TL-related CpGs, 3 CpGs showed substantial associations with both lung cancer risk and smoking status (all FDR < 0.1), including cg26563141 in RGPD1/RGPD2, cg03964851in MIR1974/KIAA0825, and cg08976633 in ZNF74. The further mediation analyses suggest that these three CpGs could mediate 2.89%~8.83% effect on lung cancer risk induced by smoking (all FDR < 0.1). The further CIT and multiple mediation analysis reveal that the effect of smoking on lung cancer risk is primarily mediated by TL (> 10%) while being mildly mediated via DNA methylation pathway (< 1%). Also, hypermethylation of cg26563141 is related to low expression of RGPD1 and RGPD2 across blood and tissue samples.
CONCLUSIONS: Both TL attrition and the three candidate CpGs showed significant mediation effects on lung cancer risk induced by smoking. These findings provide novel insight into the epigenetic control of telomere homeostasis mechanisms and clues for methylation alteration and TL in smoking-induced lung tumorigenesis.},
}
RevDate: 2026-02-01
CmpDate: 2026-02-01
Intima-media thickness, telomere length and neuropsychological status: is there any connection?.
Wiadomosci lekarskie (Warsaw, Poland : 1960), 78(12):2661-2668.
OBJECTIVE: Aim: To determine the relationship between telomere length and telomerase activity and indicators of oxidative stress in patients with СА and T2DM.
PATIENTS AND METHODS: Materials and Methods: to investigate relationship between telomere length and cognitive function and identify predictors of cognitive impairment in patients with cerebral atherosclerosis and type 2 diabetes mellitus. The MMSE and MoCA scales, which are widely used in most modern epidemiological and clinical studies, were used for screening and assessment of cognitive disorders.
RESULTS: Results: Patients were divided into 2 groups: I - with scores on MMSE scale < 26 (moderate cognitive deficit, 26 people), II - with scores on MMSE scale 3 26 (mild cognitive deficit, 135 people). As a result of analysis, it was found that length of telomeres was statistically significantly shorter in patients of group I, the patients studied less, they had more pronounced situational anxiety, more pronounced intima-media thickness in both carotid arteries, and according to MoCA scale, they had pronounced impairment of cognitive functions (p<0.05). Group II patients had longer telomeres, studied longer, and had high personal anxiety.
CONCLUSION: Conclusions: patients with cerebral atherosclerosis and type 2 diabetes mellitus with mild cognitive impairment have longer telomeres, high personal anxiety, and a higher level of education.
Additional Links: PMID-41620865
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@article {pmid41620865,
year = {2025},
author = {Cherska, M and Kukharchuk, K},
title = {Intima-media thickness, telomere length and neuropsychological status: is there any connection?.},
journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)},
volume = {78},
number = {12},
pages = {2661-2668},
doi = {10.36740/WLek/213488},
pmid = {41620865},
issn = {0043-5147},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Carotid Intima-Media Thickness ; *Diabetes Mellitus, Type 2/complications ; *Cognitive Dysfunction ; *Telomere ; Aged ; *Intracranial Arteriosclerosis/complications ; Neuropsychological Tests ; Oxidative Stress ; },
abstract = {OBJECTIVE: Aim: To determine the relationship between telomere length and telomerase activity and indicators of oxidative stress in patients with СА and T2DM.
PATIENTS AND METHODS: Materials and Methods: to investigate relationship between telomere length and cognitive function and identify predictors of cognitive impairment in patients with cerebral atherosclerosis and type 2 diabetes mellitus. The MMSE and MoCA scales, which are widely used in most modern epidemiological and clinical studies, were used for screening and assessment of cognitive disorders.
RESULTS: Results: Patients were divided into 2 groups: I - with scores on MMSE scale < 26 (moderate cognitive deficit, 26 people), II - with scores on MMSE scale 3 26 (mild cognitive deficit, 135 people). As a result of analysis, it was found that length of telomeres was statistically significantly shorter in patients of group I, the patients studied less, they had more pronounced situational anxiety, more pronounced intima-media thickness in both carotid arteries, and according to MoCA scale, they had pronounced impairment of cognitive functions (p<0.05). Group II patients had longer telomeres, studied longer, and had high personal anxiety.
CONCLUSION: Conclusions: patients with cerebral atherosclerosis and type 2 diabetes mellitus with mild cognitive impairment have longer telomeres, high personal anxiety, and a higher level of education.},
}
MeSH Terms:
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Humans
Male
Female
Middle Aged
*Carotid Intima-Media Thickness
*Diabetes Mellitus, Type 2/complications
*Cognitive Dysfunction
*Telomere
Aged
*Intracranial Arteriosclerosis/complications
Neuropsychological Tests
Oxidative Stress
RevDate: 2026-01-30
Telomere length, common variants, and rare variants in IPF: a trio of key risk determinants.
The Lancet. Respiratory medicine pii:S2213-2600(25)00456-4 [Epub ahead of print].
Additional Links: PMID-41616792
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PubMed:
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@article {pmid41616792,
year = {2026},
author = {Manali, ED and Borie, R and Kannengiesser, C and Papiris, SA},
title = {Telomere length, common variants, and rare variants in IPF: a trio of key risk determinants.},
journal = {The Lancet. Respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2213-2600(25)00456-4},
pmid = {41616792},
issn = {2213-2619},
}
RevDate: 2026-01-30
Independent and interaction effects of telomere length and life's essential 8 score on the risk of type 2 diabetes mellitus: Findings from a large prospective cohort study.
Maturitas, 206:108828 pii:S0378-5122(26)00005-8 [Epub ahead of print].
OBJECTIVE: To investigate the independent and joint effects of leukocyte telomere length and score on the Life's Essential 8 scale on type 2 diabetes mellitus risk using UK Biobank data.
METHODS: A total of 309,288 participants without type 2 diabetes mellitus at baseline were included. Leukocyte telomere length was categorized into quartiles (Q1-Q4), and Life's Essential 8 scores into three groups: low (< 50 points), intermediate (50-79 points) and high (≥ 80 points). Cox proportional-hazards models were used to estimate hazard ratios (HRs) for T2DM. Multiplicative and additive models assessed interactions between leukocyte telomere length and Life's Essential 8 score.
RESULTS: Over a median follow-up of 13.33 years, 9830 participants developed T2DM. Compared with group Q1, the risk of T2DM was reduced by 7% (HR = 0.93, 95%CI: 0.88, 0.99) in the Q4 group. Compared with the low Life's Essential 8 score group, the risk of T2DM was reduced by 70% (HR = 0.30, 95%CI: 0.29, 0.31) and 93% (HR = 0.07, 95%CI: 0.06, 0.08) in the intermediate and high score groups, respectively. The group with long leukocyte telomere length and high Life's Essential 8 score had the most significant reduction in T2DM risk compared with the group with short leukocyte telomere length and low Life's Essential 8 score (HR = 0.07, 95%CI: 0.05, 0.08). Both multiplicative (Pinteraction < 0.001) and additive interactions (S = 1.12, 95%CI: 1.01, 1.25) were observed between the effects of leukocyte telomere length and Life's Essential 8 score on T2DM.
CONCLUSION: Elevated leukocyte telomere length and Life's Essential 8 scores synergistically reduce T2DM risk beyond their individual effects, underscoring the importance of integrated strategies that simultaneously target leukocyte telomere length maintenance and the optimization of cardiovascular-metabolic health in the prevention of T2DM.
Additional Links: PMID-41616669
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PubMed:
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@article {pmid41616669,
year = {2026},
author = {Chen, T and Su, Y and Yang, L and Gu, M and Liang, J and Li, K and Shu, Y and Chen, K and Pang, J and Hu, D and Hu, F and Zhang, M},
title = {Independent and interaction effects of telomere length and life's essential 8 score on the risk of type 2 diabetes mellitus: Findings from a large prospective cohort study.},
journal = {Maturitas},
volume = {206},
number = {},
pages = {108828},
doi = {10.1016/j.maturitas.2026.108828},
pmid = {41616669},
issn = {1873-4111},
abstract = {OBJECTIVE: To investigate the independent and joint effects of leukocyte telomere length and score on the Life's Essential 8 scale on type 2 diabetes mellitus risk using UK Biobank data.
METHODS: A total of 309,288 participants without type 2 diabetes mellitus at baseline were included. Leukocyte telomere length was categorized into quartiles (Q1-Q4), and Life's Essential 8 scores into three groups: low (< 50 points), intermediate (50-79 points) and high (≥ 80 points). Cox proportional-hazards models were used to estimate hazard ratios (HRs) for T2DM. Multiplicative and additive models assessed interactions between leukocyte telomere length and Life's Essential 8 score.
RESULTS: Over a median follow-up of 13.33 years, 9830 participants developed T2DM. Compared with group Q1, the risk of T2DM was reduced by 7% (HR = 0.93, 95%CI: 0.88, 0.99) in the Q4 group. Compared with the low Life's Essential 8 score group, the risk of T2DM was reduced by 70% (HR = 0.30, 95%CI: 0.29, 0.31) and 93% (HR = 0.07, 95%CI: 0.06, 0.08) in the intermediate and high score groups, respectively. The group with long leukocyte telomere length and high Life's Essential 8 score had the most significant reduction in T2DM risk compared with the group with short leukocyte telomere length and low Life's Essential 8 score (HR = 0.07, 95%CI: 0.05, 0.08). Both multiplicative (Pinteraction < 0.001) and additive interactions (S = 1.12, 95%CI: 1.01, 1.25) were observed between the effects of leukocyte telomere length and Life's Essential 8 score on T2DM.
CONCLUSION: Elevated leukocyte telomere length and Life's Essential 8 scores synergistically reduce T2DM risk beyond their individual effects, underscoring the importance of integrated strategies that simultaneously target leukocyte telomere length maintenance and the optimization of cardiovascular-metabolic health in the prevention of T2DM.},
}
RevDate: 2026-01-29
Telomere length associates with regenerative capacity in Brassica napus L.
BMC plant biology pii:10.1186/s12870-026-08215-4 [Epub ahead of print].
Additional Links: PMID-41612180
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PubMed:
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@article {pmid41612180,
year = {2026},
author = {Xie, Q and Du, H and Fang, Y and Zhang, B and Yu, L and Rong, D},
title = {Telomere length associates with regenerative capacity in Brassica napus L.},
journal = {BMC plant biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12870-026-08215-4},
pmid = {41612180},
issn = {1471-2229},
support = {2023JJ30211//Natural Science Foundation of Hunan Province/ ; 2024JJ4018 to D.R.//Natural Science Foundation of Hunan Province/ ; 2024RC3221 to D.R.//Science and Technology Program of Hunan Province/ ; },
}
RevDate: 2026-01-29
CmpDate: 2026-01-29
Omega-3 dietary supplementation combined with exercise to keep telomere integrity in the liver of aged obese female mice.
Journal of physiology and biochemistry, 82(1):5.
Telomere shortening is a key marker of cellular aging and linked to pathologies such as liver disease. Oxidative stress and inflammation (hallmarks of obesity) contribute to telomere shortening, while omega-3 (DHA) and exercise may counteract these effects by enhancing cellular homeostasis. This study aims to analyze the influence of DHA supplementation and/or exercise over one year on liver telomere length in obese aged mice. Two-month-old female mice were fed either a control or high-fat diet (HFD) for four months. Diet-induced obese (DIO) mice were then assigned to one of four groups: (1) DIO, maintained on an HFD; (2) DIO + EX, subjected to exercise; (3) DIO + DHA, fed an HFD supplemented with DHA; and (4) DIO + DHA + EX, subjected to both exercise and DHA supplementation. The intervention continued until the mice reached 18 months of age. The DIO group showed significant telomere attrition, which was prevented only when omega-3 and exercise were combined. Additionally, only the combined DHA and exercise group improved the expression of genes related to oxidative stress (Sirt3, Foxo3, Sod1, Cat). Interestingly, DHA and exercise separately reduced pro-inflammatory cytokine Il-1b expression compared to the control group, but not when combined. These results indicate that DHA combined with physical exercise could be an effective strategy to maintain telomere integrity in aged obese female mice, due to their antioxidant properties.
Additional Links: PMID-41609959
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@article {pmid41609959,
year = {2026},
author = {Gámez-Macías, PE and Félix-Soriano, E and Sáinz, N and Del Moral, AM and García-Calzón, S and Moreno-Aliaga, MJ and González-Muniesa, P},
title = {Omega-3 dietary supplementation combined with exercise to keep telomere integrity in the liver of aged obese female mice.},
journal = {Journal of physiology and biochemistry},
volume = {82},
number = {1},
pages = {5},
pmid = {41609959},
issn = {1877-8755},
mesh = {Animals ; Female ; *Dietary Supplements ; *Liver/metabolism/drug effects/pathology ; *Obesity/metabolism/therapy/pathology/etiology ; *Physical Conditioning, Animal ; Diet, High-Fat/adverse effects ; Mice ; Oxidative Stress/drug effects ; *Fatty Acids, Omega-3/pharmacology/administration & dosage ; *Telomere/metabolism/drug effects ; Mice, Inbred C57BL ; Forkhead Box Protein O3/genetics/metabolism ; Interleukin-1beta/metabolism/genetics ; Sirtuin 3/genetics/metabolism ; Mice, Obese ; *Telomere Shortening/drug effects ; Superoxide Dismutase-1/genetics/metabolism ; Aging ; },
abstract = {Telomere shortening is a key marker of cellular aging and linked to pathologies such as liver disease. Oxidative stress and inflammation (hallmarks of obesity) contribute to telomere shortening, while omega-3 (DHA) and exercise may counteract these effects by enhancing cellular homeostasis. This study aims to analyze the influence of DHA supplementation and/or exercise over one year on liver telomere length in obese aged mice. Two-month-old female mice were fed either a control or high-fat diet (HFD) for four months. Diet-induced obese (DIO) mice were then assigned to one of four groups: (1) DIO, maintained on an HFD; (2) DIO + EX, subjected to exercise; (3) DIO + DHA, fed an HFD supplemented with DHA; and (4) DIO + DHA + EX, subjected to both exercise and DHA supplementation. The intervention continued until the mice reached 18 months of age. The DIO group showed significant telomere attrition, which was prevented only when omega-3 and exercise were combined. Additionally, only the combined DHA and exercise group improved the expression of genes related to oxidative stress (Sirt3, Foxo3, Sod1, Cat). Interestingly, DHA and exercise separately reduced pro-inflammatory cytokine Il-1b expression compared to the control group, but not when combined. These results indicate that DHA combined with physical exercise could be an effective strategy to maintain telomere integrity in aged obese female mice, due to their antioxidant properties.},
}
MeSH Terms:
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Animals
Female
*Dietary Supplements
*Liver/metabolism/drug effects/pathology
*Obesity/metabolism/therapy/pathology/etiology
*Physical Conditioning, Animal
Diet, High-Fat/adverse effects
Mice
Oxidative Stress/drug effects
*Fatty Acids, Omega-3/pharmacology/administration & dosage
*Telomere/metabolism/drug effects
Mice, Inbred C57BL
Forkhead Box Protein O3/genetics/metabolism
Interleukin-1beta/metabolism/genetics
Sirtuin 3/genetics/metabolism
Mice, Obese
*Telomere Shortening/drug effects
Superoxide Dismutase-1/genetics/metabolism
Aging
RevDate: 2026-01-28
Shorter kidney telomeres are associated with nephrosclerosis by an epigenetic signature.
Cardiovascular research pii:8443510 [Epub ahead of print].
AIMS: Ageing leads to a progressive loss in structural integrity and a functional decline of human organs, alongside telomere attrition and alterations in DNA methylation patterns. Their relationships in the human kidney in the context of ageing remain elusive.
METHODS AND RESULTS: We analysed 200 participants from the Human Kidney Tissue Resource (HKTR) with matching information on kidney histology, renal function, blood leukocyte and kidney telomere length, as well as kidney genome-wide DNA methylation profiles. Additional 71 HKTR individuals without telomere data were used in validation analyses. Kidney telomere length showed a significant inverse association with age (β = -0.029, confidence interval = -0.043 to -0.016, P = 0.00003). Shorter kidney telomeres were strongly associated with both renal structure and function, independent of demographic and clinical confounders. Nephrosclerosis score showed a gradual increase with age categories, while kidney telomere length dropped simultaneously. Leukocyte telomere length was not related to the extent of age-related changes in kidney function or structure. Kidney DNA methylation analysis revealed that kidney CpGs, genes, pathways and chromatin patterns associated with kidney telomere length are partly independent of these associated with chronological age. Consisted of 57 CpGs, epigenetic clock of kidney telomere length showed a predictive potential for nephrosclerosis, independent of clinical cofounders, chronological and epigenetic age.
CONCLUSION: Our study revealed that gradual age-related structural involution of human kidney and a decline in its filtration capacity are accompanied by shortening of telomeres in renal cells and that changes in the kidney epigenome (i.e., DNA methylation) may contribute to nephrosclerosis (at least in part) independently of chronological age.
Additional Links: PMID-41604428
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PubMed:
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@article {pmid41604428,
year = {2026},
author = {Akinnibosun, OA and Xu, X and Emmett, A and Nguyen, H and Hames-Fathi, S and Drzal, M and Eales, J and Scannali, D and Prestes, PR and Denniff, M and Bogdanski, P and Zywiec, J and Wystrychowski, W and Zukowska-Szczechowska, E and Guzik, TJ and Samani, NJ and Dormer, J and Tomaszewski, M and Charchar, FJ},
title = {Shorter kidney telomeres are associated with nephrosclerosis by an epigenetic signature.},
journal = {Cardiovascular research},
volume = {},
number = {},
pages = {},
doi = {10.1093/cvr/cvag034},
pmid = {41604428},
issn = {1755-3245},
abstract = {AIMS: Ageing leads to a progressive loss in structural integrity and a functional decline of human organs, alongside telomere attrition and alterations in DNA methylation patterns. Their relationships in the human kidney in the context of ageing remain elusive.
METHODS AND RESULTS: We analysed 200 participants from the Human Kidney Tissue Resource (HKTR) with matching information on kidney histology, renal function, blood leukocyte and kidney telomere length, as well as kidney genome-wide DNA methylation profiles. Additional 71 HKTR individuals without telomere data were used in validation analyses. Kidney telomere length showed a significant inverse association with age (β = -0.029, confidence interval = -0.043 to -0.016, P = 0.00003). Shorter kidney telomeres were strongly associated with both renal structure and function, independent of demographic and clinical confounders. Nephrosclerosis score showed a gradual increase with age categories, while kidney telomere length dropped simultaneously. Leukocyte telomere length was not related to the extent of age-related changes in kidney function or structure. Kidney DNA methylation analysis revealed that kidney CpGs, genes, pathways and chromatin patterns associated with kidney telomere length are partly independent of these associated with chronological age. Consisted of 57 CpGs, epigenetic clock of kidney telomere length showed a predictive potential for nephrosclerosis, independent of clinical cofounders, chronological and epigenetic age.
CONCLUSION: Our study revealed that gradual age-related structural involution of human kidney and a decline in its filtration capacity are accompanied by shortening of telomeres in renal cells and that changes in the kidney epigenome (i.e., DNA methylation) may contribute to nephrosclerosis (at least in part) independently of chronological age.},
}
RevDate: 2026-01-28
CmpDate: 2026-01-28
Telomere-to-Telomere Genome Assembly of Two Hemiculter Species Provide Insights into the Genomic and Morphometric Bases of Adaptation to Flow Velocity.
Biomolecules, 16(1): pii:biom16010083.
Flow velocity is a key environmental factor that exerts multifaceted effects on fish growth and adaptation. Through long-term natural selection, fish have evolved adaptability to specific flow conditions, which not only relate to oxygen supply and food acquisition but also play a decisive role in reproduction, development, and population maintenance. To investigate the genomic mechanisms through which hydrodynamic environments drive divergence in closely related species, we focused on two sister species, Hemiculter bleekeri and Hemiculter leucisculus, which are adapted to contrasting flow regimes. We generated high-quality, chromosome level telomere-to-telomere (T2T) genomes and integrated comparative genomic analyses, we investigated the genetic basis underlying body shape regulation and reproductive strategies, aiming to decipher the adaptive evolutionary patterns of these species in response to differing hydrodynamic conditions from an integrated genotype phenotype perspective. We integrated PacBio HiFi, Hi-C, and Oxford Nanopore Technologies (ONT) ultra-long read sequencing data to construct high-quality T2T reference genomes for both species. The final genome assemblies are 0.998 Gb for H. bleekeri and 1.05 Gb for H. leucisculus, with each species possessing 24 chromosomes and all chromosomal sequences assembled into single contigs. Contig N50 values reached 40.45 Mb and 40.66 Mb, respectively, and both assemblies are gap-free. BUSCO assessments yielded completeness scores of 99.34% for both genomes, confirming their high continuity and accuracy. Integrated morphometric and genomic analyses revealed distinct adaptive strategies in two Hemiculter Species. H. bleekeri has evolved a streamlined body, underpinned by expansions in body shape related genes, and a pelagic egg strategy. In contrast, the adhesive egg strategy of H. leucisculus is supported by expansions in adhesion-related gene families. This divergence reflects adaptation to distinct flow velocity. By combining high-quality chromosome-level T2T genomes with morphometric and comparative genomic approaches, this study establishes a comprehensive framework for understanding the molecular mechanisms underlying adaptive evolution in freshwater fishes inhabiting contrasting flow velocity.
Additional Links: PMID-41594622
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PubMed:
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@article {pmid41594622,
year = {2026},
author = {Liu, J and Yin, D and Ma, F and Jiang, M and Wang, X and Wang, P and Liu, K},
title = {Telomere-to-Telomere Genome Assembly of Two Hemiculter Species Provide Insights into the Genomic and Morphometric Bases of Adaptation to Flow Velocity.},
journal = {Biomolecules},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/biom16010083},
pmid = {41594622},
issn = {2218-273X},
support = {NO.2023TD11//Central Public-interest Scientific Institution Basal Research Fund, CAFS/ ; NO. 2024BFAFZ02936//Monitoring of aquatic resources in key waters of Anhui province Fund/ ; NO. 2024XT1003//Central Public-interest Scientific Institution Basal Research Fund,CAFS/ ; },
mesh = {Animals ; *Telomere/genetics ; *Genome ; *Adaptation, Physiological/genetics ; Genomics ; Hydrodynamics ; },
abstract = {Flow velocity is a key environmental factor that exerts multifaceted effects on fish growth and adaptation. Through long-term natural selection, fish have evolved adaptability to specific flow conditions, which not only relate to oxygen supply and food acquisition but also play a decisive role in reproduction, development, and population maintenance. To investigate the genomic mechanisms through which hydrodynamic environments drive divergence in closely related species, we focused on two sister species, Hemiculter bleekeri and Hemiculter leucisculus, which are adapted to contrasting flow regimes. We generated high-quality, chromosome level telomere-to-telomere (T2T) genomes and integrated comparative genomic analyses, we investigated the genetic basis underlying body shape regulation and reproductive strategies, aiming to decipher the adaptive evolutionary patterns of these species in response to differing hydrodynamic conditions from an integrated genotype phenotype perspective. We integrated PacBio HiFi, Hi-C, and Oxford Nanopore Technologies (ONT) ultra-long read sequencing data to construct high-quality T2T reference genomes for both species. The final genome assemblies are 0.998 Gb for H. bleekeri and 1.05 Gb for H. leucisculus, with each species possessing 24 chromosomes and all chromosomal sequences assembled into single contigs. Contig N50 values reached 40.45 Mb and 40.66 Mb, respectively, and both assemblies are gap-free. BUSCO assessments yielded completeness scores of 99.34% for both genomes, confirming their high continuity and accuracy. Integrated morphometric and genomic analyses revealed distinct adaptive strategies in two Hemiculter Species. H. bleekeri has evolved a streamlined body, underpinned by expansions in body shape related genes, and a pelagic egg strategy. In contrast, the adhesive egg strategy of H. leucisculus is supported by expansions in adhesion-related gene families. This divergence reflects adaptation to distinct flow velocity. By combining high-quality chromosome-level T2T genomes with morphometric and comparative genomic approaches, this study establishes a comprehensive framework for understanding the molecular mechanisms underlying adaptive evolution in freshwater fishes inhabiting contrasting flow velocity.},
}
MeSH Terms:
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Animals
*Telomere/genetics
*Genome
*Adaptation, Physiological/genetics
Genomics
Hydrodynamics
RevDate: 2026-01-26
CmpDate: 2026-01-26
Association Between Telomere Length and Thyrotoxicosis: Insights from a Two-sample Mendelian Randomization Study.
Journal of visualized experiments : JoVE.
Thyrotoxicosis is an endocrine disorder characterized by excess thyroid hormones, yet its etiologic links to systemic aging biology remain incompletely defined. Telomere length (TL) reflects cellular senescence and genome stability and has been implicated in multiple complex diseases. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effect of genetically predicted TL on the risk of thyrotoxicosis. Genetic instruments for TL were derived from a large genome-wide association study (GWAS) of European ancestry (n > 470,000). Thyrotoxicosis summary statistics were obtained from the latest FinnGen release (≈4,000 cases and >210,000 controls). Primary inverse-variance-weighted analyses indicated that longer genetically proxied TL is associated with a lower risk of thyrotoxicosis, and the direction and magnitude of the effect were consistent across complementary estimators (MR-Egger, weighted median/maximum likelihood, MR-PRESSO, and MR-RAPS). Sensitivity analyses showed no evidence of directional pleiotropy, and Cochran's Q was used to assess heterogeneity. A Steiger directionality test supported the causal flow from TL to thyrotoxicosis. To our knowledge, this work is among the first MR analyses to assess the causal relationship between overall thyrotoxicosis risk and TL using contemporary GWAS resources, extending prior evidence focused on hyperthyroidism-related phenotypes. These findings suggest that cellular aging processes indexed by TL may contribute to thyrotoxicosis susceptibility and motivate future longitudinal and mechanistic studies on telomere biology in thyroid dysfunction.
Additional Links: PMID-41587130
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Citation:
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@article {pmid41587130,
year = {2026},
author = {Chu, W and Yu, C and Chu, W and Li, W},
title = {Association Between Telomere Length and Thyrotoxicosis: Insights from a Two-sample Mendelian Randomization Study.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {227},
pages = {},
doi = {10.3791/69618},
pmid = {41587130},
issn = {1940-087X},
mesh = {*Thyrotoxicosis/genetics ; Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study/methods ; *Telomere/genetics ; },
abstract = {Thyrotoxicosis is an endocrine disorder characterized by excess thyroid hormones, yet its etiologic links to systemic aging biology remain incompletely defined. Telomere length (TL) reflects cellular senescence and genome stability and has been implicated in multiple complex diseases. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal effect of genetically predicted TL on the risk of thyrotoxicosis. Genetic instruments for TL were derived from a large genome-wide association study (GWAS) of European ancestry (n > 470,000). Thyrotoxicosis summary statistics were obtained from the latest FinnGen release (≈4,000 cases and >210,000 controls). Primary inverse-variance-weighted analyses indicated that longer genetically proxied TL is associated with a lower risk of thyrotoxicosis, and the direction and magnitude of the effect were consistent across complementary estimators (MR-Egger, weighted median/maximum likelihood, MR-PRESSO, and MR-RAPS). Sensitivity analyses showed no evidence of directional pleiotropy, and Cochran's Q was used to assess heterogeneity. A Steiger directionality test supported the causal flow from TL to thyrotoxicosis. To our knowledge, this work is among the first MR analyses to assess the causal relationship between overall thyrotoxicosis risk and TL using contemporary GWAS resources, extending prior evidence focused on hyperthyroidism-related phenotypes. These findings suggest that cellular aging processes indexed by TL may contribute to thyrotoxicosis susceptibility and motivate future longitudinal and mechanistic studies on telomere biology in thyroid dysfunction.},
}
MeSH Terms:
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hide MeSH Terms
*Thyrotoxicosis/genetics
Humans
*Mendelian Randomization Analysis/methods
Genome-Wide Association Study/methods
*Telomere/genetics
RevDate: 2026-01-28
CmpDate: 2026-01-26
Associations between leukocyte telomere length and three measures of folate status: a cross-sectional analysis of NHANES 1999-2002.
Frontiers in nutrition, 12:1714482.
BACKGROUND: Shortening of leukocyte telomere length (LTL) is a core hallmark of cellular senescence. Folate provides essential methyl groups for DNA synthesis and repair, theoretically capable of slowing telomere attrition by maintaining genomic integrity. However, current epidemiological studies on folate and LTL are still limited, and most prior investigations have relied on a single metric of folate status.
OBJECTIVE: This study aimed to investigate the associations between LTL and three measures of folate status, dietary intake, serum folate and red blood cell (RBC) folate, to provide more precise epidemiological evidence of folate's role in cellular aging and to establish a scientific basis for potential nutritional intervention strategies.
METHODS: This cross-sectional analysis included 7,324 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Multivariable linear regression models, adjusted for demographic, lifestyle, and nutritional factors, were used to assess associations. Restricted cubic splines and piecewise linear regression were employed to evaluate non-linear relationships.
RESULTS: After full adjustment, both serum and RBC folate showed positive linear associations with longer LTL (P for trend < 0.05). Dietary folate exhibited a non-linear relationship with LTL (P for non-linearity < 0.05). Meeting the recommended intake (≥400 μg/day) was associated with longer telomeres (β = 0.05, 95% CI: 0.03-0.06). A saturation effect was observed; beyond 500.86 μg/day (95% CI: 490.71-511.01), further intake did not significantly increase LTL.
CONCLUSION: Adequate folate status is associated with longer telomeres, supporting a role in mitigating cellular aging. Dietary intake ≥400 μg/day is beneficial, but exceeding ~500 μg/day offers no further advantage.
Additional Links: PMID-41586235
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Citation:
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@article {pmid41586235,
year = {2025},
author = {Xue, Q and Chen, H},
title = {Associations between leukocyte telomere length and three measures of folate status: a cross-sectional analysis of NHANES 1999-2002.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1714482},
pmid = {41586235},
issn = {2296-861X},
abstract = {BACKGROUND: Shortening of leukocyte telomere length (LTL) is a core hallmark of cellular senescence. Folate provides essential methyl groups for DNA synthesis and repair, theoretically capable of slowing telomere attrition by maintaining genomic integrity. However, current epidemiological studies on folate and LTL are still limited, and most prior investigations have relied on a single metric of folate status.
OBJECTIVE: This study aimed to investigate the associations between LTL and three measures of folate status, dietary intake, serum folate and red blood cell (RBC) folate, to provide more precise epidemiological evidence of folate's role in cellular aging and to establish a scientific basis for potential nutritional intervention strategies.
METHODS: This cross-sectional analysis included 7,324 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Multivariable linear regression models, adjusted for demographic, lifestyle, and nutritional factors, were used to assess associations. Restricted cubic splines and piecewise linear regression were employed to evaluate non-linear relationships.
RESULTS: After full adjustment, both serum and RBC folate showed positive linear associations with longer LTL (P for trend < 0.05). Dietary folate exhibited a non-linear relationship with LTL (P for non-linearity < 0.05). Meeting the recommended intake (≥400 μg/day) was associated with longer telomeres (β = 0.05, 95% CI: 0.03-0.06). A saturation effect was observed; beyond 500.86 μg/day (95% CI: 490.71-511.01), further intake did not significantly increase LTL.
CONCLUSION: Adequate folate status is associated with longer telomeres, supporting a role in mitigating cellular aging. Dietary intake ≥400 μg/day is beneficial, but exceeding ~500 μg/day offers no further advantage.},
}
RevDate: 2026-01-28
CmpDate: 2026-01-26
Global research landscape of telomere biology in infectious diseases: mechanistic links between host-pathogen interactions and immune ageing.
Frontiers in aging, 6:1729868.
Telomeres, nucleoprotein structures located at the ends of chromosomes, maintain genomic stability and regulate cellular lifespan, particularly in immune cells. Telomere shortening, driven by cell division and limited telomerase activity, accelerates immune ageing and increases susceptibility to infectious diseases. Chronic infections like HIV and tuberculosis exacerbate telomere attrition through sustained immune activation and oxidative stress. This study presents a bibliometric review of research on telomere length and infectious diseases from 2005 to 2025. Data from the Web of Science Core Collection were analysed using VOSviewer and CiteSpace, software tools for visualising co-authorship, citation, and keyword networks, to assess publication trends, collaborations, and themes. A total of 123 publications were identified, showing steady growth with a 60% increase in publications from 2020 to 2022 during the COVID-19 pandemic. Leading journals included Frontiers in Immunology, PLoS ONE, and Scientific Reports. The United States produced the largest share of publications, followed by Canada and Spain, with notable contributions from the University of British Columbia and Université de Montréal. Influential authors such as Côté HCF, Pick N, and Maan EJ have advanced research, particularly in the areas of HIV and tuberculosis. Keyword analysis highlighted two dominant themes: immune ageing and infection-related stress. Malaria research was comparatively scarce, underscoring a gap for future investigation. These findings inform future research on telomere-targeted interventions and epidemiological studies aimed at enhancing infectious disease management. This review provides a comprehensive overview of the field's progress and identifies key areas for future investigation.
Additional Links: PMID-41585361
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@article {pmid41585361,
year = {2025},
author = {Wakai, TN and Yensii, NG and Kernyuy, FB and Bella-Omunagbe, M and Chinedu, SN and Afolabi, IS},
title = {Global research landscape of telomere biology in infectious diseases: mechanistic links between host-pathogen interactions and immune ageing.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1729868},
pmid = {41585361},
issn = {2673-6217},
abstract = {Telomeres, nucleoprotein structures located at the ends of chromosomes, maintain genomic stability and regulate cellular lifespan, particularly in immune cells. Telomere shortening, driven by cell division and limited telomerase activity, accelerates immune ageing and increases susceptibility to infectious diseases. Chronic infections like HIV and tuberculosis exacerbate telomere attrition through sustained immune activation and oxidative stress. This study presents a bibliometric review of research on telomere length and infectious diseases from 2005 to 2025. Data from the Web of Science Core Collection were analysed using VOSviewer and CiteSpace, software tools for visualising co-authorship, citation, and keyword networks, to assess publication trends, collaborations, and themes. A total of 123 publications were identified, showing steady growth with a 60% increase in publications from 2020 to 2022 during the COVID-19 pandemic. Leading journals included Frontiers in Immunology, PLoS ONE, and Scientific Reports. The United States produced the largest share of publications, followed by Canada and Spain, with notable contributions from the University of British Columbia and Université de Montréal. Influential authors such as Côté HCF, Pick N, and Maan EJ have advanced research, particularly in the areas of HIV and tuberculosis. Keyword analysis highlighted two dominant themes: immune ageing and infection-related stress. Malaria research was comparatively scarce, underscoring a gap for future investigation. These findings inform future research on telomere-targeted interventions and epidemiological studies aimed at enhancing infectious disease management. This review provides a comprehensive overview of the field's progress and identifies key areas for future investigation.},
}
RevDate: 2026-01-28
CmpDate: 2026-01-26
Small adipose-derived mesenchymal stromal cells exhibit longer telomeres and enhanced regenerative potential.
Frontiers in bioengineering and biotechnology, 13:1687461.
Younger, replicative cells with longer telomeres can enhance regenerative therapies, however, there is a lack of a standard method to assess telomere length in live cells. The present study investigated whether the relative size of human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) can influence their telomere length. During early culture, a smaller-sized AD-MSC subpopulation was identified based on characteristic colony emergence. Telomere lengths in total and smaller-sized cell populations were measured. Polymerase chain reaction revealed expression of Nanog and OCT3/4 in small-sized AD-MSCs. Their safety was evaluated in immunodeficient BALB/c nude mice. Smaller AD-MSCs revealed distinct growth properties, with the cell monolayer rolling up into a large aggregate. These cells had longer telomeres (18,121.43 base pairs [bp]) than the total population (15,870.44 bp) and formed teratoma-like structures with skin-like morphology (including hair). In conclusion, AD-MSC size reliably isolates cells with longer telomeres and potential.
Additional Links: PMID-41582951
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Citation:
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@article {pmid41582951,
year = {2025},
author = {Berzins, U and Baronins, J and Sorokins, H and Goel, S and Shishkin, A and Zvirgzdina, R and Rautmane, A and Minchev, D},
title = {Small adipose-derived mesenchymal stromal cells exhibit longer telomeres and enhanced regenerative potential.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1687461},
pmid = {41582951},
issn = {2296-4185},
abstract = {Younger, replicative cells with longer telomeres can enhance regenerative therapies, however, there is a lack of a standard method to assess telomere length in live cells. The present study investigated whether the relative size of human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) can influence their telomere length. During early culture, a smaller-sized AD-MSC subpopulation was identified based on characteristic colony emergence. Telomere lengths in total and smaller-sized cell populations were measured. Polymerase chain reaction revealed expression of Nanog and OCT3/4 in small-sized AD-MSCs. Their safety was evaluated in immunodeficient BALB/c nude mice. Smaller AD-MSCs revealed distinct growth properties, with the cell monolayer rolling up into a large aggregate. These cells had longer telomeres (18,121.43 base pairs [bp]) than the total population (15,870.44 bp) and formed teratoma-like structures with skin-like morphology (including hair). In conclusion, AD-MSC size reliably isolates cells with longer telomeres and potential.},
}
RevDate: 2026-01-26
T-Cell "Rejuvenation" Nanovaccine: Enhancing Immunological Memory and Antitumor Responses through Telomere Extension.
Journal of the American Chemical Society [Epub ahead of print].
Replicative senescence in immune cells undermines vaccine efficacy, with telomere attrition recognized as a key factor to cellular senescence. Studies have shown that the extracellular vesicles (EVs) of bone marrow-derived dendritic cells (BMDCs), which contain the telomeric compounds, can promote telomerase-independent T-cell telomere extension via telomere transfer. Based on this mechanism, we designed a long-term memory T-cell vaccine (LMT/OT-II), which is composed of EVs from BMDCs carrying the ovalbumin peptide OT-II. This vaccine not only enhances antigen presentation but also extends T-cell telomere length, enhancing T-cell vitality and restoring youthful characteristics. To further enhance the antitumor effects, we incorporated the immune adjuvant Poly(I:C) to activate T cells. In both young and aged mouse models, the LMT/OT-II + Poly(I:C) effectively suppressed the growth of B16-OVA melanoma and significantly prolonged the survival of the mouse models. We further developed the LMT/Adpgk + Poly(I:C) vaccine based on mouse colon cancer cell (MC38) neoantigen peptide, which also showed promising results in mice. Through telomere transfer to restore T-cell function and enhance immune memory, our study provides a novel and universal strategy for developing more effective and durable T-cell vaccines, particularly for diseases associated with immunosenescence.
Additional Links: PMID-41582446
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PubMed:
Citation:
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@article {pmid41582446,
year = {2026},
author = {Cao, X and Zeng, T and Bai, S and Li, S and Liu, Y and Fang, L and Fang, X and Chen, Q and Lu, C and Yang, H},
title = {T-Cell "Rejuvenation" Nanovaccine: Enhancing Immunological Memory and Antitumor Responses through Telomere Extension.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c21977},
pmid = {41582446},
issn = {1520-5126},
abstract = {Replicative senescence in immune cells undermines vaccine efficacy, with telomere attrition recognized as a key factor to cellular senescence. Studies have shown that the extracellular vesicles (EVs) of bone marrow-derived dendritic cells (BMDCs), which contain the telomeric compounds, can promote telomerase-independent T-cell telomere extension via telomere transfer. Based on this mechanism, we designed a long-term memory T-cell vaccine (LMT/OT-II), which is composed of EVs from BMDCs carrying the ovalbumin peptide OT-II. This vaccine not only enhances antigen presentation but also extends T-cell telomere length, enhancing T-cell vitality and restoring youthful characteristics. To further enhance the antitumor effects, we incorporated the immune adjuvant Poly(I:C) to activate T cells. In both young and aged mouse models, the LMT/OT-II + Poly(I:C) effectively suppressed the growth of B16-OVA melanoma and significantly prolonged the survival of the mouse models. We further developed the LMT/Adpgk + Poly(I:C) vaccine based on mouse colon cancer cell (MC38) neoantigen peptide, which also showed promising results in mice. Through telomere transfer to restore T-cell function and enhance immune memory, our study provides a novel and universal strategy for developing more effective and durable T-cell vaccines, particularly for diseases associated with immunosenescence.},
}
RevDate: 2026-01-25
Accelerated senescence in sulfur mustard-exposed individuals: Evidence from oxidative DNA damage, telomere shortening, and dietary inflammatory index.
Ecotoxicology and environmental safety, 310:119722 pii:S0147-6513(26)00051-5 [Epub ahead of print].
Sulfur mustard (SM) exposure induces respiratory complications, known as "mustard lung (ML)" through oxidative stress and chronic inflammation. This study investigated premature cellular senescence as a marker of systemic aging in SM-exposed veterans with serious pulmonary conditions, focusing on oxidative stress, DNA damage, telomere shortening, and OGG1/p16 gene expression, as well as the role of pro-inflammatory dietary patterns measured by the Dietary Inflammatory Index (DII). The study included SM-exposed veterans and healthy controls. Veterans were clinically categorized based on severity and resemblance to chronic bronchitis (CB), bronchial obliterans (BO), or asthma. Leukocyte telomere length (LTL) was assessed using MMqPCR, oxidative DNA damage (8-oxo-dG) via ELISA, and OGG1/p16 gene expression by q-PCR. DII was calculated from dietary intake data. Compared to controls, SM-exposed veterans exhibited shorter telomeres, higher p16 expression, elevated 8-oxo-dG levels, and upregulated OGG1 expression, reflecting accelerated aging and oxidative DNA damage. Asthma, BO, and CB-like subgroups shared similar trends, with variations in oxidative damage and telomere shortening. The ML group had higher DII scores correlated with shorter telomeres and increased p16 expression. These findings suggest that SM exposure, coupled with pro-inflammatory dietary patterns, accelerates cellular aging through oxidative damage and inflammation. Markers such as telomere shortening, OGG1, and p16 expression signify SM-induced damage, while 8-oxo-dG levels can indicate disease severity. In addition, variations in 8-oxo-dG levels and telomere shortening can assist in distinguishing between corresponding asthma, BO, and CB. Ultimately, this study underscores the importance of targeted interventions, including dietary modifications, to mitigate the long-term effects of SM exposure and improve outcomes for affected individuals.
Additional Links: PMID-41581471
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@article {pmid41581471,
year = {2026},
author = {Vaez-Mahdavi, MR and Jamali, T and Behboudi, H and Homayounfar, R and Mojtahed, M and Ghazanfari, T and Ardestani, SK},
title = {Accelerated senescence in sulfur mustard-exposed individuals: Evidence from oxidative DNA damage, telomere shortening, and dietary inflammatory index.},
journal = {Ecotoxicology and environmental safety},
volume = {310},
number = {},
pages = {119722},
doi = {10.1016/j.ecoenv.2026.119722},
pmid = {41581471},
issn = {1090-2414},
abstract = {Sulfur mustard (SM) exposure induces respiratory complications, known as "mustard lung (ML)" through oxidative stress and chronic inflammation. This study investigated premature cellular senescence as a marker of systemic aging in SM-exposed veterans with serious pulmonary conditions, focusing on oxidative stress, DNA damage, telomere shortening, and OGG1/p16 gene expression, as well as the role of pro-inflammatory dietary patterns measured by the Dietary Inflammatory Index (DII). The study included SM-exposed veterans and healthy controls. Veterans were clinically categorized based on severity and resemblance to chronic bronchitis (CB), bronchial obliterans (BO), or asthma. Leukocyte telomere length (LTL) was assessed using MMqPCR, oxidative DNA damage (8-oxo-dG) via ELISA, and OGG1/p16 gene expression by q-PCR. DII was calculated from dietary intake data. Compared to controls, SM-exposed veterans exhibited shorter telomeres, higher p16 expression, elevated 8-oxo-dG levels, and upregulated OGG1 expression, reflecting accelerated aging and oxidative DNA damage. Asthma, BO, and CB-like subgroups shared similar trends, with variations in oxidative damage and telomere shortening. The ML group had higher DII scores correlated with shorter telomeres and increased p16 expression. These findings suggest that SM exposure, coupled with pro-inflammatory dietary patterns, accelerates cellular aging through oxidative damage and inflammation. Markers such as telomere shortening, OGG1, and p16 expression signify SM-induced damage, while 8-oxo-dG levels can indicate disease severity. In addition, variations in 8-oxo-dG levels and telomere shortening can assist in distinguishing between corresponding asthma, BO, and CB. Ultimately, this study underscores the importance of targeted interventions, including dietary modifications, to mitigate the long-term effects of SM exposure and improve outcomes for affected individuals.},
}
RevDate: 2026-01-24
Accelerated epigenetic aging and shorter DNA methylation-based telomere length in sarcopenic obesity: an exploratory pilot study.
Epigenomics [Epub ahead of print].
BACKGROUND: Sarcopenic obesity (SO), defined as the coexistence of excess fat mass and low muscle mass/function, has been linked to adverse outcomes. Epigenetic alterations are central hallmarks of aging. Evaluating how obesity, sarcopenia, and SO are related to epigenetic aging biomarkers may provide insights into cellular aging and disease risk.
METHODS: In this cross-sectional study, 30 older women were classified into the control, obesity, sarcopenia, and SO groups and underwent anthropometry measurements, body composition analysis, and handgrip strength. Blood DNA methylation (DNAm) biomarkers were used to estimate eight epigenetic clocks (Horvath, Hannum, DNAmTL, PhenoAge, GrimAge, GrimAge2, Zhang, and FitAge) and to calculate intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA). Associations were tested with Bayesian linear and quantile regressions, adjusted for age and HOMA-IR.
RESULTS: SO was associated with higher EEAA, DNAmFitAge, and Hannum clock estimates, and shorter DNAmTL in both models. Obesity showed positive associations with these clocks in adjusted models and higher quantiles.
CONCLUSIONS: SO is associated with accelerated aging and shorter DNAmTL. Obesity contributes to biological aging, whereas sarcopenia without obesity does not. These findings suggest that excess adiposity combined with low muscle mass may worsen age-related decline, although the small sample size should be considered.
Additional Links: PMID-41578880
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@article {pmid41578880,
year = {2026},
author = {Rossini Venturini, AC and Fogagnolo, C and Ortiz, GU and da Silva Rodrigues, G and da Silva, AP and Noronha, NY and Abud, GF and Silva, BM and Benzoni, GG and de Souza Pinhel, MA and Watanabe, LM and Sae-Lee, C and Travieso, SG and de Lima Viliod, MC and Nonino, CB and da Silva, ASR and de Freitas, EC},
title = {Accelerated epigenetic aging and shorter DNA methylation-based telomere length in sarcopenic obesity: an exploratory pilot study.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/17501911.2026.2617179},
pmid = {41578880},
issn = {1750-192X},
abstract = {BACKGROUND: Sarcopenic obesity (SO), defined as the coexistence of excess fat mass and low muscle mass/function, has been linked to adverse outcomes. Epigenetic alterations are central hallmarks of aging. Evaluating how obesity, sarcopenia, and SO are related to epigenetic aging biomarkers may provide insights into cellular aging and disease risk.
METHODS: In this cross-sectional study, 30 older women were classified into the control, obesity, sarcopenia, and SO groups and underwent anthropometry measurements, body composition analysis, and handgrip strength. Blood DNA methylation (DNAm) biomarkers were used to estimate eight epigenetic clocks (Horvath, Hannum, DNAmTL, PhenoAge, GrimAge, GrimAge2, Zhang, and FitAge) and to calculate intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA). Associations were tested with Bayesian linear and quantile regressions, adjusted for age and HOMA-IR.
RESULTS: SO was associated with higher EEAA, DNAmFitAge, and Hannum clock estimates, and shorter DNAmTL in both models. Obesity showed positive associations with these clocks in adjusted models and higher quantiles.
CONCLUSIONS: SO is associated with accelerated aging and shorter DNAmTL. Obesity contributes to biological aging, whereas sarcopenia without obesity does not. These findings suggest that excess adiposity combined with low muscle mass may worsen age-related decline, although the small sample size should be considered.},
}
RevDate: 2026-01-23
Alternative Lengthening of Telomeres in Malignant PEComas: Correlation with Molecular Features Including ATRX Gene Mutation Status.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:S0893-3952(26)00007-4 [Epub ahead of print].
A subset of perivascular epithelioid cell neoplasms (PEComas) is histologically malignant and at high risk for metastasis, and there is limited literature available on the genetic features of these lesions. In addition to driver alterations in the TSC/mTOR pathway or TFE3 fusions, recurrent ATRX mutations have been identified in malignant PEComas. ATRX mutations have been tightly associated with the Alternative Lengthening of Telomeres (ALT) phenotype in a variety of other tumor types. Whether malignant PEComas - regardless of ATRX mutational status - harbor the ALT phenotype has not been characterized. We conducted immunohistochemistry (IHC), next-generation sequencing (NGS), and telomere-specific fluorescence in situ hybridization (FISH) on a cohort of 32 malignant PEComas to evaluate for the ALT phenotype and to correlate with underlying genomic features. TSC1/2/mTOR/RICTOR mutations or TFE3 translocations were detected in 16/31 cases (52%) by NGS. Recurrent ATRX alterations were identified in 10 cases (32%). Sixteen cases underwent ALT FISH, 8 of which harbored ATRX alterations by NGS and/or ATRX loss by IHC, and 8 cases without detectable ATRX alterations by NGS or loss by IHC. 12 of these 16 cases demonstrated the ALT phenotype by FISH (75%). All 8 cases with ATRX mutations were ALT positive by FISH (100%). In 8 cases without ATRX alterations by NGS, 4 cases demonstrated ALT by FISH (50%). Of these 4 ALT-positive cases lacking ATRX genomic alterations, IHC revealed ATRX protein loss in 1 case. Overall, ATRX alterations were identified in 75% of ALT-positive tumors. Our study provides the first correlation between ALT and genomic features of malignant PEComas, demonstrating that ATRX alterations invariably predict ALT, but that a subset of tumors without mutations in known ALT suppressor genes also activate ALT. These findings confirm that the association between ATRX alterations and ALT observed in other tumor types applies to PEComas and indicate that in a subset of cases, ALT may be activated by ATRX independent mechanisms.
Additional Links: PMID-41577032
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@article {pmid41577032,
year = {2026},
author = {Lin, R and Gross, JM and Xing, D and Argani, P and Lotan, T and Meeker, AK and Baraban, E},
title = {Alternative Lengthening of Telomeres in Malignant PEComas: Correlation with Molecular Features Including ATRX Gene Mutation Status.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100964},
doi = {10.1016/j.modpat.2026.100964},
pmid = {41577032},
issn = {1530-0285},
abstract = {A subset of perivascular epithelioid cell neoplasms (PEComas) is histologically malignant and at high risk for metastasis, and there is limited literature available on the genetic features of these lesions. In addition to driver alterations in the TSC/mTOR pathway or TFE3 fusions, recurrent ATRX mutations have been identified in malignant PEComas. ATRX mutations have been tightly associated with the Alternative Lengthening of Telomeres (ALT) phenotype in a variety of other tumor types. Whether malignant PEComas - regardless of ATRX mutational status - harbor the ALT phenotype has not been characterized. We conducted immunohistochemistry (IHC), next-generation sequencing (NGS), and telomere-specific fluorescence in situ hybridization (FISH) on a cohort of 32 malignant PEComas to evaluate for the ALT phenotype and to correlate with underlying genomic features. TSC1/2/mTOR/RICTOR mutations or TFE3 translocations were detected in 16/31 cases (52%) by NGS. Recurrent ATRX alterations were identified in 10 cases (32%). Sixteen cases underwent ALT FISH, 8 of which harbored ATRX alterations by NGS and/or ATRX loss by IHC, and 8 cases without detectable ATRX alterations by NGS or loss by IHC. 12 of these 16 cases demonstrated the ALT phenotype by FISH (75%). All 8 cases with ATRX mutations were ALT positive by FISH (100%). In 8 cases without ATRX alterations by NGS, 4 cases demonstrated ALT by FISH (50%). Of these 4 ALT-positive cases lacking ATRX genomic alterations, IHC revealed ATRX protein loss in 1 case. Overall, ATRX alterations were identified in 75% of ALT-positive tumors. Our study provides the first correlation between ALT and genomic features of malignant PEComas, demonstrating that ATRX alterations invariably predict ALT, but that a subset of tumors without mutations in known ALT suppressor genes also activate ALT. These findings confirm that the association between ATRX alterations and ALT observed in other tumor types applies to PEComas and indicate that in a subset of cases, ALT may be activated by ATRX independent mechanisms.},
}
RevDate: 2026-01-23
Proteomics method for identifying POT1-associated complexes at telomeres using ChIP-Mass spectrometry.
Methods (San Diego, Calif.) pii:S1046-2023(26)00007-1 [Epub ahead of print].
POT1 is the only single stranded telomere binding protein in the shelterin complex. Together with TPP1, POT1 plays a crucial role in regulating telomere length and protecting telomeres from DNA damage repair proteins. The activation of DNA damage repair proteins at telomeres can be detrimental to cells, so their activity must be suppressed. POT1 interacts with other telomeric proteins (TRF2, TRF1, TIN2 and RAP1) via its association with TPP1. These proteins function together to protect and maintain the telomeres. Despite extensive knowledge of POT1's role within the shelterin complex, the full spectrum of its interactors at the single-stranded telomeric overhang remains poorly defined. To study these interactions, we generated an endogenous Flag-tag knock-in of POT1 using the CRISPR-Cas9 gene editing system. To address the risk of unintended gene disruption associated with this technique, we conducted an in-depth characterization of the endogenously Flag-tagged POT1 clone to ensure that its telomere and TPP1 binding functions remained intact. Further, we performed proteomic profiling of the Flag-tagged POT1 within the chromatin fraction using ChIP-MS to explore its proteome. Our analysis uncovered a novel set of POT1-associated proteins at the extremes of telomeres. Given that POT1 exclusively binds to the single-stranded 3' overhang of telomeres, the proteomic data obtained indicates POT1 interactions occurring at the extreme ends of telomeres. In conclusion, our study reveals previously uncharacterized POT1 associated proteins using ChIP mass spectrometric approach, paving the way for further investigations into telomere biology and potential therapies targeting telomere regulation.
Additional Links: PMID-41577003
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@article {pmid41577003,
year = {2026},
author = {Zade, NH and Jain, M and Garg, M and Checker, R and Ghosh, A and Khattar, E},
title = {Proteomics method for identifying POT1-associated complexes at telomeres using ChIP-Mass spectrometry.},
journal = {Methods (San Diego, Calif.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymeth.2026.01.007},
pmid = {41577003},
issn = {1095-9130},
abstract = {POT1 is the only single stranded telomere binding protein in the shelterin complex. Together with TPP1, POT1 plays a crucial role in regulating telomere length and protecting telomeres from DNA damage repair proteins. The activation of DNA damage repair proteins at telomeres can be detrimental to cells, so their activity must be suppressed. POT1 interacts with other telomeric proteins (TRF2, TRF1, TIN2 and RAP1) via its association with TPP1. These proteins function together to protect and maintain the telomeres. Despite extensive knowledge of POT1's role within the shelterin complex, the full spectrum of its interactors at the single-stranded telomeric overhang remains poorly defined. To study these interactions, we generated an endogenous Flag-tag knock-in of POT1 using the CRISPR-Cas9 gene editing system. To address the risk of unintended gene disruption associated with this technique, we conducted an in-depth characterization of the endogenously Flag-tagged POT1 clone to ensure that its telomere and TPP1 binding functions remained intact. Further, we performed proteomic profiling of the Flag-tagged POT1 within the chromatin fraction using ChIP-MS to explore its proteome. Our analysis uncovered a novel set of POT1-associated proteins at the extremes of telomeres. Given that POT1 exclusively binds to the single-stranded 3' overhang of telomeres, the proteomic data obtained indicates POT1 interactions occurring at the extreme ends of telomeres. In conclusion, our study reveals previously uncharacterized POT1 associated proteins using ChIP mass spectrometric approach, paving the way for further investigations into telomere biology and potential therapies targeting telomere regulation.},
}
RevDate: 2026-01-23
CmpDate: 2026-01-23
Telomere length changes during genome-wide epigenetic reprogramming in human preimplantation embryos.
Reproduction (Cambridge, England), 171(1):.
We report on the telomere length (TL) changes in metaphase chromosomes throughout preimplantation development of human embryos-a period of genome-wide epigenetic reprogramming. Using semiquantitative fluorescence in situ hybridization, we measured relative TLs in the metaphase chromosomes of 69 preimplantation embryos from the zygote up to and including the blastocyst stage. Relative TLs increased significantly from zygote to the 2-5-cell stage, remained almost unchanged at the stages of 2-5 and 6-12-cells and decreased by the blastocyst stage. Concurrently with relative TL decrease at the blastocyst stage, an increase in interindividual TL variability occurred. The zygote-inherited, but not newly synthesized chromatids maintained parent-specific telomeres (longer in paternal compared to maternal chromosomes) up to and including the 2-5-cell stage, with a follow-up TL equalization in 6-12-cell embryos. The extent of interchromatid TL asymmetry-a phenomenon potentially linked to telomere lengthening through recombination-was assessed by TL ratios between sister chromatids and showed similar patterns across all stages of preimplantation development. The longer telomere is presumably located in the highly hydroxymethylated sister chromatid of hemihydroxymethylated chromosomes, i.e., those having higher 5-hydroxymethylcytosine content in one sister chromatid than in the other due to global epigenetic reprogramming in early embryogenesis. To conclude, our study suggests that in human preimplantation development telomeres are reprogrammed in conjunction with genome-wide epigenetic reprogramming of an embryo. By the blastocyst stage, when epigenetic reprogramming comes to an end, parent-specific TLs are also completely reprogrammed and every embryo develops its own unique TL pattern.
Additional Links: PMID-41575151
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@article {pmid41575151,
year = {2026},
author = {Krapivin, MI and Pendina, AA and Komarova, EM and Tikhonov, AV and Trusova, ED and Staroverov, DA and Pashkova, EP and Golubeva, AV and Sagurova, YM and Efimova, OA},
title = {Telomere length changes during genome-wide epigenetic reprogramming in human preimplantation embryos.},
journal = {Reproduction (Cambridge, England)},
volume = {171},
number = {1},
pages = {},
doi = {10.1093/reprod/xaaf005},
pmid = {41575151},
issn = {1741-7899},
support = {//Russian Science Foundation/ ; },
mesh = {Humans ; *Blastocyst/metabolism/cytology ; *Epigenesis, Genetic ; *Telomere/genetics ; Female ; *Telomere Homeostasis ; *Embryonic Development/genetics ; *Cellular Reprogramming/genetics ; Male ; In Situ Hybridization, Fluorescence ; *Genome, Human ; },
abstract = {We report on the telomere length (TL) changes in metaphase chromosomes throughout preimplantation development of human embryos-a period of genome-wide epigenetic reprogramming. Using semiquantitative fluorescence in situ hybridization, we measured relative TLs in the metaphase chromosomes of 69 preimplantation embryos from the zygote up to and including the blastocyst stage. Relative TLs increased significantly from zygote to the 2-5-cell stage, remained almost unchanged at the stages of 2-5 and 6-12-cells and decreased by the blastocyst stage. Concurrently with relative TL decrease at the blastocyst stage, an increase in interindividual TL variability occurred. The zygote-inherited, but not newly synthesized chromatids maintained parent-specific telomeres (longer in paternal compared to maternal chromosomes) up to and including the 2-5-cell stage, with a follow-up TL equalization in 6-12-cell embryos. The extent of interchromatid TL asymmetry-a phenomenon potentially linked to telomere lengthening through recombination-was assessed by TL ratios between sister chromatids and showed similar patterns across all stages of preimplantation development. The longer telomere is presumably located in the highly hydroxymethylated sister chromatid of hemihydroxymethylated chromosomes, i.e., those having higher 5-hydroxymethylcytosine content in one sister chromatid than in the other due to global epigenetic reprogramming in early embryogenesis. To conclude, our study suggests that in human preimplantation development telomeres are reprogrammed in conjunction with genome-wide epigenetic reprogramming of an embryo. By the blastocyst stage, when epigenetic reprogramming comes to an end, parent-specific TLs are also completely reprogrammed and every embryo develops its own unique TL pattern.},
}
MeSH Terms:
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Humans
*Blastocyst/metabolism/cytology
*Epigenesis, Genetic
*Telomere/genetics
Female
*Telomere Homeostasis
*Embryonic Development/genetics
*Cellular Reprogramming/genetics
Male
In Situ Hybridization, Fluorescence
*Genome, Human
RevDate: 2026-01-23
Exploring the synergy between telomere length and genomic complexity in CLL.
British journal of haematology [Epub ahead of print].
Additional Links: PMID-41574981
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@article {pmid41574981,
year = {2026},
author = {Ramos-Campoy, S and Puiggros, A and Kamaso, J and Parker, H and Rigolin, GM and Haferlach, C and Larráyoz, MJ and Collado, R and Salgado, R and Calasanz, MJ and Etter, L and Valiente, A and Abrisqueta, P and Bosch, F and Gimeno, E and Cuneo, A and Nguyen-Khac, F and Schoumans, J and Strefford, JC and Espinet, B},
title = {Exploring the synergy between telomere length and genomic complexity in CLL.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70317},
pmid = {41574981},
issn = {1365-2141},
}
RevDate: 2026-01-23
Cytopenia, Hypocellular Bone Marrow, and Shortened Telomere Length Beyond Biallelic Telomere Biology Gene Mutations.
Additional Links: PMID-41574636
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@article {pmid41574636,
year = {2026},
author = {Franco, G and Bruno, LP and Alviano, AM and Vankann, L and Brümmendorf, T and Guerra, F and Vendemini, F and Faverio, P and L'Imperio, V and Cazzaniga, G and Luppi, F and Biondi, A and Balduzzi, A and Beier, F and Saettini, F},
title = {Cytopenia, Hypocellular Bone Marrow, and Shortened Telomere Length Beyond Biallelic Telomere Biology Gene Mutations.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e70150},
doi = {10.1002/1545-5017.70150},
pmid = {41574636},
issn = {1545-5017},
}
RevDate: 2026-01-22
Telomere-to-telomere gap-free genome assembly of the Opsariichthys evolans (Cypriniformes: Cyprinidae).
Scientific data pii:10.1038/s41597-026-06588-7 [Epub ahead of print].
Opsariichthys evolans is a stream-dwelling fish species endemic to China, with its primary distribution encompassing southeastern China and Taiwan. Initially classified under the genus Zacco, it was later reclassified into the genus Opsariichthys based primarily on mitochondrial DNA evidence. However, this taxonomic revision remains partially inconclusive due to the absence of whole-genome data. Therefore, we assembled a telomere-to-telomere, gap-free genome assembly of O. evolans, consisting of 39 chromosomes with one contiguous sequence per chromosome. The assembly had a total size of 886.9 Mb and a contig N50 of 25.44 Mb. The presence of the telomere repeat was clearly confirmed in the genome. BUSCO assessment confirmed 99.34% genome completeness. Collinearity analysis revealed high synteny between O. evolans, O. bidens and Zacco platypus. Genomic comparisons revealed key candidate genes and related biological pathways potentially responsible for color patterning and hydrodynamic adaptation. The complete O. evolans genome provides insights into its genome structure and function, and supports the taxonomic reclassification between the genera Opsariichthys and Zacco.
Additional Links: PMID-41571710
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@article {pmid41571710,
year = {2026},
author = {Wang, P and Wang, X and Yin, D and Liu, J and Jiang, M and Liu, K},
title = {Telomere-to-telomere gap-free genome assembly of the Opsariichthys evolans (Cypriniformes: Cyprinidae).},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06588-7},
pmid = {41571710},
issn = {2052-4463},
abstract = {Opsariichthys evolans is a stream-dwelling fish species endemic to China, with its primary distribution encompassing southeastern China and Taiwan. Initially classified under the genus Zacco, it was later reclassified into the genus Opsariichthys based primarily on mitochondrial DNA evidence. However, this taxonomic revision remains partially inconclusive due to the absence of whole-genome data. Therefore, we assembled a telomere-to-telomere, gap-free genome assembly of O. evolans, consisting of 39 chromosomes with one contiguous sequence per chromosome. The assembly had a total size of 886.9 Mb and a contig N50 of 25.44 Mb. The presence of the telomere repeat was clearly confirmed in the genome. BUSCO assessment confirmed 99.34% genome completeness. Collinearity analysis revealed high synteny between O. evolans, O. bidens and Zacco platypus. Genomic comparisons revealed key candidate genes and related biological pathways potentially responsible for color patterning and hydrodynamic adaptation. The complete O. evolans genome provides insights into its genome structure and function, and supports the taxonomic reclassification between the genera Opsariichthys and Zacco.},
}
RevDate: 2026-01-22
Integrative transcriptomic profiling links telomere dysfunction to cGAS-STING activation in heart failure signatures in mice and humans.
Cardiovascular research pii:8438863 [Epub ahead of print].
AIMS: Cardiomyocyte telomere shortening is evident during heart failure pathogenesis. Conversely, mice with engineered telomerase deficiency develop myocardial dysfunction accompanied by p53 activation and mitochondrial repression. Yet, critical aspects remain to be established: whether cardiac dysfunction in mice lacking telomerase components arises from myocardial-intrinsic effects or systemic consequences of telomere shortening, which broader transcriptional programs follow cardiomyocyte telomere shortening, and what implications these carry for clinical heart failure.
METHODS AND RESULTS: As a prerequisite, we generated telomerase-deficient mice across successive generations and confirmed increasing cardiac dysfunction by comprehensive cardiovascular phenotyping and assessment of mitochondrial function in isolated cardiomyocytes.Transcriptional and regulator analysis confirmed the telomere-p53-mitochondria axis but extended beyond it, revealing additional involvement of neurohumoral activation, senescence, and inflammation, notably type I interferon signaling. To contextualize these findings, we compared this profile with hypertensive heart failure induced by neurohumoral dysregulation (angiotensin II infusion, nephrectomy, salt overload; ANS model) and established a transcriptional hierarchy. In mTRG5 mice, regulators of telomere dysfunction and p53 activation ranked highest by significance and centrality, supporting telomere shortening as the primary upstream driver. In contrast, ANS mice showed higher-ranking neurohumoral regulators, indicating these govern secondary pathways.To pursue the strong type 1 interferon profile, we utilized myocardial profiles of mice with a lack of three-prime exonuclease 1 (TREX1), an established activator of the cGAS-STING pathway. Matching the profiles, we could confirm pronounced activity of cGAS-STING in mTRG5- and to a lesser degree in ANS mice and thus provide first evidence for cGAS-STING-activation in telomere shortening and heart failure.
CONCLUSION: Finally, comparing the mTRG5 profile to curated datasets of human and murine dilated- and ischemic cardiomyopathy revealed a robust statistical overlap, proportional to the heart failure severity in mice and man, fostering the clinical relevance.
Additional Links: PMID-41571554
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@article {pmid41571554,
year = {2026},
author = {Brandt, M and Khraisat, S and Luo, Q and Mayerle, M and Raaz, U and Tsao, P and Münzel, T and Lurz, P and Wenzel, P and Blau, HM},
title = {Integrative transcriptomic profiling links telomere dysfunction to cGAS-STING activation in heart failure signatures in mice and humans.},
journal = {Cardiovascular research},
volume = {},
number = {},
pages = {},
doi = {10.1093/cvr/cvag013},
pmid = {41571554},
issn = {1755-3245},
abstract = {AIMS: Cardiomyocyte telomere shortening is evident during heart failure pathogenesis. Conversely, mice with engineered telomerase deficiency develop myocardial dysfunction accompanied by p53 activation and mitochondrial repression. Yet, critical aspects remain to be established: whether cardiac dysfunction in mice lacking telomerase components arises from myocardial-intrinsic effects or systemic consequences of telomere shortening, which broader transcriptional programs follow cardiomyocyte telomere shortening, and what implications these carry for clinical heart failure.
METHODS AND RESULTS: As a prerequisite, we generated telomerase-deficient mice across successive generations and confirmed increasing cardiac dysfunction by comprehensive cardiovascular phenotyping and assessment of mitochondrial function in isolated cardiomyocytes.Transcriptional and regulator analysis confirmed the telomere-p53-mitochondria axis but extended beyond it, revealing additional involvement of neurohumoral activation, senescence, and inflammation, notably type I interferon signaling. To contextualize these findings, we compared this profile with hypertensive heart failure induced by neurohumoral dysregulation (angiotensin II infusion, nephrectomy, salt overload; ANS model) and established a transcriptional hierarchy. In mTRG5 mice, regulators of telomere dysfunction and p53 activation ranked highest by significance and centrality, supporting telomere shortening as the primary upstream driver. In contrast, ANS mice showed higher-ranking neurohumoral regulators, indicating these govern secondary pathways.To pursue the strong type 1 interferon profile, we utilized myocardial profiles of mice with a lack of three-prime exonuclease 1 (TREX1), an established activator of the cGAS-STING pathway. Matching the profiles, we could confirm pronounced activity of cGAS-STING in mTRG5- and to a lesser degree in ANS mice and thus provide first evidence for cGAS-STING-activation in telomere shortening and heart failure.
CONCLUSION: Finally, comparing the mTRG5 profile to curated datasets of human and murine dilated- and ischemic cardiomyopathy revealed a robust statistical overlap, proportional to the heart failure severity in mice and man, fostering the clinical relevance.},
}
RevDate: 2026-01-22
CmpDate: 2026-01-22
Gender-based differences in telomere attrition and long-term respiratory dysfunction in COVID-19 ICU survivors one year post-infection: implications for aging-associated pulmonary decline.
Frontiers in immunology, 16:1681454.
INTRODUCTION: A significant proportion of COVID-19 Intensive Care Unit (ICU) survivors develop long-term respiratory complications, including pulmonary fibrosis. Telomere attrition, a marker of cellular senescence, has emerged as a potential biomarker for post-COVID-19 sequelae. This study investigated the association between peripheral blood relative telomere length (RTL) and long-term pulmonary outcomes in COVID-19 ICU survivors, with a specific focus on gender-specific differences.
METHODS: ICU-admitted COVID-19 patients were followed for at least one year post-discharge. RTL was quantified from peripheral blood using monochromatic multiplex quantitative PCR (MMqPCR) at hospital admission and one-year post-discharge. Primary outcomes were respiratory symptoms and diffuse parenchymal lung disease (DPLD), assessed via imaging. Data were analyzed using gender-stratified generalized linear models, adjusted for clinical covariates.
RESULTS: At one year, 43.8% of patients reported respiratory symptoms and 23.9% developed DPLD. A total of 73 ICU survivors were included, with 51 men and 22 women. At one year, 43.8% of patients reported respiratory symptoms and 23.9% developed DPLD. Longitudinal analysis showed significant RTL shortening in both men and women who underwent IMV (p=0.011 and p=0.016, respectively), and in men who needed pronation during their ICU stay (p=0.037). Regarding one-year symptoms, in women, repeated-measures analysis showed an association with persistent respiratory symptoms, particularly in those who needed pronation during their ICU stay [adjusted arithmetic mean ratio (aAMR)=0.73) (95%CI=0.60-0.90); p=0.003]. At follow-up, women who had undergone pronation and had shorter RTL continued to show a higher prevalence of symptoms [aAMR= 0.66 (0.58-0.76); p< 0.001]. In contrast, men with shorter RTL at one-year post-discharge had an association with the presence of DPLD [aAMR = 0.64 (0.50-0.81); p = 0.001]. This association in men was significant particularly among those who required IMV [aAMR= 0.61 (0.49-0.76); p< 0.001] or prone positioning [aAMR= 0.56 (0.44-0.71); p= 0.016].
DISCUSSION: These findings underscore the role of telomere attrition as a sex-specific biomarker of aging-associated pulmonary vulnerability in the aftermath of critical COVID-19 illness. RTL may serve as a prognostic marker for long-term respiratory sequelae, potentially guiding risk stratification and individualized follow-up strategies in post-ICU COVID-19 survivors.
Additional Links: PMID-41567226
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@article {pmid41567226,
year = {2025},
author = {Behar-Lagares, R and Virseda-Berdices, A and Martínez-González, Ó and Blancas, R and Manteiga, E and Muñoz-García, P and Mallol Poyato, MJ and Molina Del Pozo, J and Homez-Guzmán, M and Alonso Fernández, MA and Resino, S and Fernández-Rodríguez, A and Jiménez-Sousa, MÁ},
title = {Gender-based differences in telomere attrition and long-term respiratory dysfunction in COVID-19 ICU survivors one year post-infection: implications for aging-associated pulmonary decline.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1681454},
pmid = {41567226},
issn = {1664-3224},
mesh = {Humans ; Female ; Male ; *COVID-19/complications ; Middle Aged ; Aged ; Survivors ; Intensive Care Units ; *SARS-CoV-2 ; Sex Factors ; *Telomere ; *Telomere Shortening ; *Aging ; },
abstract = {INTRODUCTION: A significant proportion of COVID-19 Intensive Care Unit (ICU) survivors develop long-term respiratory complications, including pulmonary fibrosis. Telomere attrition, a marker of cellular senescence, has emerged as a potential biomarker for post-COVID-19 sequelae. This study investigated the association between peripheral blood relative telomere length (RTL) and long-term pulmonary outcomes in COVID-19 ICU survivors, with a specific focus on gender-specific differences.
METHODS: ICU-admitted COVID-19 patients were followed for at least one year post-discharge. RTL was quantified from peripheral blood using monochromatic multiplex quantitative PCR (MMqPCR) at hospital admission and one-year post-discharge. Primary outcomes were respiratory symptoms and diffuse parenchymal lung disease (DPLD), assessed via imaging. Data were analyzed using gender-stratified generalized linear models, adjusted for clinical covariates.
RESULTS: At one year, 43.8% of patients reported respiratory symptoms and 23.9% developed DPLD. A total of 73 ICU survivors were included, with 51 men and 22 women. At one year, 43.8% of patients reported respiratory symptoms and 23.9% developed DPLD. Longitudinal analysis showed significant RTL shortening in both men and women who underwent IMV (p=0.011 and p=0.016, respectively), and in men who needed pronation during their ICU stay (p=0.037). Regarding one-year symptoms, in women, repeated-measures analysis showed an association with persistent respiratory symptoms, particularly in those who needed pronation during their ICU stay [adjusted arithmetic mean ratio (aAMR)=0.73) (95%CI=0.60-0.90); p=0.003]. At follow-up, women who had undergone pronation and had shorter RTL continued to show a higher prevalence of symptoms [aAMR= 0.66 (0.58-0.76); p< 0.001]. In contrast, men with shorter RTL at one-year post-discharge had an association with the presence of DPLD [aAMR = 0.64 (0.50-0.81); p = 0.001]. This association in men was significant particularly among those who required IMV [aAMR= 0.61 (0.49-0.76); p< 0.001] or prone positioning [aAMR= 0.56 (0.44-0.71); p= 0.016].
DISCUSSION: These findings underscore the role of telomere attrition as a sex-specific biomarker of aging-associated pulmonary vulnerability in the aftermath of critical COVID-19 illness. RTL may serve as a prognostic marker for long-term respiratory sequelae, potentially guiding risk stratification and individualized follow-up strategies in post-ICU COVID-19 survivors.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
Female
Male
*COVID-19/complications
Middle Aged
Aged
Survivors
Intensive Care Units
*SARS-CoV-2
Sex Factors
*Telomere
*Telomere Shortening
*Aging
RevDate: 2026-01-21
Leukocyte telomere attrition following radiotherapy in prostate cancer: a prospective study.
Scientific reports pii:10.1038/s41598-026-36205-x [Epub ahead of print].
Telomeres are protective protein-bound DNA repeat structures at the end of chromosomes, which play a critical role in maintaining chromosomal stability. With each somatic-cell division, telomeres progressively shorten, making telomere length a potential biomarker of biological aging. Ionizing radiation may accelerate telomere attrition, thereby promoting aging-related changes. In the present study, we analyzed the influence of radiotherapy on leucocyte telomere length in prostate cancer patients. A total of 314 patients treated with curative radiotherapy for prostate cancer were included in the present prospective study. Leukocyte relative telomere length (RTL) was measured by qPCR in peripheral blood samples collected before radiotherapy, at the end of radiotherapy, and at 3 and 15 months post-radiotherapy. Mean RTL values were 0.65 ± 0.34 at baseline, 0.62 ± 0.31 at the end of radiotherapy, 0.67 ± 0.43, and 0.55 ± 0.26 at the first and at the second follow-up, respectively. . Paired-Samples T-Test comparisons showed a significant reduction in RTL at 15 months post- radiotherapy compared to baseline (p < 0.001), end of radiotherapy (p = 0.001), and 3-month follow-up examination (p < 0.001). In our cohort, we observed a significant shortening of telomeres after radiotherapy indicating a potential contribution to accelerated cellular aging.
Additional Links: PMID-41565875
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PubMed:
Citation:
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@article {pmid41565875,
year = {2026},
author = {Langsenlehner, T and Paal, K and Thurner, EM and Genser, S and Sternat, R and Stranz, B and Renner, W},
title = {Leukocyte telomere attrition following radiotherapy in prostate cancer: a prospective study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36205-x},
pmid = {41565875},
issn = {2045-2322},
abstract = {Telomeres are protective protein-bound DNA repeat structures at the end of chromosomes, which play a critical role in maintaining chromosomal stability. With each somatic-cell division, telomeres progressively shorten, making telomere length a potential biomarker of biological aging. Ionizing radiation may accelerate telomere attrition, thereby promoting aging-related changes. In the present study, we analyzed the influence of radiotherapy on leucocyte telomere length in prostate cancer patients. A total of 314 patients treated with curative radiotherapy for prostate cancer were included in the present prospective study. Leukocyte relative telomere length (RTL) was measured by qPCR in peripheral blood samples collected before radiotherapy, at the end of radiotherapy, and at 3 and 15 months post-radiotherapy. Mean RTL values were 0.65 ± 0.34 at baseline, 0.62 ± 0.31 at the end of radiotherapy, 0.67 ± 0.43, and 0.55 ± 0.26 at the first and at the second follow-up, respectively. . Paired-Samples T-Test comparisons showed a significant reduction in RTL at 15 months post- radiotherapy compared to baseline (p < 0.001), end of radiotherapy (p = 0.001), and 3-month follow-up examination (p < 0.001). In our cohort, we observed a significant shortening of telomeres after radiotherapy indicating a potential contribution to accelerated cellular aging.},
}
RevDate: 2026-01-21
Title: Mitochondrial Integrity, Telomere Dynamics, and Causal Pathways in Pulmonary Fibrosis: Reappraisal of a Mendelian Analysis.
QJM : monthly journal of the Association of Physicians pii:8435839 [Epub ahead of print].
Additional Links: PMID-41565372
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PubMed:
Citation:
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@article {pmid41565372,
year = {2026},
author = {Ting, TL and Lee, YT},
title = {Title: Mitochondrial Integrity, Telomere Dynamics, and Causal Pathways in Pulmonary Fibrosis: Reappraisal of a Mendelian Analysis.},
journal = {QJM : monthly journal of the Association of Physicians},
volume = {},
number = {},
pages = {},
doi = {10.1093/qjmed/hcag023},
pmid = {41565372},
issn = {1460-2393},
}
RevDate: 2026-01-21
Reply: Comment on "New insights from mendelian randomization and mediation analysis: causal relationships between mitochondrial DNA copy number and telomere length in pulmonary fibrosis".
QJM : monthly journal of the Association of Physicians pii:8435838 [Epub ahead of print].
Additional Links: PMID-41565371
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PubMed:
Citation:
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@article {pmid41565371,
year = {2026},
author = {Li, Y and Hou, L},
title = {Reply: Comment on "New insights from mendelian randomization and mediation analysis: causal relationships between mitochondrial DNA copy number and telomere length in pulmonary fibrosis".},
journal = {QJM : monthly journal of the Association of Physicians},
volume = {},
number = {},
pages = {},
doi = {10.1093/qjmed/hcag025},
pmid = {41565371},
issn = {1460-2393},
}
RevDate: 2026-01-21
Correction: Pan-cancer analysis of telomere maintenance mechanisms.
Additional Links: PMID-41564788
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PubMed:
Citation:
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@article {pmid41564788,
year = {2026},
author = {Hakobyan, M and Binder, H and Arakelyan, A},
title = {Correction: Pan-cancer analysis of telomere maintenance mechanisms.},
journal = {The Journal of biological chemistry},
volume = {302},
number = {2},
pages = {111130},
doi = {10.1016/j.jbc.2025.111130},
pmid = {41564788},
issn = {1083-351X},
}
RevDate: 2026-01-21
Lymphoid malignancy and clonality in the POT1-mediated long telomere syndrome.
Blood pii:566170 [Epub ahead of print].
Long telomere length (TL) extends replicative capacity in vitro, and predisposes to clonal hematopoiesis. We characterized the cancer phenotype in 51 individuals from 24 families with mutant POT1, a negative regulator of telomerase elongation (median age 51, range 5-94). Hematologic malignancies were second in prevalence after melanoma (27%), and lymphoid subsets were more common. They clustered with history of sarcoma, thyroid cancer and chronic myeloproliferative neoplasms. UKB participants with pathogenic POT1 variants had long TL and higher lymphoid malignancy rates (45% by age 80, Hazard ratio 8.28, 95% CI, 5.29-13.0). Across cohorts, diagnoses encompassed acute lymphoblastic leukemia and Hodgkin lymphoma in children/young adults, and chronic lymphocytic leukemia/multiple myeloma in adults. They clustered in families manifesting as autosomal dominant pan-lymphoma with genetic anticipation at times. Lymphocyte TL was longer than granulocytes at baseline (age-adjusted mean +1 kb, P<0.0001), and was preserved longitudinally with aging. Ultra-long lymphocyte TL >99th percentile was more sensitive for identifying pathogenic variants (58% vs. 38% for granulocytes). Among asymptomatic POT1 variant carriers, 60% (12 of 20) had immunophenotype-detected B and/or T cell clonality with complete penetrance after age 65 (7 of 7). IGH CDR3 sequencing supported age-dependent pruning of the B cell repertoire, and cytogenetic and next-generation analyses uncovered preclinical clonal lymphoma-associated changes in nearly all POT1 variant carriers older than 60 (9 of 10). Our data identify extended cellular longevity due to long TL as an inherited risk factor for lymphoma explaining its syndromic association with solid tumors, and in some cases, myeloproliferative neoplasms.
Additional Links: PMID-41564438
Publisher:
PubMed:
Citation:
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@article {pmid41564438,
year = {2026},
author = {Davidson-Swinton, HR and Iyer, S and Kolchinski, A and Salem, JA and DeBoy, EA and Kilada, AG and Hwang, JS and Jain, T and Keel, SB and Gocke, CD and Zou, YS and Schratz, KE and Armanios, M},
title = {Lymphoid malignancy and clonality in the POT1-mediated long telomere syndrome.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031287},
pmid = {41564438},
issn = {1528-0020},
abstract = {Long telomere length (TL) extends replicative capacity in vitro, and predisposes to clonal hematopoiesis. We characterized the cancer phenotype in 51 individuals from 24 families with mutant POT1, a negative regulator of telomerase elongation (median age 51, range 5-94). Hematologic malignancies were second in prevalence after melanoma (27%), and lymphoid subsets were more common. They clustered with history of sarcoma, thyroid cancer and chronic myeloproliferative neoplasms. UKB participants with pathogenic POT1 variants had long TL and higher lymphoid malignancy rates (45% by age 80, Hazard ratio 8.28, 95% CI, 5.29-13.0). Across cohorts, diagnoses encompassed acute lymphoblastic leukemia and Hodgkin lymphoma in children/young adults, and chronic lymphocytic leukemia/multiple myeloma in adults. They clustered in families manifesting as autosomal dominant pan-lymphoma with genetic anticipation at times. Lymphocyte TL was longer than granulocytes at baseline (age-adjusted mean +1 kb, P<0.0001), and was preserved longitudinally with aging. Ultra-long lymphocyte TL >99th percentile was more sensitive for identifying pathogenic variants (58% vs. 38% for granulocytes). Among asymptomatic POT1 variant carriers, 60% (12 of 20) had immunophenotype-detected B and/or T cell clonality with complete penetrance after age 65 (7 of 7). IGH CDR3 sequencing supported age-dependent pruning of the B cell repertoire, and cytogenetic and next-generation analyses uncovered preclinical clonal lymphoma-associated changes in nearly all POT1 variant carriers older than 60 (9 of 10). Our data identify extended cellular longevity due to long TL as an inherited risk factor for lymphoma explaining its syndromic association with solid tumors, and in some cases, myeloproliferative neoplasms.},
}
RevDate: 2026-01-21
Exploring the impact of the common (4977 bp) and ATPase mitochondrial DNA deletion on the copy number and telomere length in a sample of infertile Iraqi men.
Molecular biology reports, 53(1):312.
Additional Links: PMID-41563601
PubMed:
Citation:
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@article {pmid41563601,
year = {2026},
author = {Aboalselan, MFK and Mohammed, MQ and Samawi, FT and Gargouri, A},
title = {Exploring the impact of the common (4977 bp) and ATPase mitochondrial DNA deletion on the copy number and telomere length in a sample of infertile Iraqi men.},
journal = {Molecular biology reports},
volume = {53},
number = {1},
pages = {312},
pmid = {41563601},
issn = {1573-4978},
}
RevDate: 2026-01-21
Haplotype-resolved telomere-to-telomere genome of the jade vine (Strongylodon macrobotrys) provides novel insights into the turquoise flower coloration.
Journal of integrative plant biology [Epub ahead of print].
A haplotype-resolved telomere-to-telomere genome reveals that the bird-shaped turquoise flowers of Strongylodon macrobotrys (jade vine) arise from co-pigmentation between the anthocyanin malvin and the flavonoid saponarin, shaped by genome dynamics and geological event-associated expansions of long terminal repeat retrotransposons.
Additional Links: PMID-41560423
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PubMed:
Citation:
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@article {pmid41560423,
year = {2026},
author = {Liu, TJ and Wang, XF and Shi, DD and Wang, ZQ and Bi, GQ and Lin, ZL and Huang, HR and Ge, XJ and Li, LF and Yan, HF and Zeng, SH and Ning, ZL},
title = {Haplotype-resolved telomere-to-telomere genome of the jade vine (Strongylodon macrobotrys) provides novel insights into the turquoise flower coloration.},
journal = {Journal of integrative plant biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jipb.70136},
pmid = {41560423},
issn = {1744-7909},
support = {2022B111123000//Guangdong Science and Technology Program/ ; 2023B1212060046//Guangdong Science and Technology Program/ ; },
abstract = {A haplotype-resolved telomere-to-telomere genome reveals that the bird-shaped turquoise flowers of Strongylodon macrobotrys (jade vine) arise from co-pigmentation between the anthocyanin malvin and the flavonoid saponarin, shaped by genome dynamics and geological event-associated expansions of long terminal repeat retrotransposons.},
}
RevDate: 2026-01-20
A telomere-based prognostic model incorporating E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1 for hepatocellular carcinoma.
European journal of medical research pii:10.1186/s40001-026-03900-4 [Epub ahead of print].
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy associated with an unfavorable prognosis. Telomeres and telomere-related genes are central to tumorigenesis, but their systematic integration into prognostic modeling for HCC remains insufficiently explored. This study presents a telomere-based prognostic model aimed at improving risk stratification and informing therapeutic decision-making in HCC.
METHODS: Transcriptomic profiles and clinical data were collected from The Cancer Genome Atlas (369 HCC and 50 normal samples) and Hepatocellular Carcinoma Gene Expression Database (203 cases). A curated panel of 2,093 telomere-related genes was retrieved from TelNet. Hub genes were identified using an integrated strategy combining ssGSEA, WGCNA, and differential expression analysis. A prognostic risk model was established using univariate Cox, LASSO, and multivariate Cox regression analyses, followed by external validation.
RESULTS: We developed a robust telomere-based prognostic model featuring six key genes: E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1. This six-gene signature stratified patients with HCC into high- and low-risk subgroups with significantly different overall survival (P < 0.05) across training and validation cohorts. Multivariate analyses confirmed the risk score as an independent prognostic factor. Functional analysis revealed significant enrichment of DNA replication and cell cycle pathways in high-risk patients. Immune profiling showed distinct infiltration patterns and elevated immune evasion potential in the high-risk group. Drug sensitivity analyses highlighted potential therapeutic vulnerabilities to specific inhibitors.
CONCLUSION: This study established a telomere-based prognostic model for HCC. This model provides reliable survival prediction, captures key tumor microenvironment features, and yields insights to support personalized therapeutic strategies, offering a valuable tool for clinical decision-making in HCC.
Additional Links: PMID-41559780
Publisher:
PubMed:
Citation:
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@article {pmid41559780,
year = {2026},
author = {Wang, Y and Fu, L and Yang, Z and Wang, W and Sun, J and Gu, X},
title = {A telomere-based prognostic model incorporating E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1 for hepatocellular carcinoma.},
journal = {European journal of medical research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40001-026-03900-4},
pmid = {41559780},
issn = {2047-783X},
support = {2024HLTJ15//The Third HeLuo Youth Talent Support Project/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy associated with an unfavorable prognosis. Telomeres and telomere-related genes are central to tumorigenesis, but their systematic integration into prognostic modeling for HCC remains insufficiently explored. This study presents a telomere-based prognostic model aimed at improving risk stratification and informing therapeutic decision-making in HCC.
METHODS: Transcriptomic profiles and clinical data were collected from The Cancer Genome Atlas (369 HCC and 50 normal samples) and Hepatocellular Carcinoma Gene Expression Database (203 cases). A curated panel of 2,093 telomere-related genes was retrieved from TelNet. Hub genes were identified using an integrated strategy combining ssGSEA, WGCNA, and differential expression analysis. A prognostic risk model was established using univariate Cox, LASSO, and multivariate Cox regression analyses, followed by external validation.
RESULTS: We developed a robust telomere-based prognostic model featuring six key genes: E2F1, MYCN, VPS72, CFAP53, OR8A1, and TXNRD1. This six-gene signature stratified patients with HCC into high- and low-risk subgroups with significantly different overall survival (P < 0.05) across training and validation cohorts. Multivariate analyses confirmed the risk score as an independent prognostic factor. Functional analysis revealed significant enrichment of DNA replication and cell cycle pathways in high-risk patients. Immune profiling showed distinct infiltration patterns and elevated immune evasion potential in the high-risk group. Drug sensitivity analyses highlighted potential therapeutic vulnerabilities to specific inhibitors.
CONCLUSION: This study established a telomere-based prognostic model for HCC. This model provides reliable survival prediction, captures key tumor microenvironment features, and yields insights to support personalized therapeutic strategies, offering a valuable tool for clinical decision-making in HCC.},
}
RevDate: 2026-01-20
The Ess1 prolyl isomerase represses TERRA transcription and promotes telomere replication in Saccharomyces cerevisiae.
Genetics pii:8431689 [Epub ahead of print].
The conserved Ess1 prolyl isomerase (PIN1 in human) binds the carboxy-terminal domain (CTD) of RNA Pol II, and plays multiple roles in transcription regulation. Consistent with an essential role of the human PIN1 in telomere maintenance, previous screenings have identified the yeast Ess1 as a telomere length maintenance gene. Here, we provide evidence that Ess1 is involved in regulating both telomere transcription and replication. We find that depletion of Ess1 leads to a failure in transcription termination, explaining the essential role of Ess1 in maintaining a low level of telomere repeat containing RNA (TERRA). Furthermore, we show that Ess1 depletion promotes telomere shortening and accelerates senescence in telomerase-deficient cells. Notably, the depletion of Ess1 causes synthetic growth defects and telomere shortening in mre11Δ cells, and compromises rif2Δ-induced telomere elongation. Additionally, Ess1 depletion also accelerates senescence and eliminates type II telomere recombination in rad50Δ tlc1Δ cells. Lastly, Ess1 depletion decreases the accumulation of single-stranded DNA at telomere ends. These results support the model that Ess1 positively regulates both telomerase- and recombination-dependent telomere replication by promoting telomere-end resection. Taken together, this study reveals the yeast Ess1 as a new regulator of telomere transcription and replication via a distinct mechanism from the human PIN1.
Additional Links: PMID-41557636
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PubMed:
Citation:
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@article {pmid41557636,
year = {2026},
author = {Chen, J and Yang, L and Zhu, X and Wu, J and Lei, M and Wu, Z},
title = {The Ess1 prolyl isomerase represses TERRA transcription and promotes telomere replication in Saccharomyces cerevisiae.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyag017},
pmid = {41557636},
issn = {1943-2631},
abstract = {The conserved Ess1 prolyl isomerase (PIN1 in human) binds the carboxy-terminal domain (CTD) of RNA Pol II, and plays multiple roles in transcription regulation. Consistent with an essential role of the human PIN1 in telomere maintenance, previous screenings have identified the yeast Ess1 as a telomere length maintenance gene. Here, we provide evidence that Ess1 is involved in regulating both telomere transcription and replication. We find that depletion of Ess1 leads to a failure in transcription termination, explaining the essential role of Ess1 in maintaining a low level of telomere repeat containing RNA (TERRA). Furthermore, we show that Ess1 depletion promotes telomere shortening and accelerates senescence in telomerase-deficient cells. Notably, the depletion of Ess1 causes synthetic growth defects and telomere shortening in mre11Δ cells, and compromises rif2Δ-induced telomere elongation. Additionally, Ess1 depletion also accelerates senescence and eliminates type II telomere recombination in rad50Δ tlc1Δ cells. Lastly, Ess1 depletion decreases the accumulation of single-stranded DNA at telomere ends. These results support the model that Ess1 positively regulates both telomerase- and recombination-dependent telomere replication by promoting telomere-end resection. Taken together, this study reveals the yeast Ess1 as a new regulator of telomere transcription and replication via a distinct mechanism from the human PIN1.},
}
RevDate: 2026-01-20
Phytogenic effects of Brachiaria decumbens saponin extract on growth performance, immune response, and telomere dynamics in broiler chickens under tropical conditions.
Tropical animal health and production, 58(2):58.
Additional Links: PMID-41557061
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@article {pmid41557061,
year = {2026},
author = {Chung, ELT and Kassim, NA and Zheng, ALT and Jesse, FFA and Loh, TC and Dunshea, FR},
title = {Phytogenic effects of Brachiaria decumbens saponin extract on growth performance, immune response, and telomere dynamics in broiler chickens under tropical conditions.},
journal = {Tropical animal health and production},
volume = {58},
number = {2},
pages = {58},
pmid = {41557061},
issn = {1573-7438},
support = {07-01-20-2256FR//Kementerian Sains, Teknologi dan Inovasi/ ; },
}
RevDate: 2026-01-20
CmpDate: 2026-01-20
Parental Age Effects on Offspring Telomere Length Across Vertebrates: A Meta-Analysis.
Molecular ecology, 35(2):e70215.
Telomeres shorten with advancing age in numerous species, and shorter telomeres are linked to increased mortality risk. While parental age at conception can influence offspring telomere length, the magnitude and direction of this effect differ across studies, species, and parental sexes. To understand how parental age influences offspring telomere length across vertebrates, we conducted a systematic review and meta-analysis to examine the effects of paternal and maternal age at conception on offspring telomere length, incorporating 99 effect sizes from 30 human studies and 49 effect sizes from 12 non-human vertebrate studies. There was a positive overall parental age effect on offspring telomere length within human studies, while no effect was found in non-human vertebrate studies after adjusting for study, estimate, and phylogenetic effects. Considerable heterogeneity was attributed mainly to between-study variance in human studies and to phylogeny in non-human studies. Parental age effect estimates were correlated with the laboratory methods used for measuring telomere length in all studies. In human studies, the interaction between parental and offspring sex affected the parental age effect estimates, and estimates derived from leukocytes were less positive than those from other cells. In non-human vertebrates, parental age effects were less negative when the parents' identity was controlled for in the study. Publication biases suggest overestimation of the parental age effect in human studies. We recommend that future research be conducted on a broader range of taxa, test for within-parent effects, and follow standardised reporting practices to enhance data comparability.
Additional Links: PMID-41556533
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PubMed:
Citation:
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@article {pmid41556533,
year = {2026},
author = {Vlasova, M and Sun, Y and Chik, HYJ and Dugdale, HL},
title = {Parental Age Effects on Offspring Telomere Length Across Vertebrates: A Meta-Analysis.},
journal = {Molecular ecology},
volume = {35},
number = {2},
pages = {e70215},
doi = {10.1111/mec.70215},
pmid = {41556533},
issn = {1365-294X},
support = {//Rijksuniversiteit Groningen/ ; //Rosalind Franklin Fellowship, University of Groninben/ ; },
mesh = {Humans ; Animals ; *Telomere/genetics ; *Vertebrates/genetics ; Female ; Male ; *Paternal Age ; *Maternal Age ; Phylogeny ; *Telomere Homeostasis ; },
abstract = {Telomeres shorten with advancing age in numerous species, and shorter telomeres are linked to increased mortality risk. While parental age at conception can influence offspring telomere length, the magnitude and direction of this effect differ across studies, species, and parental sexes. To understand how parental age influences offspring telomere length across vertebrates, we conducted a systematic review and meta-analysis to examine the effects of paternal and maternal age at conception on offspring telomere length, incorporating 99 effect sizes from 30 human studies and 49 effect sizes from 12 non-human vertebrate studies. There was a positive overall parental age effect on offspring telomere length within human studies, while no effect was found in non-human vertebrate studies after adjusting for study, estimate, and phylogenetic effects. Considerable heterogeneity was attributed mainly to between-study variance in human studies and to phylogeny in non-human studies. Parental age effect estimates were correlated with the laboratory methods used for measuring telomere length in all studies. In human studies, the interaction between parental and offspring sex affected the parental age effect estimates, and estimates derived from leukocytes were less positive than those from other cells. In non-human vertebrates, parental age effects were less negative when the parents' identity was controlled for in the study. Publication biases suggest overestimation of the parental age effect in human studies. We recommend that future research be conducted on a broader range of taxa, test for within-parent effects, and follow standardised reporting practices to enhance data comparability.},
}
MeSH Terms:
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Humans
Animals
*Telomere/genetics
*Vertebrates/genetics
Female
Male
*Paternal Age
*Maternal Age
Phylogeny
*Telomere Homeostasis
RevDate: 2026-01-20
Cancer risk in patients with pulmonary fibrosis and a rare telomere related gene variant.
Respiratory research pii:10.1186/s12931-025-03469-2 [Epub ahead of print].
Additional Links: PMID-41555406
Publisher:
PubMed:
Citation:
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@article {pmid41555406,
year = {2026},
author = {van der Vis, JJ and Maus, MTK and de Bie, CI and van der Smagt, JJ and Daenen, LGM and van Oosterhout, MFM and Grutters, JC and van Moorsel, CHM},
title = {Cancer risk in patients with pulmonary fibrosis and a rare telomere related gene variant.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-025-03469-2},
pmid = {41555406},
issn = {1465-993X},
support = {TZO: 10070012010004/ZONMW_/ZonMw/Netherlands ; TZO: 10070012010004/ZONMW_/ZonMw/Netherlands ; TZO: 10070012010004/ZONMW_/ZonMw/Netherlands ; },
}
RevDate: 2026-01-18
miR-155-SOCS1-Telomere Length Axis: A Tripartite and Multifaceted Approach To Understanding Rheumatoid Arthritis Pathophysiology.
Cell biochemistry and biophysics [Epub ahead of print].
Additional Links: PMID-41549164
PubMed:
Citation:
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@article {pmid41549164,
year = {2026},
author = {Tariq, S and Ejaz, S and Liaqat, A and Sarwar, S and Hussain, F and Begum, M and Zafar, F and Hussain, Z and Zia, S},
title = {miR-155-SOCS1-Telomere Length Axis: A Tripartite and Multifaceted Approach To Understanding Rheumatoid Arthritis Pathophysiology.},
journal = {Cell biochemistry and biophysics},
volume = {},
number = {},
pages = {},
pmid = {41549164},
issn = {1559-0283},
}
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RJR Experience and Expertise
Researcher
Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.
Educator
Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.
Administrator
Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.
Technologist
Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.
Publisher
While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.
Speaker
Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.
Facilitator
Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.
Designer
Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.
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Big Data & Informatics
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