@article {pmid40169648,
year = {2025},
author = {Yue, X and Liu, H and Guo, W and Gao, Y and Shi, S},
title = {Causal association between dietary factors and telomere length revealed by mendelian randomization.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {11082},
pmid = {40169648},
issn = {2045-2322},
support = {YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *Diet ; *Telomere/genetics ; *Genome-Wide Association Study ; *Telomere Homeostasis ; Polymorphism, Single Nucleotide ; Fruit/genetics ; },
abstract = {Observational studies have reported associations between dietary factors and telomere length. However, the inherent limitations of observational study designs render them susceptible to confounding and reverse causation biases. Therefore, this study aims to explore the association between dietary factors and telomere length using Mendelian Randomization (MR) to minimize the influence of confounding factors and reverse causality. The IEU Open GWAS project was the source of exposure and outcome datasets. The exposure datasets included 20 dietary factors. We conducted MR analyses to explore the relationship between dietary factors and telomere length. We used MRPRESSO and Radial-MR test to identify any level of multi-effect outliers. Heterogeneity and pleiotropic analysis were performed to ensure the accuracy of the results. The stability of the effect of significant results is assessed using multivariable Mendelian randomization (MVMR) and MR-lap. Two-sample MR analysis revealed a statistically significant association between dried fruit intake and telomere length (β = 0.223, 95% CI 0.091 to 0.356, PIVW=9.089 × 10^-4). After removing outliers and reanalyzing the data, the association remained significant (β = 0.163, 95% CI: 0.163 0.090 to 0.235, PIVW-FE=7.323 × 10^-5), with no significant pleiotropy detected in sensitivity analyses. Following adjustment for confounders, the MVMR results and MR-lap results continued to support a causal relationship between dried fruit intake and telomere length. Other dietary factors' effects on telomere length still need further confirmation. Our findings suggest a potential causal relationship between dried fruit intake and longer telomere length. This finding highlights potential dietary strategies for exploring the beneficial effects of dried fruit intake on preventing diseases and extending lifespan.},
}

*Mendelian Randomization Analysis
Humans
*Diet
*Telomere/genetics
*Genome-Wide Association Study
*Telomere Homeostasis
Polymorphism, Single Nucleotide
Fruit/genetics

@article {pmid40169380,
year = {2025},
author = {Chung, G and Piano, F and Gunsalus, KC},
title = {TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkaf062},
pmid = {40169380},
issn = {2160-1836},
abstract = {Telomeres are eukaryotic chromosome end structures that guard against sequence loss and aberrant chromosome fusions. Telomeric repeat motifs (TRMs), the minimal repeating unit of a telomere, vary from species to species, with some evolutionary clades experiencing a rapid sequence divergence. To explore the full scope of this evolutionary divergence, many bioinformatic tools have been developed to infer novel TRMs using repetitive sequence search on short sequencing reads. However, novel telomeric motifs remain unidentified in up to half of the sequencing libraries assayed with these tools. A possible reason may be that short reads, derived from extensively sheared DNA, preserve little to no positional context of the repetitive sequences assayed. On the other hand, if a sequencing read is sufficiently long, telomeric sequences must appear at either end rather than in the middle. The TeloSearchLR algorithm relies on this to help identify novel TRMs on long reads, in many cases where short-read search tools have failed. In addition, we demonstrate that TeloSearchLR can reveal unusually long telomeric motifs not maintained by telomerase, and it can also be used to anchor terminal scaffolds in new genome assemblies.},
}

@article {pmid40167991,
year = {2025},
author = {Qi, Z and Liu, Q and Li, H and Zhang, Y and Yu, Z and Luo, W and Wang, K and Zhang, Y and Pan, S and Wang, C and Jiang, H and Qiu, Q and Wang, W and Fan, G and Li, Y},
title = {Telomere-to-telomere genome assembly of Electrophorus electricus provides insights into the evolution of electric eels.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf024},
pmid = {40167991},
issn = {2047-217X},
support = {31900312//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Electrophorus/genetics ; *Telomere/genetics ; *Genome ; Evolution, Molecular ; Molecular Sequence Annotation ; Phylogeny ; Genomics/methods ; },
abstract = {BACKGROUND: Electric eels evolved remarkable electric organs that enable them to instantaneously discharge hundreds of volts for predation, defense, and communication. However, the absence of a high-quality reference genome has extremely constrained the studies of electric eels in various aspects.

RESULTS: Using high-depth, multiplatform sequencing data, we successfully assembled the first telomere-to-telomere high-quality reference genome of Electrophorus electricus, which has a genome size of 833.43 Mb and comprises 26 chromosomes. Multiple evaluations, including N50 statistics (30.38 Mb), BUSCO scores (97.30%), and mapping ratio of short-insert sequencing data (99.91%), demonstrate the high contiguity and completeness of the electric eel genome assembly we obtained. Genome annotation predicted 396.63 Mb repetitive sequences and 20,992 protein-coding genes. Furthermore, evolutionary analyses indicate that Gymnotiformes, which the electric eel belongs to, has a closer relationship with Characiformes than Siluriformes and diverged from Characiformes 95.00 million years ago. Pairwise sequentially Markovian coalescent analysis found a sharply decreased trend of the population size of E. electricus over the past few hundred thousand years. Furthermore, many regulatory factors related to neurotransmitters and classical signaling pathways during embryonic development were significantly expanded, potentially contributing to the generation of high-voltage electricity.

CONCLUSIONS: This study not only provided the first high-quality telomere-to-telomere reference genome of E. electricus but also greatly enhanced our understanding of electric eels.},
}

Animals
*Electrophorus/genetics
*Telomere/genetics
*Genome
Evolution, Molecular
Molecular Sequence Annotation
Phylogeny
Genomics/methods

@article {pmid40164629,
year = {2025},
author = {Dong, Z and Gao, J and Zhao, Y and Gao, J and Guo, Y and Wang, Z and Zhang, N},
title = {Near telomere-to-telomere genome assembly of the blackspot tuskfish (Choerodon schoenleinii).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {537},
pmid = {40164629},
issn = {2052-4463},
mesh = {*Genome ; *Telomere/genetics ; Animals ; Molecular Sequence Annotation ; Tetraodontiformes/genetics ; },
abstract = {Choerodon schoenleinii, commonly known as the blackspot tuskfish, widely recognized for its vibrant coloration, unique small black spot on the dorsal fin, and high value in both ornamental and culinary markets. Here, we report a high-quality near telomere-to-telomere (T2T) genome assembly of C. schoenleinii, generated using PacBio HiFi and Hi-C technologies. The assembly spans 865.99 Mb, achieving chromosome-level resolution with 24 chromosomes anchored. Notably, telomeres were identified at both ends of 23 chromosomes, with 14 being completely gapless and only 12 gaps detected across the remaining nine. A total of 24,524 protein-coding genes were annotated, with 96.25% assigned functional annotations. The assembly quality was validated with a BUSCO score of 99.80%. The gene annotation was further evaluated using OMArk, with 23,590 proteins (96.19%) consistent with the Clade Teleostei, highlighting the high-quality and taxonomic relevance of the gene set. This reference genome provides a valuable resource for advancing research in the genetics, evolutionary biology, conservation, and breeding of C. schoenleinii, a species currently listed as "Near Threatened" by the IUCN.},
}

*Genome
*Telomere/genetics
Animals
Molecular Sequence Annotation
Tetraodontiformes/genetics

@article {pmid40159528,
year = {2025},
author = {Liu, Z and Sun, C and Zhang, Z and Jiang, Y and Zhao, C},
title = {Telomeres in skin aging.},
journal = {Biogerontology},
volume = {26},
number = {2},
pages = {83},
pmid = {40159528},
issn = {1573-6768},
mesh = {*Skin Aging/physiology/genetics ; Humans ; *Telomere/metabolism ; Skin/metabolism ; Telomerase/metabolism ; Telomere Homeostasis/physiology ; Animals ; Telomere Shortening ; },
abstract = {Skin aging is influenced by both intrinsic and extrinsic factors. The gradual manifestation of changes in telomere length and telomerase activity, as crucial indicators of aging, elucidates the underlying mechanism of skin aging. This review aims to comprehensively analyze the association between telomeres and aging, along with their impact on skin biological function. Firstly, we summarize the structure and function of telomeres and their role in cell division. Subsequently, we discuss the mechanisms through which telomere regulation contributes to aging processes while analyzing its involvement in skin aging by elaborating on biological markers. Furthermore, this paper presents a summary of recent research progress that reveals the correlation between telomere length and skin aging as well as model building methods; it also proposes telomere length as a potential indicator for predicting skin aging. Finally, anti-aging strategies based on telomere protection are discussed including drug therapy and lifestyle adjustments. This paper provides a systematic overview of the role played by telomeres in the field of skin aging for the first time, offering new perspectives and ideas for future prevention and treatment.},
}

*Skin Aging/physiology/genetics
Humans
*Telomere/metabolism
Skin/metabolism
Telomerase/metabolism
Telomere Homeostasis/physiology
Animals
Telomere Shortening

@article {pmid40155615,
year = {2025},
author = {Chen, XY and Lo, CKM and Chen, Q and Ho, FK and Leung, WC and Chan, KL},
title = {Associations between maternal adversity and health and children's telomere length.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {106},
pmid = {40155615},
issn = {2158-3188},
mesh = {Humans ; Female ; Pregnancy ; Longitudinal Studies ; Male ; Child, Preschool ; *Adverse Childhood Experiences ; Adult ; *Depression/genetics ; *Telomere/genetics ; Mothers/psychology ; Telomere Shortening/genetics ; Prenatal Exposure Delayed Effects/genetics ; Chronic Disease ; },
abstract = {Maternal adversity (e.g., adverse childhood experiences, ACEs) and health (e.g., depressive symptoms and chronic illness) negatively impact offspring's health. One possible mechanism is via premature/accelerated biological aging, as indicated in telomere length. In this 3-year longitudinal study, we examined the association between maternal adversity and health and children's buccal telomere length (bTL) at age 3. Data from 122 mother-child dyads were analyzed. Maternal history of ACEs and chronic illness were collected at baseline (during 20-24 weeks of gestation). Their depressive symptoms across three periods (during pregnancy, 4 weeks after childbirth, and 3 years after childbirth) were also collected. Children's TL were extracted from their buccal swab samples at age 3. The children's bTL was quantified using the quantitative PCR method and expressed in T/S ratio (the ratio of telomere repeats copy numbers to single-copy gene numbers). Results showed pregnant women experienced distinctive trajectories of depressive symptoms over time. Children of mothers with relapsing/remitting depressive symptoms had shorter bTL (β = -0.19, 95% CI = -0.14 to -0.005) than mothers who had low-stable symptoms. This finding remained significant even after accounting for maternal ACEs and chronic illness. Additionally, maternal ACEs, together with depressive symptoms, may affect children's bTL. This study provides relatively comprehensive evidence on the effects of maternal stressors, highlighting the relevance of maternal adversity and depressive symptom patterns as predictors of offspring telomere biology.},
}

Humans
Female
Pregnancy
Longitudinal Studies
Male
Child, Preschool
*Adverse Childhood Experiences
Adult
*Depression/genetics
*Telomere/genetics
Mothers/psychology
Telomere Shortening/genetics
Prenatal Exposure Delayed Effects/genetics
Chronic Disease

@article {pmid40151802,
year = {2025},
author = {Baylie, T and Jemal, M and Baye, G and Getinet, M and Amare, GA and Adugna, A and Abebaw, D and Hibstu, Z and Tegegne, BA and Gugsa, E and Adane, T and Getie, G and Ashenef, B and Sinamaw, D},
title = {The role of telomere and telomerase in cancer and novel therapeutic target: narrative review.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1542930},
pmid = {40151802},
issn = {2234-943X},
abstract = {Telomeres are dynamic complexes at the ends of chromosomes that are made up of protective proteins and tandem repeating DNA sequences. In the large majority of cancer cells, telomere length is maintained by telomerase, an enzyme that elongates telomeres. Telomerase activation is seen in the majority of cancer, which permits uncontrol cell proliferation. About 90% of human malignancies show telomere dysfunction and telomerase reactivation; as a result, telomerase activation plays a special role as a practically universal stage on the way to malignancy. This review understands the structural and functional of telomere and telomerase, mechanisms of telomerase activation in oncogenesis, biomarkers and therapeutic targets. Therapeutic strategies targeting telomerase, including antisense oligonucleotides, G-quadruplex stabilizers, immunotherapy, small-molecule inhibitors, gene therapy, Telomerase-Responsive Drug Release System, have shown promise in preclinical and clinical settings. Advances in telomere biology not only illuminate the complex interplay between telomeres, telomerase, and cancer progression but also open avenues for innovative, targeted cancer therapies.},
}

@article {pmid40149509,
year = {2025},
author = {Sater, MS and AlDehaini, DMB and Malalla, ZHA and Ali, ME and Giha, HA},
title = {A Perceived Dissociation Between Systemic Chronic Inflammation, Age, and the Telomere/Telomerase System in Type 2 Diabetes.},
journal = {Biomedicines},
volume = {13},
number = {3},
pages = {},
doi = {10.3390/biomedicines13030531},
pmid = {40149509},
issn = {2227-9059},
abstract = {Background: Chronic inflammation is associated with leukocyte telomere length (LTL) shortening and type 2 diabetes (T2D). The latter is also associated with LTL shortening, while the three variables are associated with aging. Objective: It is tempting to test whether inflammation, age, or both are behind the telomere system aberrations in diabetic patients. Methods: In this cross-sectional observational study, blood samples collected from 118 T2D patients were analyzed via ELISA to estimate the plasma levels of four inflammatory markers, IL6, IL8, TREM1, and uPAR, and the telomerase enzyme (TE). Moreover, the extracted DNA was used for the LTL estimation via qPCR and for single nucleotide polymorphisms (SNP) genotyping of TE genes (TERT, TERC, and ACYP2) via rtPCR. Results: The results showed no correlation between the levels of all tested inflammatory markers and the LTL, TE level, and age. There were no significant differences between the marker levels in diabetic patients in the four quartiles of the LTL and TE levels. Moreover, there were no significant differences in the levels of the markers between carriers of the different TE genotypes. Conclusions: There were no associations between the tested inflammatory markers' levels and the LTL, TE plasma levels, or age in T2D. Explanations for the dissociation between the above-known associations in T2D were proposed; however, the subject is worth further investigation.},
}

@article {pmid40149420,
year = {2025},
author = {Cruz-Ramos, JA and de la Mora-Jiménez, E and Llanes-Cervantes, BA and Damián-Mejía, MÁ},
title = {MicroRNAs in the Mitochondria-Telomere Axis: Novel Insights into Cancer Development and Potential Therapeutic Targets.},
journal = {Genes},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/genes16030268},
pmid = {40149420},
issn = {2073-4425},
support = {appac-2025//Universidad de Guadalajara/ ; },
mesh = {Humans ; *MicroRNAs/genetics ; *Neoplasms/genetics/metabolism/pathology ; *Mitochondria/metabolism/genetics ; *Telomere/genetics/metabolism ; Animals ; Gene Expression Regulation, Neoplastic ; },
abstract = {The mitochondria-telomere axis is recognized as an important factor in the processes of metabolism, aging and oncogenesis. MicroRNAs (miRNAs) play an essential function in this complex interaction, having an impact on aspects such as cellular homeostasis, oxidative responses and apoptosis. In recent years, miRNAs have been found to be crucial for telomeric stability, as well as for mitochondrial behavior, factors that influence cell proliferation and viability. Furthermore, mitochondrial miRNAs (mitomiRs) are associated with gene expression and the activity of the cGAS/STING pathway activity, linking mitochondrial DNA recognition to immune system responses. Hence, miRNAs maintain a link to mitochondrial biogenesis, metabolic changes in cancer and cellular organelles. This review focuses on the roles of a variety of miRNAs in cancer progression and their potential application as biomarkers or therapeutic agents.},
}

Humans
*MicroRNAs/genetics
*Neoplasms/genetics/metabolism/pathology
*Mitochondria/metabolism/genetics
*Telomere/genetics/metabolism
Animals
Gene Expression Regulation, Neoplastic

@article {pmid40148339,
year = {2025},
author = {Mannherz, W and Crompton, A and Lampl, N and Agarwal, S},
title = {Metabolic constraint of human telomere length by nucleotide salvage efficiency.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3000},
pmid = {40148339},
issn = {2041-1723},
mesh = {Humans ; *Telomerase/metabolism/genetics ; *Telomere/metabolism/genetics ; Animals ; *Telomere Homeostasis ; *Purine-Nucleoside Phosphorylase/metabolism/genetics ; Drosophila melanogaster/metabolism/genetics ; Deoxycytidine Kinase/metabolism/genetics ; Guanosine/metabolism ; Nucleotides/metabolism ; SAM Domain and HD Domain-Containing Protein 1/metabolism/genetics ; Hypoxanthine Phosphoribosyltransferase/metabolism/genetics ; Phosphotransferases (Alcohol Group Acceptor) ; },
abstract = {Human telomere length is tightly regulated and associated with diseases at either extreme, but how these bounds are established remains incompletely understood. Here, we developed a rapid cell-based telomere synthesis assay and found that nucleoside salvage bidirectionally constrains human telomere length. Metabolism of deoxyguanosine (dG) or guanosine via purine nucleoside phosphorylase (PNP) and hypoxanthine-guanine phosphoribosyltransferase to form guanine ribonucleotides strongly inhibited telomerase and shortened telomeres. Conversely, salvage of dG to its nucleotide forms via deoxycytidine kinase drove potent telomerase activation, the extent of which was controlled by the dNTPase SAMHD1. Circumventing limits on salvage by expressing Drosophila melanogaster deoxynucleoside kinase or augmenting dG metabolism using the PNP inhibitor ulodesine robustly lengthened telomeres in human cells, including those from patients with lethal telomere diseases. Our results provide an updated paradigm for telomere length control, wherein telomerase reverse transcriptase activity is actively and bidirectionally constrained by the availability of its dNTP substrates, in a manner that may be therapeutically actionable.},
}

Humans
*Telomerase/metabolism/genetics
*Telomere/metabolism/genetics
Animals
*Telomere Homeostasis
*Purine-Nucleoside Phosphorylase/metabolism/genetics
Drosophila melanogaster/metabolism/genetics
Deoxycytidine Kinase/metabolism/genetics
Guanosine/metabolism
Nucleotides/metabolism
SAM Domain and HD Domain-Containing Protein 1/metabolism/genetics
Hypoxanthine Phosphoribosyltransferase/metabolism/genetics
Phosphotransferases (Alcohol Group Acceptor)

@article {pmid40141057,
year = {2025},
author = {Huang, CM and Shen, YL and Ho, CL and Chen, TE and Hsia, HY and Songyang, Z and Chen, LY},
title = {C-Terminal Extended Domain-Independent Telomere Maintenance: Modeling the Function of TIN2 Isoforms in Mus musculus.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
pages = {},
pmid = {40141057},
issn = {1422-0067},
support = {AS-GCP-113-L02//Academia Sinica/ ; },
mesh = {Animals ; Mice ; *Protein Isoforms/genetics/metabolism ; *Telomere/metabolism/genetics ; *Telomere-Binding Proteins/metabolism/genetics ; Humans ; Telomere Homeostasis ; Fibroblasts/metabolism ; Alleles ; Alternative Splicing ; Protein Domains ; },
abstract = {TIN2 (TERF1 interacting nuclear factor 2) is a telomeric shelterin complex component, essential for telomere protection and early embryonic development in mammals. In humans, TIN2 isoforms arise from alternative splicing, but their specific roles in vivo remain unclear. Here, we explore TIN2 isoform functions in the laboratory mouse Mus musculus. Our comparative analysis of TIN2 protein sequences reveals that mouse TIN2 (TINF2) closely resembles the human TIN2L isoform, both of which harbor a C-terminal extended domain (CTED) absent from the human TIN2 small (TIN2S) isoform. To further characterize the functions of TIN2 isoforms, we generated a Tinf2 LD (long-form deficiency) allele in M. musculus encoding a short form of TINF2 lacking the CTED. Mice heterozygous or homozygous for this Tinf2 LD allele were viable, fertile, and showed no tissue abnormalities. Furthermore, protein product of Tinf2 LD allele localized to telomeres and maintained telomere integrity in mouse embryonic fibroblasts, demonstrating that the CTED is dispensable for telomere protection and normal development in mice. These findings indicate functional redundancy among TIN2 isoforms and underscore the utility of the Tinf2 LD model for uncovering isoform-specific mechanisms of telomere regulation.},
}

Animals
Mice
*Protein Isoforms/genetics/metabolism
*Telomere/metabolism/genetics
*Telomere-Binding Proteins/metabolism/genetics
Humans
Telomere Homeostasis
Fibroblasts/metabolism
Alleles
Alternative Splicing
Protein Domains

@article {pmid40145120,
year = {2024},
author = {Bordas-Martinez, J and Miedema, JR and Mathot, BJ and Seghers, L and Galjaard, RH and Raaijmakers, MHGP and Aalbers, AM and Wijsenbeek, M and Molina-Molina, M and Hellemons, ME},
title = {Outcomes of lung transplantation in patients with telomere-related forms of progressive fibrosing interstitial lung disease pulmonary fibrosis: A systematic review.},
journal = {JHLT open},
volume = {3},
number = {},
pages = {100054},
pmid = {40145120},
issn = {2950-1334},
abstract = {BACKGROUND: Lung transplantation (LTX) is the last life-extending option for patients with progressive fibrosing interstitial lung diseases (fILD). Between 12% and 71% of patients with fILD are patients with underlying telomere-dysfunction (trILD) related to pathogenic telomere-related gene (TRG) variants and/or short telomere length. TrILD patients tend to have earlier disease onset, faster progression, and worse prognosis causing them to be referred for LTX more often. Regarding LTX outcomes in trILD, there are contradictory reports on patient and graft survival, as well as numerous other outcomes. There is no consensus on whether trILD is associated with poorer outcomes after LTX and what considerations regarding candidacy are appropriate.

METHODS: We aimed to systematically review LTX outcomes of patients with trILD in comparison to those with non-trILD.

RESULTS: A systematic literature search yielded 13 studies that met the inclusion criteria including 933 LTX, 281 in trILD, and 652 in non-trILD. Despite large heterogeneity in the methodological study quality and reported outcomes among the studies, patient and graft survival after LTX in trILD did not evidently seem inferior to LTX in non-trILD. However, there may be increased risk of specific complications, such as cytopenias, airway complications, and cytomegalovirus-reactivation.

CONCLUSIONS: In summary, due to large heterogeneity in methodological study quality and reported outcomes, no firm conclusions can be drawn. Patient and graft survival do not seem unequivocally inferior in patients with trILD deemed eligible for LTX. On top of limited available high-quality data, specific patient selection and post-transplant management strategies may affect the currently acquired results. As such, differences may exist regarding transplant-related outcomes, which could require special attention and consideration. Further high-quality comparative studies on LTX outcomes in trILD are needed to draw final conclusions and provide recommendations regarding patient selection and post-transplantation management.},
}

@article {pmid40139649,
year = {2025},
author = {da Cruz, NFS and Sengillo, JD and Negron, CI and Berrocal, AM},
title = {Telomere Biology Disorders: Microvascular Abnormalities on Optical Coherence Tomography.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.03.027},
pmid = {40139649},
issn = {1879-1891},
abstract = {BACKGROUND AND OBJECTIVE: Telomere biology disorders (TBDs) are inherited conditions caused by telomere dysfunction, impacting systemic and ocular health. We aim to explore the role of optical coherence tomography angiography (OCTA) in identifying retinal microvascular abnormalities in TBDs.

DESIGN: Retrospective case series.

METHODS: The electronic medical records of pediatric patients with TBD at a tertiary referral eye center were reviewed from January 2019 to July 2023. OCTA images were reviewed for anomalies of the retinal vasculature.

RESULTS: In total, 13 eyes of 7 patients were included in the study. All patients were genetically confirmed to have TBD. The most common genetic variants were CTC1 (5 patients; 71.4%), ACD (1 patient; 14.3%) and RTEL1 (1 patient; 14.3%). On OCTA, all 13 eyes showed some degree of macular microvascular abnormality in both the SVC and DVC. The most common microvascular abnormality seen in the SVC was blood vessels anastomosis (11; 84.6%), and in the DVC was decreased vessel density (9; 69.2%).

CONCLUSIONS: OCTA imaging reveals a high prevalence of microvascular abnormalities in patients with TBD, highlighting its potential role in assessing retinal vascular changes associated with the disease.},
}

@article {pmid40138850,
year = {2025},
author = {Thirumoorthy, C and Rekha, RP and Deepa, M and Ram, U and Shalu, D and Venkatesan, U and Srikumar, BN and Anjana, RM and Balasubramanyam, M and Mohan, V and Saravanan, P and Govindaraj, P and Gokulakrishnan, K},
title = {Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms.},
journal = {Psychoneuroendocrinology},
volume = {176},
number = {},
pages = {107431},
doi = {10.1016/j.psyneuen.2025.107431},
pmid = {40138850},
issn = {1873-3360},
abstract = {AIM: A bidirectional link exists between depression and gestational diabetes mellitus (GDM). While telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) alterations have been reported either in GDM or depression, their predictive ability of GDM with coexisting depression remains unexplored. We, therefore, prospectively investigated the relationship of TL and mtDNA-CN in blood leukocytes during early pregnancy and explored their potential as predictive biomarkers for identifying the risk of developing GDM with depressive symptoms later in pregnancy.

METHODS: A nested cohort of 301 women with normal fasting glucose and without depressive symptoms in early pregnancy (<16 weeks) were selected from the STratification of Risk of Diabetes in Early Pregnancy (STRiDE) study. At 24-28 weeks (OGTT visit), a 75 g OGTT and PHQ-9 were performed. Women were categorized into four groups: NGT without depressive symptoms (n = 80), NGT with depressive symptoms (n = 105), GDM without depressive symptoms (n = 75), and GDM with depressive symptoms (n = 41). Blood leukocyte TL and mtDNA-CN were assessed using qRT-PCR.

RESULTS: TL and mtDNA-CN at early pregnancy were lower in women with GDM, depressive symptoms or both, compared to NGT without depressive symptoms at OGTT visit. TL and mtDNA-CN at early pregnancy were negatively associated with PHQ-9 score and OGTT blood glucose levels at OGTT visit after adjusting for age, pre-pregnancy BMI and family history of diabetes. Higher levels of both TL and mtDNA-CN in early pregnancy were associated with lower adjusted Relative Risk (aRR) (TL; aRR: 0.34; 95 % CI: 0.28, 0.41, mtDNA-CN; aRR: 0.83; 95 % CI: 0.74, 0.93) of GDM with depressive symptoms at OGTT visit.

CONCLUSION: Lower levels of TL and mtDNA-CN in early pregnancy are significantly associated with the later development of GDM and depressive symptoms at OGTT visit. Our findings indicate that early trimester TL and mtDNA-CN could be potential predictive biomarkers for predicting GDM with depressive symptoms and emphasize their potential for improved risk assessment so as to adopt preventive strategies targeting these conditions.},
}

@article {pmid40134806,
year = {2025},
author = {Liu, S and Xu, L and Cheng, Y and Liu, D and Zhang, B and Chen, X and Zheng, M},
title = {Methylation of the telomerase gene promoter region in umbilical cord blood of patients with gestational diabetes mellitus is associated with decreased telomerase expression levels and shortened telomere length.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1502329},
pmid = {40134806},
issn = {1664-2392},
mesh = {Humans ; *Telomerase/genetics ; *Diabetes, Gestational/genetics/blood ; Female ; Pregnancy ; *Promoter Regions, Genetic ; *DNA Methylation ; *Fetal Blood/metabolism ; Adult ; Case-Control Studies ; CpG Islands ; Prospective Studies ; Telomere Shortening/genetics ; Telomere/genetics ; Infant, Newborn ; Telomere Homeostasis ; },
abstract = {OBJECTIVE: This study speculates that gestational diabetes mellitus (GDM) may reduce fetal telomere length (TL),which may be related to modification of methylation in the promoter region of the telomerase (TE) gene promoter region.

METHODS: In this study, umbilical cord blood samples from patients with and without GDM (N = 100 each) were analyzed by prospective case-control. The TL, TE expression levels, and methylation levels of TERT and TERC gene promoter regions in two groups were measured. The significance of the methylation level of each CpG locus employed logistic regression analysis of R software, and the analysis of covariance (ANCOVA) was used to control the influence of confounding factors. Correlation analysis was performed by the Spearman.

RESULTS: The TL and TE expression levels of the offspring of GDM patients were decreased despite adjusting for PBMI, PWG, and TG. A total of two CpG islands were screened in the promoter region of the TERT gene and three fragments (TERT_2, TERT_3, and TERT_4) containing a total of 70 CpG sites were designed. Additionally, four CpG sites of the TERT gene in the GDM group (TERT_2_40, TERT_2_47, TERT_3_46, and TERT_3_212) showed increased methylation levels compared with the control group (all P < 0.05). In the promoter region of the TERC gene, one CpG island containing 19 CpG loci was screened and designed, and the methylation levels of the two CpG sites were significantly different in TERC_1_67 (0.65 ± 0.21 versus 0.57 ± 0.30; P = 0.040) and TERC_1_120 (0.68 ± 0.23 versus 0.59 ± 0.27; P = 0.014). The methylation levels of TERC gene fragments of GDM patients were significantly higher than those of the control group (0.69 ± 0.06 versus 0.65 ± 0.08, P = 0.001).

CONCLUSION: This study revealed that GDM may induce decreased TE expression by increasing the methylation levels of TE genes promoter region, thereby reducing the TL.},
}

Humans
*Telomerase/genetics
*Diabetes, Gestational/genetics/blood
Female
Pregnancy
*Promoter Regions, Genetic
*DNA Methylation
*Fetal Blood/metabolism
Adult
Case-Control Studies
CpG Islands
Prospective Studies
Telomere Shortening/genetics
Telomere/genetics
Infant, Newborn
Telomere Homeostasis

@article {pmid40133370,
year = {2025},
author = {Wan, L and Deng, C and Liu, B and Su, S and Zhang, Z and Jiang, Y and Zou, B and Liu, J and Du, Z and Zhang, Y and Chen, P and Xiao, W},
title = {Telomere-to-telomere genome assemblies of three silkworm strains with long-term pupal characteristics.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {501},
pmid = {40133370},
issn = {2052-4463},
mesh = {Animals ; *Bombyx/genetics ; *Genome, Insect ; *Telomere/genetics ; *Pupa/genetics ; },
abstract = {The domesticated silkworm (Bombyx mori) is both economically significant and a valuable model organism. However, challenges persist in silk production, particularly in preserving silkworm cocoons. The wild silkworm (Bombyx mandarina), a close relative, with long-term pupal characteristics, could address storage and industrial silk production issues. We conducted interspecies hybridization between domestic and wild silkworms, successfully introducing the long-pupal period trait into the domestic silkworm through genomic integration. Here, we presented the telomere-to-telomere genome assemblies of three silkworm strains (KA, L, and M) with long-term pupal characteristics. The genome assembly sizes ranged from 453.82 Mb to 461.92 Mb, with high contig N50 values and completeness. We predicted over 14,000 protein-coding genes and identified strain-specific fragments. This research enriches the domestic silkworm pan-genome project and provides a foundation for further genetic studies. By introducing the trait, we have for the first time reported a phenomenon of genomic introgression between domestic and wild silkworm, and have also opened up a new avenue for silkworm breeding.},
}

Animals
*Bombyx/genetics
*Genome, Insect
*Telomere/genetics
*Pupa/genetics

@article {pmid40132391,
year = {2025},
author = {Guillén-Vicente, I and Rodríguez-Íñigo, E and Guillén-Vicente, M and Samper, E and López-Alcorocho, JM and Orgaz, L and Fernández Jaén, TF and González, P and Abelow, S and García, I and de Pedro, N and Guillén-García, P},
title = {Comparing telomere lengths in chondrocytes from intact cartilage and those isolated from loose bodies.},
journal = {Tissue & cell},
volume = {95},
number = {},
pages = {102868},
doi = {10.1016/j.tice.2025.102868},
pmid = {40132391},
issn = {1532-3072},
abstract = {INTRODUCTION: Given the intrinsic connection between telomeres, cell replication, and aging, telomere length serves as a valuable biomarker for evaluating cell quality and viability. Studying telomeres can offer vital insights into the suitability of cells within articular loose bodies for autologous chondrocyte implantation in treating chondral lesions. The aim of this study was to assess cell quality by analyzing telomere profiles in isolated cells from loose bodies.

METHODS: Chondrocytes from loose bodies and intact cartilage from 3 patients with osteochondritis dissecans who underwent a High Density-Autologous Chondrocyte Implantation (HD-ACI), were isolated and cultured. Telomere length was determined by High-Throughput Quantitative Fluorescence in situ Hybridization (HT-Q-FISH). Percentile of telomere length, percentages of telomere length values (QuantiTel), percentages of cells with specific telomere values (QuantiCell) were estimated in each sample.

RESULTS: Percentile and QuantiTel showed lower telomere lengths in chondrocytes from loose bodies than in those from intact cartilage. QuantiCell demonstrated that the percentage of cells with shorter telomeres was higher in cells from loose bodies than in intact cartilage. Median telomere length was statistically higher in chondrocytes from intact biopsies than in loose bodies.

CONCLUSION: Chondrocytes isolated from loose bodies exhibits a telomere distribution shorter than those from intact cartilage.},
}

@article {pmid40129738,
year = {2025},
author = {Wang, L and Jia, KH},
title = {Editorial: Precision exploration of plant germplasm resources: breakthroughs and applications in telomere-to-telomere (T2T) genomics.},
journal = {Frontiers in plant science},
volume = {16},
number = {},
pages = {1573144},
doi = {10.3389/fpls.2025.1573144},
pmid = {40129738},
issn = {1664-462X},
}

@article {pmid40128533,
year = {2025},
author = {Bian, C and Hu, C and He, Z and Li, Z and Shi, Q},
title = {A complete telomere-to-telomere chromosome-level genome assembly of X-ray tetra (Pristella maxillaris).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {496},
pmid = {40128533},
issn = {2052-4463},
mesh = {*Telomere/genetics ; Animals ; *Genome ; Chromosomes ; },
abstract = {X-ray tetra (Pristella maxillaris) originates from the lower Amazon basin in South America. It is renowned for its strikingly transparent body, which has drawn significant interests in biomedical research and the world ornamental fish industry. Nevertheless, genomic resources for this interesting fish species remains scarce, hindering exploration of the molecular basis behind its unique transparency. To address this gap, we constructed the first complete telomere-to-telomere (T2T) chromosome-scale genome assembly of the X-ray tetra by integration of PacBio HiFi, ONT ultra-long, and Hi-C sequencing technologies. This haplotypic assembly spans approximately 1.1 Gb, with a contig N50 of 42.8 Mb. It is anchored onto 25 chromosomes, highlighting a complete set of 50 telomeres and 25 centromeres. We predicted 514.3 Mb of repetitive sequences and annotated 28,456 protein-coding genes in the assembled genome. Subsequent BUSCO analysis discovered high genome completeness (98.0%). This high-quality T2T genome assembly provides a valuable genetic resource for investigating the molecular mechanisms underlying transparency, and supporting in-depth studies on functional genomics, genetic diversity, and selective breeding for this economically important species.},
}

*Telomere/genetics
Animals
*Genome
Chromosomes

@article {pmid40122884,
year = {2025},
author = {Bian, C and Li, D and Wang, Y and He, Z and Chen, WT and Chong, CM and Zhou, H and Shi, Q},
title = {A telomere-to-telomere chromosome-scale genome assembly of glass catfish (Kryptopterus vitreolus).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {483},
pmid = {40122884},
issn = {2052-4463},
mesh = {Animals ; *Catfishes/genetics ; *Telomere/genetics ; *Genome ; *Chromosomes ; },
abstract = {Glass catfish (Kryptopterus vitreolus) is commonly distributed in several Asian countries, such as Thailand, Malaysia, and Indonesia. It is renowned for its near-transparent appearance, which has drawn considerable attention for biomedical research and the tropical ornamental fish industry. Here, we successfully constructed the first telomere-to-telomere (T2T) chromosome-scale genome assembly for glass catfish, by integration of PacBio HiFi, Nanopore ONT ultra-long, and Hi-C sequencing technologies. The haplotypic assembly covers approximately 687.7 Mb in length, featuring a high contig N50 of 21.3 Mb. This assembly was then anchored into 32 chromosomes, presenting a complete set of 64 telomeres and 32 centromeres. It was predicted with 252.4 Mb of repetitive sequences and annotated with a total of 24,696 protein-coding genes. Subsequent BUSCO analysis revealed high genome completeness (up to 96.4%). This high-quality T2T genome assembly not only provides a valuable genetic resource for investigating the molecular mechanisms underlying transparency, but also supports in-depth studies on functional genomics, genetic diversity, and selective breeding for this economically important fish species.},
}

Animals
*Catfishes/genetics
*Telomere/genetics
*Genome
*Chromosomes

@article {pmid40119960,
year = {2025},
author = {Pandey, A and Mancuso, T and Velsher, L and Kennedy, JA},
title = {Azacitidine and venetoclax for the treatment of AML arising from an underlying telomere biology disorder.},
journal = {Familial cancer},
volume = {24},
number = {2},
pages = {31},
pmid = {40119960},
issn = {1573-7292},
mesh = {Humans ; *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; *Leukemia, Myeloid, Acute/drug therapy/genetics ; *Azacitidine/therapeutic use ; Middle Aged ; *Sulfonamides/therapeutic use ; Male ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Telomere/drug effects ; },
abstract = {Telomere biology disorders (TBDs) are a group of genetic conditions characterized by defects in telomere maintenance leading to multisystemic organ involvement and a predisposition to hematologic malignancies. The management of patients with TBDs who develop acute myeloid leukemia (AML) presents a significant challenge due to their limited bone marrow reserve and non-hematopoietic organ dysfunction. We present the case of a 45-year-old patient with a previously unrecognized TBD who presented with AML. The patient's history of longstanding cytopenias, idiopathic avascular necrosis, and pulmonary fibrosis were suggestive of a TBD, which was confirmed through telomere length testing and the presence of a TERT variant. Due to his underlying TBD, he was treated with dose-reduced azacitidine and venetoclax, adapting the approach commonly employed in elderly, co-morbid AML patients ineligible for intensive chemotherapy. This resulted in a complete remission with incomplete count recovery that has persisted for greater than 12 months to date. Aside from prolonged myelosuppression, the patient tolerated the regimen well with minimal toxicity. To our knowledge, this is the first report of the successful utilization of azacitidine and venetoclax as an AML treatment modality in TBD patients and underscores the potential of this regimen as an effective non-intensive treatment strategy for high grade myeloid neoplasms arising in the context of inherited bone marrow failure syndromes.},
}

Humans
*Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
*Leukemia, Myeloid, Acute/drug therapy/genetics
*Azacitidine/therapeutic use
Middle Aged
*Sulfonamides/therapeutic use
Male
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Telomere/drug effects

@article {pmid40119470,
year = {2025},
author = {Wojcicki, JM and Epel, E and Lin, J and Tai, V and Schwarz, JM and Noworolski, SM and Erkin-Cakmak, A and Mulligan, K and Gugliucci, A and Lustig, RH},
title = {Leukocyte telomere length change in children with obesity in the context of an isocaloric fructose restriction intervention.},
journal = {Diabetology & metabolic syndrome},
volume = {17},
number = {1},
pages = {94},
pmid = {40119470},
issn = {1758-5996},
abstract = {BACKGROUND: Few studies have evaluated changes in leukocyte telomere length (LTL) over a short time period (e.g. 1 week). LTL shortening is accelerated by exposure to inflammation and reactive oxygen species (ROS) damage.

METHODS: In the context of an isocaloric fructose restriction study that was conducted with 43 Black and Latinx children over a 9-day period, we evaluated the relationship between metabolic health at baseline and metabolic changes and LTL at baseline and %LTL change over the follow-up period. Linear regression models were used to assess associations between metabolic correlates and LTL at baseline and LTL changes over 9 days.

RESULTS: Overall children lost - 0.05 ± 0.14 T/S units or - 2.98 ± 8.74% total change over the follow-up period. Higher concentrations of HDL-C, APO-AI and a greater % of large HDL-C at baseline were associated with reduced LTL attrition rates at day 10 (p < 0.01; p < 0.01 and p = 0.02 respectively). Increases in APO-AI over the follow-up period were associated with increased LTL attrition over the follow-up period (p = 0.03).

CONCLUSIONS: In this short term isocaloric fructose restriction study, LTL at baseline and changes in LTL over 9 days were associated with HDL-C and APO-AI and not with any other non-HDL-C lipids. Additional, larger studies are necessary to better understand the interplay between short term fructose restriction, LTL changes and HDL-C/APO-AI.},
}

@article {pmid40117028,
year = {2025},
author = {Ding, S and Gu, Q and Zhao, Z and Xie, Y and Wang, F and Liu, J and Li, H and Su, H and Wei, Q and Pi, S and Chen, F and Xiao, B and He, Y},
title = {Role of Glucose Metabolism in the Effects of Serum Metals on Telomere Length: Findings in Chinese Diabetic Population.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {40117028},
issn = {1559-0720},
abstract = {The effects of metal exposure on telomere length have attracted considerable attention, but definitive evidence is still lacking in the diabetic population. Thus, this study was conducted to explore the associations of metal mixture with telomere length and the mediated effects of glucose metabolism among the Chinese diabetic population. Eleven metals in serum and relative telomere length of leucocyte were quantified among 1516 diabetic population based on a large-scale diabetic retinopathy screening program in southern China. Multiple statistical models were used to evaluate the single and joint effects of metal mixture on telomere length. Moreover, to assess the mediating roles of glucose metabolism in the associations between metals and telomere length, mediation analyses were performed. In single-exposure models, serum levels of nickel and thallium were identified to be negatively associated with telomere length, while magnesium showed an inverted U-shaped association with telomere length. Consistent findings from three mixed-exposure analyses indicated that increased serum level of metal mixture was associated with decreased telomere length, with nickel playing a major role in the joint effects of the metals. Mediation analyses further revealed that the associations of nickel and metal mixture with telomere length were partially mediated by glycated hemoglobin, and the mediated proportions were 4.26% and 4.38%, respectively. Moreover, the associations between metals exposure and telomere length were observed to be more prominent in males. Our results indicated that exposure to metal mixture was associated with shortened telomere length, which may be partially mediated by glycated hemoglobin.},
}

@article {pmid40113806,
year = {2025},
author = {Jiang, C and Du, Y and Lou, Z and Zhang, Y and Wang, T},
title = {Telomere-to-telomere reference genome of Rhinogobio nasutus, an endangered endemic fish from the Yellow River.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {462},
pmid = {40113806},
issn = {2052-4463},
mesh = {Animals ; *Endangered Species ; *Genome ; China ; *Telomere/genetics ; Rivers ; Fishes/genetics ; },
abstract = {Rhinogobio nasutus is an endemic fish species native to the middle and upper reaches of the Yellow River in China, renowned for its high economic and nutritional value. However, due to overfishing, human activities, and environmental pollution, it is now critically endangered. This study presents the construction of a telomere-to-telomere (T2T) reference genome for R. nasutus by integrating PacBio HiFi reads, Oxford Nanopore Technologies and Hi-C data. The assembled genome has a total size of 953.38 Mb and is anchored to 25 autosomes. Multiple assessments confirmed the high quality of the genome in terms of mapping rate (99.77% and 99.85%), completeness (BUSCO: 99.31%), and accuracy (QV: 47.05 and 53.10). Functional annotation was achieved for 98.16% of the 24,677 protein-coding genes, with a BUSCO score of 99.81%. This work not only facilitates the genetic conservation of R. nasutus but also provides a valuable resource for related evolutionary studies.},
}

Animals
*Endangered Species
*Genome
China
*Telomere/genetics
Rivers
Fishes/genetics

@article {pmid40112135,
year = {2025},
author = {Feng, K and Liu, JL and Sun, N and Zhou, ZQ and Yang, ZY and Lv, H and Yao, C and Zou, JP and Zhao, SP and Wu, P and Li, LJ},
title = {Telomere-to-telomere genome assembly reveals insights into the adaptive evolution of herbivore-defense mediated by volatile terpenoids in Oenanthe javanica.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70062},
pmid = {40112135},
issn = {1467-7652},
support = {JBGS[2021]017//Jiangsu seed industry revitalization project/ ; CARS-24//Agriculture Research System of China/ ; 32102368//National Natural Science Foundation of China/ ; },
abstract = {Releasing large quantities of volatiles is a defense strategy used by plants to resist herbivore attack. Oenanthe javanica, a perennial herb of the Apiaceae family, has a distinctive aroma due to volatile terpenoid accumulation. At present, the complete genome and genetic characteristics of volatile terpenoids in O. javanica remain largely unclear. Here, the telomere-to-telomere genome of O. javanica, with a size of 1012.13 Mb and a contig N50 of 49.55 Mb, was established by combining multiple sequencing technologies. Comparative genome analysis revealed that O. javanica experienced a recent species-specific whole-genome duplication event during the evolutionary process. Numerous gene family expansions were significantly enriched in the terpenoid biosynthesis process, monoterpenoid, and diterpenoid biosynthesis pathways, which resulted in abundant volatile substance accumulation in O. javanica. The volatile terpenoids of O. javanica showed repellent effects on herbivores. Terpenoid biosynthesis was activated by wounding signals under exogenous stimuli. The TPS gene family was significantly expanded in O. javanica compared to those in other species, and the members (OjTPS1, OjTPS3, OjTPS4, OjTPS5, OjTPS7, OjTPS16, OjTPS18, OjTPS30 and OjTPS58) responsible for different terpenoid biosynthesis were functionally characterized. These results reveal the genome evolution and molecular characteristics of volatile terpenoids in the process of plant-herbivore interactions. This study also provides genomic resources for genetic and molecular biology research on O. javanica and other plants.},
}

@article {pmid40108243,
year = {2025},
author = {Wang, F and Bao, J and Zhang, H and Zhai, G and Song, T and Liu, Z and Han, Y and Yu, F and Zou, G and Zhu, Y},
title = {A telomere-to-telomere genome assembly of Chinese grain sorghum 654.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {460},
pmid = {40108243},
issn = {2052-4463},
mesh = {*Sorghum/genetics ; *Genome, Plant ; *Telomere/genetics ; East Asian People ; },
abstract = {The grain sorghum inbred line 654 serves as a parent for numerous Chinese commercial hybrids and recombinant inbred lines (RILs), which have played a pivotal role in the cloning of several agronomically important traits. In this study, we present a telomere-to-telomere (T2T) genome assembly of the inbred line 654 (728.81 Mb) using PacBio HiFi, ultra-long Oxford Nanopore Technology, and Hi-C sequencing data. The T2T genome assembly has high integrity (contains all of 10 centromeres and 20 telomeres without any gaps), high contiguity (contig N90: 52.02 Mb), high completeness (98.33% BUSCO completeness, 98.88% k-mer completeness, and LAI 24.38), and extremely low base error (3.37 × 10[-7], QV: 64.72). A total of 62.34% sequences were identified as repetitive, and rest region contained 44,399 protein-coding genes, of which 30,245 were functionally annotated. The gap-free T2T genome assembly enables the full picture of the potential translational genomics, and provides the highest resolution genetic map for future studies on genome evolution, structure variation, and the genetic control of agronomic traits in sorghum breeding.},
}

*Sorghum/genetics
*Genome, Plant
*Telomere/genetics
East Asian People

@article {pmid40107013,
year = {2025},
author = {Fostitsch, AJ and Schwarzer, G and Buchgeister, M and Surbeck, W and Lahmann, C and Spiegelhalder, K and Frase, L and Spieler, D},
title = {The association between sleep quality and telomere attrition: A systematic review and meta-analysis comprising 400,212 participants.},
journal = {Sleep medicine reviews},
volume = {80},
number = {},
pages = {102073},
doi = {10.1016/j.smrv.2025.102073},
pmid = {40107013},
issn = {1532-2955},
abstract = {Psychosocial stressors accelerate telomere attrition, a biomarker of cell aging, whereas good sleep is hypothesized to be a mitigating factor. However, methodological aspects - particularly underpowered studies, inconsistent findings, and multiple approaches to assessing sleep - demonstrate the need for a meta-analysis. After PROSPERO registration, we conducted a systematical search of the following databases until June 2024 to identify studies examining the relationship between sleep quality and telomere length in adult humans: CINAHL, Cochrane Library, MEDLINE, PsychINFO, PubMed, Web of Science, and Google Scholar. In total, 29 studies met inclusion criteria for the systematic review according to the preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA), 19 of which provided data that was appropriate for meta-analytic calculations. We identified the Pittsburgh sleep quality index (PSQI) global score (odds ratio (OR) 1.24, CI 95 % [1.03; 1.50], p = 0.02), sleep-related daytime impairments (OR 1.01 [1.00; 1.02], p = 0.04), and wake after sleep onset (WASO) time (OR 1.28 [1.12; 1.47], p < 0.01) as to be significantly associated with telomere attrition. Thus, the subtle telomere attrition-mitigating role of sleep has been demonstrated based on a sufficiently large body of data and defined aspects of sleep quality.},
}

@article {pmid40109908,
year = {2023},
author = {Bloom, SI and Tuday, E and Islam, T and Gogulamudi, VR and Lesniewski, LA and Donato, AJ},
title = {Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length.},
journal = {Aging biology},
volume = {1},
number = {},
pages = {},
pmid = {40109908},
issn = {2994-2578},
abstract = {Aging results in cellular damage that can induce cell cycle arrest known as cellular senescence. Endothelial cells are one of the first cell types to become senescent in advancing age and contribute to age-related cardiovascular diseases. Drugs known as senolytics reduce endothelial cell senescence in cell culture. From a translational perspective, a key question is whether this occurs in vivo and if remaining cells appear healthier and display fewer hallmarks of cellular aging. In this study, we treated old mice with the senolytic cocktail dasatinib and quercetin (D+Q) or a vehicle control. In 24-month-old mice, D+Q treatment reduced p21 gene expression in carotid artery endothelial cells, indicative of reductions in senescence. In lung endothelial cells, we examined DNA damage, telomere dysfunction (DNA damage signaling at telomeres), and telomere length, which are hallmarks of aging associated with senescence and other deleterious effects on cellular function. D+Q treatment resulted in fewer endothelial cells with DNA damage and dysfunctional telomeres. Surprisingly, D+Q reduced endothelial cell telomere length, yet this did not result in critically short telomeres and thus telomere dysfunction. Mice have longer telomeres than humans; therefore, future studies on the effect of senolytics on telomere length are warranted. Collectively, this study provides important evidence on the effect of senolytics, including that they clear senescent endothelial cells in vivo, which reduces DNA damage and telomere dysfunction. These data indicate that the clearing of senescent endothelial cells in old age leaves behind a population of cells that exhibit fewer hallmarks of vascular aging.},
}

@article {pmid40106431,
year = {2025},
author = {Lee Lynskey, M and Brown, EE and Bhargava, R and Wondisford, AR and Ouriou, JB and Freund, O and Bowman, RW and Smith, BA and Lardo, SM and Schamus-Hayes, S and Hainer, SJ and O'Sullivan, RJ},
title = {HIRA protects telomeres against R-loop-induced instability in ALT cancer cells.},
journal = {Cell reports},
volume = {44},
number = {3},
pages = {115497},
doi = {10.1016/j.celrep.2025.115497},
pmid = {40106431},
issn = {2211-1247},
}

@article {pmid40104396,
year = {2025},
author = {Xie, R and Chen, S and Li, X and Lan, Z},
title = {Assessment of the causal association between obstructive sleep apnea and telomere length: a bidirectional mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1294105},
pmid = {40104396},
issn = {1664-8021},
abstract = {BACKGROUND: A plethora of observational studies has established a significant correlation between Obstructive Sleep Apnea (OSA) and Telomere Length (TL). Nevertheless, a universal consensus on precise causal association and its directionality has not yet been achieved. To shed light on this, we employed Mendelian Randomization (MR) to investigate the bidirectional causal association between OSA and TL.

METHOD: Utilizing publicly accessible Genome-Wide Association Studies (GWAS) datasets, we procured genetic data pertinent to MR analysis. The study incorporated samples from both the OSA (n = 217,955) and TL (n = 472,174) cohorts. In the forward MR analysis, OSA served as the exposure variable and TL as the outcome. Conversely, the reverse MR analysis treated TL as the exposure and OSA as the outcome. We employed the Inverse variance weighted (IVW) as the primary methodology for MR analysis. To ensure the robustness of our MR findings, multiple sensitivity analyses were performed.

RESULTS: In the forward MR analysis, a negative correlation was indicated between OSA and TL (IVW: odds ratio (OR) = 0.964, 95% confidence interval (CI): 0.939-0.980, P = 0.006 < 0.05). However, no significant association was identified between TL and the risk of OSA in the reverse MR analysis (IVW: OR = 0.965, 95% CI: 0.870-1.070, P = 0.499 > 0.05).

CONCLUSION: Our study indicated a potential association between OSA and the increased risk of shorter TL, offering vital academic support for future clinical studies on this association.},
}

@article {pmid40102883,
year = {2025},
author = {Lu, Z and Chai, X and Li, S},
title = {Machine learning-based identification of telomere-related gene signatures for prognosis and immunotherapy response in hepatocellular carcinoma.},
journal = {Molecular cytogenetics},
volume = {18},
number = {1},
pages = {6},
pmid = {40102883},
issn = {1755-8166},
abstract = {Telomere in cancers shows a main impact on maintaining chromosomal stability and unlimited proliferative capacity of tumor cells to promote cancer development and progression. So, we targeted to detect telomere-related genes(TRGs) in hepatocellular carcinoma (HCC) to develop a novel predictive maker and response to immunotherapy. We sourced clinical data and gene expression datasets of HCC patients from databases including TCGA and GEO database. The TelNet database was utilized to identify genes associated with telomeres. Genes with altered expression from TCGA and GSE14520 were intersected with TRGs, and Cox regression analysis was conducted to pinpoint genes strongly linked to survival prognosis. The risk model was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, evaluation of the risk model focused on immune cell infiltration, checkpoint genes, drug responsiveness, and immunotherapy outcomes across both high- and low-risk patient groups. We obtained 25 TRGs from the overlapping set of 34 genes using Cox regression analysis. Finally, six TRGs (CDC20, TRIP13, EZH2, AKR1B10, ESR1, and DNAJC6) were identified to formulate the risk score (RS) model, which independently predicted prognosis for HCC. The high-risk group demonstrated worse survival outcomes and showed elevated levels of infiltration by Macrophages M0 and Tregs. Furthermore, a notable correlation was observed between the genes in the risk model and immune checkpoint genes. The RS model, derived from TRGs, has been validated for its predictive value in immunotherapy outcomes. In conclusion, this model not only predicted the prognosis of HCC patients but also their immune responses, providing innovative strategies for cancer therapy.},
}

@article {pmid40100529,
year = {2025},
author = {Jahn, K and Chatterjee, S and Sinke, C and Koberschinski, JJR and Jünemann, K and James, CE and Worschech, F and Marie, D and Altenmüller, E and Bär, C and Krüger, THC},
title = {An incidental finding during a brain plasticity study: substantial telomere length shortening after COVID-19 lockdown in the older population.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40100529},
issn = {2509-2723},
support = {100019E-170410//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 323965454//Deutsche Forschungsgemeinschaft/ ; BA 5631/5-1//Deutsche Forschungsgemeinschaft/ ; },
abstract = {The detrimental effects of lockdowns have already been proven by numerous studies, mainly using psychometric measurements. Since telomere shortening is a driver of aging and aging-associated disorders, including cognitive decline, the telomere length in the older population has been investigated in the current study. Measurements were taken over a 6-month period just before and during the 6 months that included the first lockdown. The cohort of 55 persons aged 64 to 70 years was investigated in the context of a study focusing on neuroplasticity. Participants were recruited in Germany and Switzerland and characterized by psychometric measurements concerning neurocognition and neuroplasticity. Telomere lengths were measured by real-time PCR-based LTL measurement. We found an impressive and significant decline in telomere lengths in the period that included the lockdown (2.33 (± 0.1) at T1 vs. 1.35 (± 0.1) at T2), whereas it was stable in the phase before the lockdown in the same individuals (T0 was 2.25 (± 0.1 S.E.M.) vs. T1, 2.33 (± 0.1)). Correlation of the sudden decrease revealed no linkage to health issues or general physical activity but was in trend related to a decline in the WHOQOL-BREF Social Score referring to the social interaction of the study participants. Our data support, at a biological level, the results of clinical and psychosocial studies showing the detrimental effects of lockdowns.},
}

@article {pmid40097825,
year = {2025},
author = {Paltoglou, G},
title = {Invited Commentary: "Is physical fitness associated with leukocyte telomere length in youth with type 1 diabetes?".},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {40097825},
issn = {1530-0447},
}

@article {pmid40097785,
year = {2025},
author = {Hu, G and Wang, Z and Tian, Z and Wang, K and Ji, G and Wang, X and Zhang, X and Yang, Z and Liu, X and Niu, R and Zhu, D and Zhang, Y and Duan, L and Ma, X and Xiong, X and Kong, J and Zhao, X and Zhang, Y and Zhao, J and He, S and Grover, CE and Su, J and Feng, K and Yu, G and Han, J and Zang, X and Wu, Z and Pan, W and Wendel, JF and Ma, X},
title = {A telomere-to-telomere genome assembly of cotton provides insights into centromere evolution and short-season adaptation.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40097785},
issn = {1546-1718},
abstract = {Cotton (Gossypium hirsutum L.) is a key allopolyploid crop with global economic importance. Here we present a telomere-to-telomere assembly of the elite variety Zhongmian 113. Leveraging technologies including PacBio HiFi, Oxford Nanopore Technology (ONT) ultralong-read sequencing and Hi-C, our assembly surpasses previous genomes in contiguity and completeness, resolving 26 centromeric and 52 telomeric regions, 5S rDNA clusters and nucleolar organizer regions. A phylogenetically recent centromere repositioning on chromosome D08 was discovered specific to G. hirsutum, involving deactivation of an ancestral centromere and the formation of a unique, satellite repeat-based centromere. Genomic analyses evaluated favorable allele aggregation for key agronomic traits and uncovered an early-maturing haplotype derived from an 11 Mb pericentric inversion that evolved early during G. hirsutum domestication. Our study sheds light on the genomic origins of short-season adaptation, potentially involving introgression of an inversion from primitively domesticated forms, followed by subsequent haplotype differentiation in modern breeding programs.},
}

@article {pmid40097392,
year = {2025},
author = {Romero-Zamora, D and Rogers, S and Low, RRJ and Page, SG and Lane, BJE and Kosaka, S and Robinson, AB and French, L and Lamm, N and Ishikawa, F and Hayashi, MT and Cesare, AJ},
title = {A CPC-shelterin-BTR axis regulates mitotic telomere deprotection.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2277},
pmid = {40097392},
issn = {2041-1723},
support = {1106241//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1162886//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; *Telomere/metabolism ; *Mitosis ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Aurora Kinase B/metabolism ; Phosphorylation ; Telomeric Repeat Binding Protein 1/metabolism ; Ataxia Telangiectasia Mutated Proteins/metabolism/genetics ; DNA Damage ; RecQ Helicases/metabolism/genetics ; DNA-Binding Proteins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Cell Cycle Proteins/metabolism/genetics ; Shelterin Complex/metabolism ; },
abstract = {Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes telomere linearity and a localized ATM-dependent telomere DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, and super-resolution imaging, we found that mitotic arrest-dependent (MAD) telomere deprotection requires the combined activities of the Chromosome passenger complex (CPC) on shelterin, and the BLM-TOP3A-RMI1/2 (BTR) complex on t-loops. During mitotic arrest, the CPC component Aurora Kinase B (AURKB) phosphorylated both the TRF1 hinge and TRF2 basic domains. Phosphorylation of the TRF1 hinge domain enhances CPC and TRF1 interaction through the CPC Survivin subunit. Meanwhile, phosphorylation of the TRF2 basic domain promotes telomere linearity, activates a telomere DDR dependent on BTR-mediated double Holliday junction dissolution, and leads to mitotic death. We identify that the TRF2 basic domain functions in mitosis-specific telomere protection and reveal a regulatory role for TRF1 in controlling a physiological ATM-dependent telomere DDR. The data demonstrate that MAD telomere deprotection is a sophisticated active mechanism that exposes telomere ends to signal mitotic stress.},
}

Humans
*Telomere/metabolism
*Mitosis
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Aurora Kinase B/metabolism
Phosphorylation
Telomeric Repeat Binding Protein 1/metabolism
Ataxia Telangiectasia Mutated Proteins/metabolism/genetics
DNA Damage
RecQ Helicases/metabolism/genetics
DNA-Binding Proteins/metabolism/genetics
Telomere-Binding Proteins/metabolism/genetics
Cell Cycle Proteins/metabolism/genetics
Shelterin Complex/metabolism

@article {pmid40097157,
year = {2025},
author = {Savage, SA},
title = {Telomeres and Human Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041684},
pmid = {40097157},
issn = {1943-0264},
abstract = {Telomeres, the long nucleotide repeats, and protein complex at chromosome ends, are central to genomic integrity. Telomere length (TL) varies widely between populations due to germline genetics, environmental exposures, and other factors. Very short telomeres caused by pathogenic germline variants in telomere maintenance genes cause the telomere biology disorders, a spectrum of life-threatening conditions including bone marrow failure, liver and lung disease, cancer, and other complications. Cancer predisposition with long telomeres is caused by rare pathogenic germline variants in components of the shelterin telomere protection protein complex and associated primarily with elevated risk of melanoma, thyroid cancer, sarcoma, and lymphoproliferative malignancies. In the middle, studies of the general population at risk of common illnesses, such as cardiovascular disease and cancer, have found statistically significant differences in TL but uncertain clinical applicability. This work reviews connections between telomere biology and human disease focusing on similarities and differences across the phenotypic spectrum.},
}

@article {pmid40097156,
year = {2025},
author = {Bettin, N and Vaurs, M and Decottignies, A},
title = {Epigenetics of Human Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041706},
pmid = {40097156},
issn = {1943-0264},
abstract = {Human telomeric heterochromatin is unusual in that it does not show the enrichment of canonical repressive histone marks H3K9me3 or H4K20me3 seen in constitutive heterochromatin. Instead, human telomeres exhibit both facultative heterochromatin and euchromatin marks, consistent with their epigenetically regulated transcription into TERRA noncoding RNA. Additionally, telomeric DNA is out of phase with the DNA helical repeat and has no nucleosome positioning signal. Yet, human telomeric DNA forms a columnar structure of tightly stacked nucleosomes, alternating with open states, and regulated by histone tails and shelterin protein binding. We discuss the proposed mechanisms regulating human telomeric chromatin and the consequences that telomeric chromatin properties have on various cellular processes, such as telomere transcription, the regulation of shelterin binding, and the activation of the alternative lengthening of telomeres mechanism. Together, we summarize current evidence on the combination of hetero- and euchromatic properties of human telomeres that may help explain their crucial protective functions and plasticity to regulate telomere maintenance pathways and damage signaling.},
}

@article {pmid40097153,
year = {2025},
author = {Zanella, E and Doksani, Y},
title = {In the Loop: Unusual DNA Structures at Telomeric Repeats and Their Impact on Telomere Function.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041694},
pmid = {40097153},
issn = {1943-0264},
abstract = {Telomeric repeats recruit the shelterin complex to prevent activation of the double-strand break response at chromosome ends. Thousands of TTAGGG repeats are present at each chromosome end to ensure telomere function. This abundance of G-rich repeats comes with the propensity to generate unusual DNA structures. The telomere loop (t-loop) structure, generated by strand invasion of the 3' overhang in the internal repeats, contributes to telomere function. G4-DNA is promoted by the stretches of G-rich repeats in a single-stranded form and may affect telomere replication and elongation by telomerase. The intramolecular homology can lead to the formation of internal loops (i-loops) via intramolecular recombination at sites of telomeric damage, which can promote the excision of telomeric repeats as extrachromosomal circular DNA. Shelterin promotes t-loops, counteracting the accumulation of pathological structures either directly or via the recruitment of specialized helicases. Here, we will discuss the current evidence for the formation of unusual DNA structures at telomeres and possible implications for telomere function.},
}

@article {pmid40097124,
year = {2025},
author = {Bollu, VS and Chen, YC and Zhang, F and Gowda, K and Amin, S and Sharma, AK and Schell, TD and Zhu, J and Robertson, GP},
title = {Managing Telomerase and Telomere Dysfunction in Acral Melanoma.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107700},
doi = {10.1016/j.phrs.2025.107700},
pmid = {40097124},
issn = {1096-1186},
abstract = {Acral Lentiginous Melanoma is a rare and aggressive subtype of melanoma that commonly affects the palms, soles, and nail beds. It is more prevalent in individuals with darker skin tones, including Asian, African, and Hispanic populations. Unlike cutaneous melanomas, acral melanoma is not associated with UV exposure and has a distinct genetic and molecular profile, underscoring the need for tailored research and treatment strategies. Standard treatments, such as surgery, chemotherapy, immunotherapy, and targeted therapies, have shown limited success for this melanoma subtype, highlighting the urgency of developing more effective interventions. Telomerase is an enzyme that extends telomeres and is a key target in acral melanoma which exhibits' high telomerase activity, driven by mutations in the telomerase reverse transcriptase TERT promoter, which contributes to uncontrolled tumor cell proliferation, cancer cell immortality, and resistance to conventional therapies. Therefore, targeting telomerase presents a promising therapeutic avenue for acral melanoma patients who do not respond well to current treatments. Several approaches for targeting telomerase deregulation have been developed, and their potential for the management of acral melanoma is discussed in this review. Specifically, the promise of telomerase-targeted therapies for acral melanoma is emphasized and explores how these strategies could improve outcomes for patients with this challenging skin cancer. By focusing on the role of telomerase in tumorigenesis and treatment resistance, telomerase-targeted strategies hold potential as a foundational component of therapies for acral melanoma, complementing existing approaches.},
}

@article {pmid40096055,
year = {2025},
author = {Sirovnik, J and Simon, R and Vogt, A and Barth, K and Smith, S and Waiblinger, S and Lühken, G and König von Borstel, U},
title = {Relative telomere length in dairy calves and dams undergoing two different methods of weaning and separation after three months of contact.},
journal = {PloS one},
volume = {20},
number = {3},
pages = {e0319156},
doi = {10.1371/journal.pone.0319156},
pmid = {40096055},
issn = {1932-6203},
mesh = {Animals ; Cattle ; *Weaning ; Female ; Telomere/genetics ; Behavior, Animal ; Telomere Homeostasis ; Stress, Physiological ; },
abstract = {Telomere length (i.e., the length of the repeated sequences of DNA at the end of chromosomes) is a promising indicator of overall stress. Our study aimed to compare the effects of a stress-inducing separation process between dams and their calves, with either a gradual or a nose-flap separation method after a three-months dam-calf contact since calving, on relative telomere length (RTL). Due to their nature, the nose-flap and gradual separation method have different effects on behaviour, stress hormone levels and physical development during and after dam-calf separation, which requires an overall measure of the weaning and separation stress during both procedures. We also investigated correlations between behavioural and other physiological stress indicators on RTL. We found no significant effect of the weaning and separation method on RTL in dairy calves after weaning and separation from their dams, but a tendency for shorter RTL in gradually separated dams compared to nose-flap separated dams. No correlations between behavioural and other physiological stress indicators and RTL were found, which may be due to a short interval between the two RTL measurement points. Future studies should aim to analyse the effect of various separation methods over a longer period and preferably include a non-separation group as reference.},
}

Animals
Cattle
*Weaning
Female
Telomere/genetics
Behavior, Animal
Telomere Homeostasis
Stress, Physiological

@article {pmid40087886,
year = {2025},
author = {Wu, G and Taylor, E and Youmans, DT and Arnoult, N and Cech, TR},
title = {Rapid dynamics allow the low-abundance RTEL1 helicase to promote telomere replication.},
journal = {Nucleic acids research},
volume = {53},
number = {5},
pages = {},
pmid = {40087886},
issn = {1362-4962},
support = {R35GM143108/NH/NIH HHS/United States ; DGE 2040434//GRFP/ ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Humans ; *DNA Helicases/metabolism/genetics ; *Telomere/metabolism ; *DNA Replication ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; S Phase/genetics ; Single Molecule Imaging ; Chromatin/metabolism ; Cell Nucleus/metabolism/genetics ; CRISPR-Cas Systems ; Protein Binding ; HeLa Cells ; G-Quadruplexes ; },
abstract = {Regulator of telomere length 1 (RTEL1) helicase facilitates telomere replication by disassembling DNA secondary structures, such as G-quadruplexes and telomeric loops (t-loops), at the ends of the chromosomes. The recruitment of RTEL1 to telomeres occurs during the S-phase of the cell cycle, but the dynamics of the process has not been studied. Here, we utilized CRISPR genome editing and single-molecule imaging to monitor RTEL1 movement within human cell nuclei. RTEL1 utilizes rapid three-dimensional diffusion to search for telomeres and other nuclear targets. Only 5% of the chromatin-bound RTEL1 is associated with telomeres at any time in the S-phase, but the telomere-bound RTEL1 has much more extended associations. This binding is enhanced by the interaction between RTEL1 and the telomeric protein TRF2 but is largely independent of RTEL1 ATPase activity. The absence of RTEL1 catalytic activity leads to severe defects in cell proliferation, slow progression out of S-phase, and chromosome end-to-end fusion events. We propose that the rapid diffusion of RTEL1 allows this low-abundance protein to explore the nucleus, bind TRF2, and be recruited to telomeres.},
}

Humans
*DNA Helicases/metabolism/genetics
*Telomere/metabolism
*DNA Replication
*Telomeric Repeat Binding Protein 2/metabolism/genetics
S Phase/genetics
Single Molecule Imaging
Chromatin/metabolism
Cell Nucleus/metabolism/genetics
CRISPR-Cas Systems
Protein Binding
HeLa Cells
G-Quadruplexes

@article {pmid40087268,
year = {2025},
author = {Winstanley, YE and Rose, RD and Sobinoff, AP and Wu, LL and Adhikari, D and Zhang, QH and Wells, JK and Wong, LH and Szeto, HH and Piltz, SG and Thomas, PQ and Febbraio, MA and Carroll, J and Pickett, HA and Russell, DL and Robker, RL},
title = {Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2527},
pmid = {40087268},
issn = {2041-1723},
support = {APP1130364//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP1117975//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP1194141//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 20669397//Channel 7 Children's Research Foundation (CRF)/ ; },
mesh = {Animals ; *Mitochondria/metabolism/drug effects/genetics ; Female ; *Telomere/metabolism/genetics ; Mice ; *Zygote/metabolism/drug effects ; *Fertilization ; Cell Nucleus/metabolism/drug effects ; Telomere Homeostasis/drug effects ; Blastocyst/metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Rotenone/pharmacology ; Pregnancy ; },
abstract = {The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.},
}

Animals
*Mitochondria/metabolism/drug effects/genetics
Female
*Telomere/metabolism/genetics
Mice
*Zygote/metabolism/drug effects
*Fertilization
Cell Nucleus/metabolism/drug effects
Telomere Homeostasis/drug effects
Blastocyst/metabolism/drug effects
Male
Mice, Inbred C57BL
Rotenone/pharmacology
Pregnancy

@article {pmid40082356,
year = {2025},
author = {Dragona, E and Gagos, S},
title = {Two-Replication Round, Telomere Strand-Specific, Chromosome Orientation Fluorescent In Situ Hybridization.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2906},
number = {},
pages = {177-188},
pmid = {40082356},
issn = {1940-6029},
mesh = {*Telomere/genetics ; *In Situ Hybridization, Fluorescence/methods ; *DNA Replication ; Humans ; *Sister Chromatid Exchange/genetics ; },
abstract = {Telomere strand-specific, two-replication-round, chromosome orientation fluorescence in situ hybridization (2R telomeric-CO-FISH) is a molecular cytogenetic protocol that allows simultaneous detection of genomic and telomeric sister chromatid exchanges along with telomeric intrachromosomal conservative break-induced replication. The combination of differential sister-chromatid and strand-specific telomeric labeling, provides information about intrachromosomal DNA recombinational events occurring in the last two consequent replication rounds of living cells grown in the presence of nucleic acid analogs. Despite a plethora of research applications, this methodology can be used to validate the extent of exposure to genotoxic agents and efficiency of recombinational DNA repair.},
}

*Telomere/genetics
*In Situ Hybridization, Fluorescence/methods
*DNA Replication
Humans
*Sister Chromatid Exchange/genetics

@article {pmid40082305,
year = {2025},
author = {Dratwa-Kuzmin, M and Lacina, P and Wysoczanska, B and Kilinska, D and Siemaszko, J and Sobczyk-Kruszelnicka, M and Fidyk, W and Solarska, I and Nasiłowska-Adamska, B and Skowronska, P and Bieniaszewska, M and Tomaszewska, A and Basak, G and Giebel, S and Bogunia-Kubik, K},
title = {Telomere length and telomerase reverse transcriptase gene polymorphism as potential markers of complete chimerism and GvHD development after allogeneic haematopoietic stem cell transplantation.},
journal = {Journal of cancer research and clinical oncology},
volume = {151},
number = {3},
pages = {109},
pmid = {40082305},
issn = {1432-1335},
support = {2018/31/B/NZ2/03065//Narodowym Centrum Nauki/ ; },
mesh = {Humans ; *Graft vs Host Disease/genetics/etiology ; *Telomerase/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Male ; Female ; Adult ; *Polymorphism, Single Nucleotide ; Middle Aged ; *Transplantation, Homologous ; Young Adult ; Adolescent ; Telomere/genetics ; Transplantation Chimera/genetics ; Aged ; Telomere Homeostasis/genetics ; Child ; },
abstract = {INTRODUCTION: Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase that maintains genome stability by maintaining telomere length (TL). The massive proliferation of donor cells in the recipient's body for engraftment results in accelerated telomere shortening. Genetic variability within the TERT gene affects telomerase activity, and was shown to influence of haematopoietic stem cell transplantation (HSCT) outcome. In the present study, we aimed to analyse the effect of recipient and donor TL and TERT single nucleotide polymorphism (SNP) on the occurrence of post-HSCT complications.

METHODS: Our study included 120 recipient-donor pairs. TERT promoter (TERTp) SNP (rs2853669) SNP variant was detected with the use of the LightSNiP typing assay employing real-time polymerase chain reaction (PCR) amplifications. Telomere length measurements were performed using qPCR test kits (ScienCell's Absolute Human Telomere Length Quantification qPCR Assay Kit [AHTLQ], Carlsbad, CA, USA).

RESULTS: The presence of TERTp rs2853669 T allele in the recipient was associated with a higher risk for acute graft-versus-host-disease (aGvHD) manifestation (p = 0.046) and a significantly shorter aGvHD-free survival (p = 0.041). The latter association was further confirmed in a Cox proportional hazards model (p = 0.043). However, no statistically significant association between telomere length and post-transplant complications was observed. Furthermore, we found that shorter TL characterized donors of patients with late complete chimerism at 180 day after HSCT (p = 0.011).

CONCLUSION: Our results suggest that recipient allele TERTp rs2853669 T is a marker of unfavourable outcome in the context of aGvHD. Shorter TL in donors could be associated with later achievement of complete chimerism.},
}

Humans
*Graft vs Host Disease/genetics/etiology
*Telomerase/genetics
*Hematopoietic Stem Cell Transplantation/adverse effects/methods
Male
Female
Adult
*Polymorphism, Single Nucleotide
Middle Aged
*Transplantation, Homologous
Young Adult
Adolescent
Telomere/genetics
Transplantation Chimera/genetics
Aged
Telomere Homeostasis/genetics
Child

@article {pmid40080344,
year = {2025},
author = {Alsurhi, TN and Shalaby, A and Al-Sinawi, S and Mabruk, M},
title = {Assessment of telomeres expression in melanoma and cutaneous squamous cell carcinoma: correlation with clinical parameters.},
journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {},
number = {},
pages = {},
pmid = {40080344},
issn = {1699-3055},
support = {IG/MED/ALIE/22/01//Sultan Qaboos University/ ; },
abstract = {BACKGROUND AND PURPOSE: The expression of the hTERT component of the human telomerase is elevated in different types of malignancies, including skin cancer. Early diagnosis of malignant melanoma is necessary to improve the prognosis of the disease. Although there are many diagnostic biomarkers for malignant melanoma, none is accurate, specific, and sensitive. The aim of the present study is to evaluate the expression rate and patterns of the hTERT component of human telomerase in melanoma and to compare this with squamous cell carcinoma as a common non melanoma skin cancer to investigate the potential of using telomerase as a molecular biomarker for the early diagnosis of this tumor. Additionally, the study compared the telomerase expression in these two tumor types with varying clinicopathological parameters.

METHODS: In this retrospective observational study, a total of 348 formalin-fixed paraffin-embedded tissue microarrays samples consisting of cutaneous melanoma (n = 189), squamous cell carcinoma (n = 115), and normal human skin samples (n = 44) were analyzed by immunohistochemistry for the expression of the hTERT component of human telomerase.

RESULTS: Out of 189 melanoma cases, 97 (51.3%) showed positive telomerase expression in contrast to detection of telomerase expression only in 3 out of 115 (2.6%) squamous cell carcinoma tissue samples. The telomerase was expressed only in 5 out of 44 normal human skins.

CONCLUSION: Our data indicate that telomerase expression is significantly more pronounced in melanoma compared to squamous cell carcinoma. These findings may support the potential utilization of telomerase as a biomarker for early diagnosis and monitoring of melanoma which can lead to timely treatment and enhances a better outcome.},
}

@article {pmid40079752,
year = {2025},
author = {Lee, SH and Song, DS and Kim, UC and Jee, SH and Lee, K},
title = {The causal relationship between telomere length and cancer risk: A two-sample Mendelian randomization.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1168},
pmid = {40079752},
issn = {1538-7755},
abstract = {BACKGROUND: Telomere length shortens with age and is associated with an increased risk of numerous chronic diseases. However, the causal direction between telomere length and cancer risk remains uncertain. This study aimed to assess the causal impact of telomere length on cancer risk using Mendelian randomization(MR) analysis.

METHODS: Genome-wide association studies(GWAS) from Singapore and China data, the Korean Cancer Prevention Study(KCPS)-II, the Korean Genome Epidemiologic Study(KoGES), and the Biobank of Japan(BBJ) were utilized. A two-sample MR study was performed using summary-level GWAS data from individuals of East Asian ancestry. Single nucleotide polymorphism(SNPs) associated with telomere length were used as instrumental variables.

RESULTS: Longer telomere length per 1SD increase due to germline genetic variants was associated with a higher risk of site-specific cancer. In the KCPS-II and KOGES, the strongest association was observed with thyroid cancer[OR 2.49(95%CI, 1.79-3.47), 2.27(1.49-3.46)], followed by lung cancer [OR 2.19(95%CI, 1.60-3.08) and 1.45(1.12-1.87)]. Similar results were observed in BBJ, with OR 2.92(95%CI, 1.75-4.88) for thyroid cancer and 2.04(1.41-2.94) for lung cancer. In histological subgroup analysis of KCPS-II, a significant relationship was found with lung adenocarcinoma [(OR 2.26(95%CI, 1.55-3.31)] but not with lung squamous cell carcinoma(1.21, 0.47-3.06). After removing outlier SNPs in the radial MR analysis, significant associations were identified for both lung adenocarcinoma [(OR 1.88(95%CI, 1.25-2.82)] and lung squamous cell carcinoma (2.29,1.05-4.98).

CONCLUSION: Our findings suggest that longer telomere length increases the risk of various cancers in East Asian populations.

IMPACT: Genetically determined longer telomere length may contribute to a risk of certain cancers.},
}

@article {pmid40075126,
year = {2025},
author = {Figueroa, D and Al Mamun, MM and Jung, DK and Li, G and Tan, ST and Jamshed, F and Butzin-Dozier, Z and Mertens, AN and Lin, J and Pitchik, HO and Parvin, K and Silvera, A and Fernald, LCH and Arnold, BF and Ali, S and Shoab, AK and Famida, SL and Akther, S and Rahman, MZ and Hossen, MS and Mutsuddi, P and Rahman, M and Unicomb, L and Kariger, P and Stewart, CP and Hubbard, AE and Benjamin-Chung, J and Dhabhar, FS and Luby, SP and Colford, JM and Naved, RT and Lin, A},
title = {Maternal experience of intimate partner violence, maternal depression, and parental stress are not associated with child telomere length in Bangladesh.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8499},
pmid = {40075126},
issn = {2045-2322},
support = {OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; K01AI136885//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; Bangladesh/epidemiology ; Female ; Male ; *Stress, Psychological ; *Intimate Partner Violence/psychology ; *Depression/epidemiology/genetics ; Infant ; Adult ; Child, Preschool ; Mothers/psychology ; Pregnancy ; Telomere/genetics ; Telomere Shortening ; Rural Population ; },
abstract = {Shorter telomere length (TL) is associated with an increased risk for developing chronic or age-related diseases in adults. The process of telomere shortening is accelerated in response to stress and is well characterized in adult populations from high-income countries. Prior studies suggest the relationship between stress, shorter TL, and disease risk initiates in early life. Nested within the WASH Benefits Bangladesh trial, we examined associations between parental stressors, including maternal exposure to intimate partner violence (IPV), maternal depressive symptoms, and parental perceived stress, and child TL in rural Bangladesh. We measured whole blood relative TL in 660 children at median age 14 months and 702 children at median age 28 months. We estimated mean differences between the 25th and 75th percentile or absence and presence of each exposure using generalized additive models. IPV during pregnancy was associated with more TL attrition between 14 and 28 months (- 0.32 (95% CI - 0.64, - 0.01), p-value 0.05). This association was not significant after correction for multiple comparisons. Other parental psychosocial stressors were not associated with child TL outcomes at 14 or 28 months of age in rural Bangladesh. Telomere biology during early-life development may vary across settings.},
}

Humans
Bangladesh/epidemiology
Female
Male
*Stress, Psychological
*Intimate Partner Violence/psychology
*Depression/epidemiology/genetics
Infant
Adult
Child, Preschool
Mothers/psychology
Pregnancy
Telomere/genetics
Telomere Shortening
Rural Population

@article {pmid40072904,
year = {2025},
author = {Han, H and Salinas, N and Barbey, CR and Jang, YJ and Fan, Z and Verma, S and Whitaker, VM and Lee, S},
title = {A telomere-to-telomere phased genome of an octoploid strawberry reveals a receptor kinase conferring anthracnose resistance.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf005},
pmid = {40072904},
issn = {2047-217X},
support = {#2022-51181-38328//National Institute of Food and Agriculture/ ; //Rural Development Administration/ ; },
mesh = {*Fragaria/genetics/microbiology ; *Telomere/genetics ; *Genome, Plant ; *Disease Resistance/genetics ; *Plant Diseases/genetics/microbiology ; Plant Proteins/genetics ; Polyploidy ; Colletotrichum/pathogenicity/genetics ; Haplotypes ; },
abstract = {BACKGROUND: Cultivated strawberry (Fragaria xananassa Duch.), an allo-octoploid species arising from at least 3 diploid progenitors, poses a challenge for genomic analysis due to its high levels of heterozygosity and the complex nature of its polyploid genome.

RESULTS: This study developed the complete haplotype-phased genome sequence from a short-day strawberry, 'Florida Brilliance' without parental data, assembling 56 chromosomes from telomere to telomere. This assembly was achieved with high-fidelity long reads and high-throughput chromatic capture sequencing (Hi-C). The centromere core regions and 96,104 genes were annotated using long-read isoform RNA sequencing. Using the high quality of the haplotype-phased reference genome, FaFB1, we identified the causal mutation within the gene encoding Leaf Rust 10 Disease-Resistance Locus Receptor-like Protein Kinase (LRK10) that confers resistance to anthracnose fruit rot (AFR). This disease is caused by the Colletotrichum acutatum species complex and results in significant economic losses in strawberry production. Comparison of resistant and susceptible haplotype assemblies and full-length transcript data revealed a 29-bp insertion at the first exon of the susceptible allele, leading to a premature stop codon and loss of gene function. The functional role of LRK10 in resistance to AFR was validated using a simplified Agrobacterium-based transformation method for transient gene expression analysis in strawberry fruits. Transient knockdown and overexpression of LRK10 in fruit indicate a key role for LRK10 in AFR resistance in strawberry.

CONCLUSIONS: The FaFB1 assembly along with other resources will be valuable for the discovery of additional candidate genes associated with disease resistance and fruit quality, which will not only advance our understanding of genes and their functions but also facilitate advancements in genome editing in strawberry.},
}

*Fragaria/genetics/microbiology
*Telomere/genetics
*Genome, Plant
*Disease Resistance/genetics
*Plant Diseases/genetics/microbiology
Plant Proteins/genetics
Polyploidy
Colletotrichum/pathogenicity/genetics
Haplotypes

@article {pmid40070565,
year = {2025},
author = {Song, Z and Yu, W and Yin, X},
title = {Identification of telomere-related gene subtypes and prognostic signatures in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1545913},
doi = {10.3389/fphar.2025.1545913},
pmid = {40070565},
issn = {1663-9812},
abstract = {BACKGROUND: Osteosarcoma (OS) is the prevalent primary bone cancer, with a high proclivity for local invasion and metastasis. Previous studies have indicated that telomeres are closely related to prognosis of cancer, but the significance of telomere-related features in OS remains uncertain. Thus, the goal of this work is to identified telomere-related subtypes based on the telomere-related genes (TRGs).

METHODS: The data of OS was collected from TARGET and Gene Expression Omnibus databases. Firstly, we identified the subtypes mediated by TRGs in OS. Subsequently, we analyzed the immune characteristics of telomeres-related subtypes in OS. Moreover, we built a telomere-related signature via univariate and LASSO Cox regression analyses, and analyzed the correlation of telomere-related signature with TME. Finally, we analyzed the expression of hub TRGs in OS.

RESULTS: We discovered that TRGs could distinguish OS patients into two telomeres-related subtypes (C1 and C2). The survival rate of OS patients in C2 was inferior to that of patients in C1. The scores of stromal, immune and ESTIMATES were observably increased, and tumor purity was decreased in C1 subtypes compared to C2 subtypes. Differentially expressed genes between C1 and C2 were highly enriched in immune-related pathways. Moreover, C1 and C2 subtypes had different immune characteristic. Furthermore, a telomere prognostic model including six genes (PDK2, PPARG, MORC4, SP110, TERT and MAP3K5) was established to predict the prognosis of OS patients. High-risk group was correlated with inferior prognosis of OS patients, and risk score model was correlated with TME. Finally, we discovered that expression of PDK2, PPARG, MORC4, SP110, TERT and MAP3K5 was significantly decreased in OS cells.

CONCLUSION: In conclusion, our study has uncovered the importance of TRGs in defining distinct subtypes of OS with different survival outcomes and immune contexts. The telomere-related signature we developed may serve as a valuable tool for prognosis prediction and could inform future therapeutic strategies targeting the TME in OS.},
}

@article {pmid40069335,
year = {2025},
author = {Rong, J and Liu, Q and Zhang, T and Lu, Y and Ye, Z and Teng, K and Luo, L and Wu, S and Zhao, L and Jin, W and Guan, Q and Li, Y and Qin, J and Cai, J and Zhang, Z},
title = {Associations of essential trace metals with telomere length in general population: a cross-sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8387},
pmid = {40069335},
issn = {2045-2322},
support = {AA22096026//The study was supported by the Major Science and Technology Projects in Guangxi/ ; 2019GXNSFGA245002//the Guangxi Natural Science Foundation for Innovation Research Team/ ; 82260629//the National Natural Science Foundation of China/ ; 81960583//he National Natural Science Foundation of China/ ; 20220120-2//Innovation Platform and Talent Plan in Guilin/ ; 2022-GKLEH-02//Xinghu Scholars Program of Guangxi Medical University，the Open Project Program of Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University/ ; KLLAD202304//Open Project of Key Laboratory of Longevity and Aging-related Diseases(Guangxi Medical University), Ministry of Education/ ; },
mesh = {Humans ; Middle Aged ; Male ; Female ; Cross-Sectional Studies ; Adult ; *Telomere ; *Trace Elements/blood ; Aged ; *Telomere Homeostasis ; Leukocytes/metabolism ; },
abstract = {This study investigated the relationship between essential plasma metals (Co, Cr, Cu, Mn, Mo, Se, Zn) and telomere length in 2,194 Chinese adults aged ≥ 30 years. Metal concentrations were measured using ICP-MS, and leukocyte relative telomere length (rTL) was assessed by qPCR. In the elderly, Cr and Mn were significantly positively correlated with rTL, while Mo, Zn, and Cu showed negative correlations. In the 30-59 age group, the overall metal mixture was significantly negatively associated with rTL (estimate = -0.069, P = 0.003), with Zn as the dominant contributor. In the elderly, the metal mixture was positively associated with rTL (estimate = 0.040, P = 0.031), with Cr and Mn as main contributors. The findings highlight the importance of maintaining adequate Cr and Mn levels in older adults, and the potential adverse impact of Cu, Mo, and Zn on telomere length.},
}

Humans
Middle Aged
Male
Female
Cross-Sectional Studies
Adult
*Telomere
*Trace Elements/blood
Aged
*Telomere Homeostasis
Leukocytes/metabolism

@article {pmid40068763,
year = {2025},
author = {Akopyan, K and Younis, M and Emtiazjoo, AM and Gries, C and Khamooshi, P and Rackauskas, M and Saha, BK},
title = {Short Telomere Syndrome in a patient with Primary Sjögren's Syndrome related Interstitial Lung Disease.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2025.03.003},
pmid = {40068763},
issn = {1538-2990},
abstract = {Interstitial lung disease (ILD) is a known complication of Primary Sjögren's syndrome (SS). We report the case of a 56-year-old man with a history of SS (SS-A positive) who was admitted with ILD exacerbation, causing respiratory failure requiring extracorporeal life support. Given the family history of rapidly progressive ILD and mixed connective tissue disease in his brother, the patient was tested for short telomere syndrome (STS) during hospitalization and found to have leukocyte telomere length (LTL) around the first percentile, suggesting the diagnosis of STS. The patient successfully underwent bilateral lung transplantation while being supported by venovenous extracorporeal membrane oxygenation (VV-ECMO). As STS has been associated with the development of ILD, the coexistence of STS and SS in our patient represents a unique scenario. This case also raises awareness of the connection between other connective tissue diseases (CTDs) and STS in patients diagnosed with ILD.},
}

@article {pmid40067965,
year = {2025},
author = {Thanaraj, TA and Abu-Farha, M and Albatineh, AN and Channanath, A and Melhem, M and Chandy, B and Anoop, E and Abubaker, J and Al-Mulla, F},
title = {Impact of Ethnicity on the Relationship Between Telomere Length and Metabolic Markers - a Multi-Ethnic Study from Kuwait.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgaf164},
pmid = {40067965},
issn = {1945-7197},
abstract = {OBJECTIVE: Telomere plays a critical role in maintaining genomic stability, and its length serves as a marker of cellular aging. Emerging evidence projects telomere length as a clinical risk factor for metabolic diseases. Our current study examines the associations between telomere length and demographic factors including metabolic health in a multi-ethnic cohort to provide insight into the impact of ethnicity on the potential use of telomere length as a biomarker for assessing diabetes risk.

METHODS: The cross-sectional study cohort comprised 2,083 individuals of Arab, South Asian, or Southeast Asian descent living in Kuwait. Telomere lengths were measured from peripheral venous blood DNA using qPCR-based techniques. Associations between telomere length and metabolic indicators (including BMI, being diabetic, HbA1c, FBG, and HOMA-IR) were analyzed using Spearman correlation and quantile regression, adjusting for covariates.

RESULTS: South Asian and Southeast Asian participants had significantly higher median telomere lengths than Arabs. Median telomere lengths varied significantly across sex, age tertiles, ethnicity, being diabetic, BMI, and HOMA-IR scores. Telomere length was negatively associated with being male (β=-0.49, 95% CI:[-0.85, -0.13]), diabetic (β=-0.77, 95% CI:[-1.25, -0.29]), age (β=-0.06, 95% CI:[-0.08, -0.04]), HOMA-IR (β=-1.01, 95% CI:[-1.43, -0.575]), BMI (β=-0.11, 95% CI:[-0.14, -0.083]), and HbA1c (β=-0.213, 95% CI:[-0.33, -0.096]). Negative correlations between telomere lengths and TG, HbA1c, FBG, insulin, and HOMA-IR levels were more highly significant in South Asians than in Arabs and Southeast Asians.

CONCLUSION: Our study underlines the significant influence of ethnicity on the the interplay between telomere length and metabolic health, and emphasizes the need to incorporate ethnic background when relating telomere biology to metabolic disorders. It further highlights the potential to incorporate telomere length into clinical risk factors for diabetes.},
}

@article {pmid40065531,
year = {2025},
author = {Chevalier, R and Murcia Pienkowski, V and Jullien, N and Caron, L and Pinard, PV and Magdinier, F and Robin, JD},
title = {Telomere Position Effect-Over Long Distances Acts as a Genome-Wide Epigenetic Regulator Through a Common Alu Element.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70027},
doi = {10.1111/acel.70027},
pmid = {40065531},
issn = {1474-9726},
support = {Inserm-First steps program UTelMe//Institut National de la Santé et de la Recherche Médicale/ ; A*Midex - pépinière d'excellence//Aix-Marseille Université/ ; Institute MarMaRa AMX-19-IET007//Aix-Marseille Université/ ; },
abstract = {Among epigenetic modifiers, telomeres represent attractive modulators of the genome in part through position effects. Telomere Position Effect-Over Long Distances (TPE-OLD) modulates gene expression by changes in telomere-dependent long-distance loops. To gain insights into the molecular mechanisms of TPE-OLD, we performed a genome-wide transcriptome and methylome analysis in proliferative fibroblasts and myoblasts or differentiated myotubes with controlled telomere lengths. By integrating omics data, we identified a common TPE-OLD dependent cis-acting motif that behaves as an insulator or enhancer. Next, we uncovered trans partners that regulate these activities and observed the consistent depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. Importantly, we confirmed our findings by unbiased comparisons to recent Human transcriptomic studies, including those from the Genotype-Tissue Expression (GTEx) project. We concluded that TPE-OLD acts at the genome-wide level and can be relayed by RBPJ bridging Alu-like elements to telomeres. In response to physiological (i.e., aging) or pathological cues, TPE-OLD might coordinate the genome-wide impact of telomeres through recently evolved Alu elements acting as enhancers in association with RBPJ.},
}

@article {pmid40064353,
year = {2025},
author = {Solh, T and Cevher, ŞC},
title = {The relationship between neuropsychiatric disorders and aging: A review on telomere length, oxidative stress, and inflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {115528},
doi = {10.1016/j.bbr.2025.115528},
pmid = {40064353},
issn = {1872-7549},
abstract = {Aging is the group of time-independent changes that occur in an organism and that ultimately end in death. The relationship between aging and neuropsychiatric disorders is complex. Not only does the incidence of several neuropsychiatric disorders rise with age, but also these disorders are linked with premature mortality and are even thought to be syndromes of accelerated biological aging. Oxidative stress, inflammation and telomere length are factors commonly used to assess biological aging. The purpose of this review is to sum up the existing information about the state of those factors in schizophrenia, depression, bipolar disorder and anxiety disorders, and to summarize the effects of treatment on telomere length in patients with those neuropsychiatric disorders. The main focus, however, is on telomere length seeing the highly controversial study results on this biomarker in neuropsychiatric disorders. There is no scientific consensus on the state of those factors in the mentioned neuropsychiatric disorders or on the effects of treatment on telomere length, thus further research is needed where confounding variables are controlled. Regarding telomere length, it is highly important to explore whether short telomeres lead to the development of neuropsychiatric disorders or vice versa, as it carries huge clinical potential.},
}

@article {pmid40061812,
year = {2025},
author = {Jia, KH and Li, G and Wang, L and Liu, M and Wang, ZW and Li, RZ and Li, LL and Xie, K and Yang, YY and Tian, RM and Chen, X and Si, YJ and Zhang, XY and Song, FJ and Li, L and Li, NN},
title = {Telomere-to-telomere, gap-free genome of mung bean (Vigna radiata) provides insights into domestication under structural variation.},
journal = {Horticulture research},
volume = {12},
number = {3},
pages = {uhae337},
pmid = {40061812},
issn = {2662-6810},
abstract = {Mung bean (Vigna radiata), an essential annual legume, holds substantial value in global agriculture due to its short growth cycle, low input requirements, and nutritional benefits. Despite extensive domestication, the genetic mechanisms underlying its morphological and physiological evolution remain incompletely understood. In this study, we present a gap-free, telomere-to-telomere genome assembly of the mung bean cultivar 'Weilv-9', achieved through the integration of PacBio HiFi, Oxford Nanopore, and high-throughput chromosome conformation capture (Hi-C) sequencing technologies. The 500-Mb assembly, encompassing 11 chromosomes and containing 28 740 protein-coding genes, reveals that 49.17% of the genome comprises repetitive sequences. Within the genome, we found the recent amplification of transposable elements significantly impacts the expression of nearby genes. Furthermore, integrating structural variation and single-nucleotide polymorphism (SNP) data from resequencing, we identified that the fatty acid synthesis, suberin biosynthetic, and phenylpropanoid metabolic processes have undergone strong selection during domestication. These findings provide valuable insights into the genetic mechanisms driving domestication and offer a foundation for future genetic enhancement and breeding programs in mung beans and related species.},
}

@article {pmid40061142,
year = {2025},
author = {Sasmita, DMA and Permana, KG and Aryandono, T and Heriyanto, DS and Anwar, SL},
title = {Shorter telomere length as a prognostic marker for survival and recurrence in breast cancer: a systematic review and meta-analysis.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002289},
pmid = {40061142},
issn = {2692-3114},
abstract = {BACKGROUND: Telomere length is a potential prognostic biomarker in breast cancer, but its clinical utility remains uncertain due to inconsistent findings across the literature. This systematic review and meta-analysis aims to evaluate the association between telomere length and breast cancer survival outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and recurrence-free survival (RFS).

METHODS: A systematic search of ten sources, including databases and publishers (JSTOR, Nature, ProQuest, PubMed, Sage Journals, ScienceDirect, Science, Scopus, Springer, and Wiley) was conducted to identify studies published up to December 31, 2023. Studies reporting associations between telomere length and survival outcomes in breast cancer patients were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) were extracted or calculated. Quality assessment was performed using the Newcastle-Ottawa Scale, and publication bias was evaluated using funnel plots, Egger's, and Begg's tests.

RESULTS: Nine studies involving 3,145 breast cancer patients were included. Shorter telomere length was significantly associated with increased recurrence risk (DFS/RFS) (pooled HR: 1.97; 95% CI: 1.04-3.74, P = 0.039), indicating a nearly twofold increase in risk. Trends toward worse OS (pooled HR: 1.60; 95% CI: 0.90-2.86, P = 0.110) and DSS (pooled HR: 1.09; 95% CI: 0.80-1.49, P = 0.565) were observed, but did not reach statistical significance. Additionally, shorter telomere length was significantly associated with premenopausal status (pooled OR: 1.34; 95% CI: 1.06-1.70, P = 0.01).

DISCUSSION: Shorter telomere length is associated with an increased risk of recurrence in breast cancer, highlighting its potential as a prognostic biomarker. However, further research is needed to standardize telomere length measurement methodologies and validate these findings across diverse populations and breast cancer subtypes.},
}

@article {pmid40058159,
year = {2025},
author = {Gadalla, SM and Katki, HA and Lai, TP and Auer, PL and Dagnall, CL and Bupp, C and Hutchinson, AA and Anderson, JJ and Mendez, KJW and Spellman, SR and Stewart, V and Savage, SA and Lee, SJ and Levine, JE and Saber, W and Aviv, A},
title = {Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndrome.},
journal = {EBioMedicine},
volume = {114},
number = {},
pages = {105641},
doi = {10.1016/j.ebiom.2025.105641},
pmid = {40058159},
issn = {2352-3964},
abstract = {BACKGROUND: Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes.

METHODS: We identified a cohort of 384 HCT recipients for early-stage leukaemia or myelodysplastic syndrome in the Blood and Marrow Transplant Clinical Trial Network protocol#1202 with blood samples collected three-month post-HCT. Blood samples from respective donors were available at the Centre for International Blood and Marrow Transplant Research biorepository. We used Cox proportional hazards models for statistical analyses.

FINDINGS: A better two-year overall survival (OS) was associated with longer donor LTL (adjusted-hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37-0.96, for LTL ≥6.7 kb vs LTL< 6.7 kb, p = 0.03), and higher LTL-3MS (HR = 0.52, 95% CI = 0.34-0.80, for LTL-3MS ≥ 230 vs < 230 bp, p = 0.003). Longer donor LTL was associated with a lower risk of non-relapse mortality (NRM; HR = 0.48, p = 0.05), while higher LTL-3MS was associated with lower relapse risk (HR for relapse risk = 0.53, p = 0.008). The adjusted 2-year cumulative risk of all-cause mortality was reduced by about half for patients with both donor LTL ≥6.7 kb and LTL-3MS ≥ 230 bp vs patients with neither characteristic (21% vs 41%, respectively; p < 0.0001).

INTERPRETATION: Selection of donors with longer LTL may improve HCT outcomes. Limited LTL shortening in recipients post-HCT may guide relapse prediction.

FUNDING: The NCI intramural research program and NIH grant U01AG066529.},
}

@article {pmid40057798,
year = {2025},
author = {Kasrineh, FA and Esmaeili, OS and Tavakoli, T and Khalili, P and Rajabi, Z and Vatankhah, H and Hajizadeh, MR and Mahmoodi, M and Hakimi, H and Jalali, Z},
title = {Prenatal irisin is inversely related to the term placental telomere length.},
journal = {BMC research notes},
volume = {18},
number = {1},
pages = {102},
pmid = {40057798},
issn = {1756-0500},
mesh = {Humans ; Female ; *Fibronectins/blood/metabolism ; Pregnancy ; Adult ; *Placenta/metabolism ; *Telomere/metabolism ; Young Adult ; Adolescent ; Infant, Newborn ; Biomarkers/blood ; Oxidative Stress ; Glutathione Peroxidase/blood/metabolism ; Superoxide Dismutase/blood/metabolism ; Telomere Homeostasis/physiology ; Cohort Studies ; },
abstract = {Irisin is a myokine mainly produced by skeletal muscle that impacts the body's systemic metabolism. It is connected to aging, telomere length, and oxidative stress markers in human adults and in vitro. The serum irisin concentration increases during pregnancy and has been linked to some birth outcomes like macrosomia. On the other hand, its inverse relation with the chance of pregnancy disorders like preeclampsia and gestational diabetes suggests a protective role for this myokine in pregnancy. It is suggested that irisin may exert its impact on pregnancy by affecting the placenta, which has not been studied yet. Here, we questioned whether prenatal serum irisin is related to placental markers, including telomere length and antioxidant activity. Research has shown that the status of these markers at birth can predict the predisposition to some chronic diseases later in life. We included 80 pregnant mothers (17-41 years old) and newborn dyads randomly selected from the enrolled participants of the Rafsanjan Birth Cohort Study (one of the five district areas of the PERSIAN birth cohort studies), who delivered at the Nik-Nafs Maternity Hospital in Rafsanjan in 2022. Irisin levels were measured in the mother's blood serum in pregnancy using ELISA. The relative telomere length and the GPX and SOD enzyme activities were measured in the term placenta using real-time PCR and colorimetric assays, respectively. We found an inverse relationship between the serum irisin levels during pregnancy and relative telomere length in the term placenta. Irisin level was not significantly associated with the activity of SOD and GPX enzymes. Therefore, our data does not support the protective role of prenatal irisin on the placental telomere shortening and oxidative stress. Future studies are warranted to assess more placental markers in relation to pregnancy irisin levels.},
}

Humans
Female
*Fibronectins/blood/metabolism
Pregnancy
Adult
*Placenta/metabolism
*Telomere/metabolism
Young Adult
Adolescent
Infant, Newborn
Biomarkers/blood
Oxidative Stress
Glutathione Peroxidase/blood/metabolism
Superoxide Dismutase/blood/metabolism
Telomere Homeostasis/physiology
Cohort Studies

@article {pmid40056294,
year = {2025},
author = {Chen, XB and Wang, L and Zhu, PY},
title = {Association between leukocyte telomere length and renal cell carcinoma: insight from Mendelian randomization study.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {285},
pmid = {40056294},
issn = {2730-6011},
abstract = {BACKGROUND: To investigate whether leukocyte telomere length (LTL) causally influences renal cell carcinoma (RCC) risk, this study applied Mendelian randomization (MR) analysis. Prior research examining LTL as a potential biomarker for RCC risk has yielded inconsistent findings.

METHODS: We obtained summary-level LTL data from the UK Biobank genome-wide association study (n = 472,174) and gathered RCC data from both the FinnGen Consortium (n = 289,360) and the International Agency for Research on Cancer (IARC) (n = 13,230). To estimate odds ratios (OR) and 95% confidence intervals (CI), we primarily used the inverse-variance-weighted (IVW) method. We assessed potential heterogeneity and horizontal pleiotropy through Cochran's Q test, MR-PRESSO, and MR-Egger. We then integrated the estimates from these sources using random-effects meta-analysis techniques.

RESULTS: Within the FinnGen Consortium, an increase in the genetically predicted LTL corresponds to an elevated risk of RCC development (IVW OR = 2.35; 95% CI 1.83-3.01; P = 2.07 × 10[-11]). This finding aligns with the outcomes observed in male patients within the IARC dataset (OR = 1.69; 95% CI 1.21-2.37; P = 0.002), although a consistent trend was not readily apparent among female patients. Sensitivity analyses validated the robustness of these findings. Upon pooling the results, a positive association between LTL and RCC risk was substantiated (OR = 1.96; 95% CI 1.52-2.52, p = 1.79 × 10[-7]). Furthermore, the MR Steiger test demonstrated that LTL was causal for RCC, not vice-versa, with P < 0.001.

CONCLUSION: Genetically determined longer LTL may increases RCC risk. Nevertheless, further research is essential to clarify the mechanisms driving this relationship.},
}

@article {pmid40057088,
year = {2025},
author = {Zhou, T and Huang, XJ and Cheng, YJ and Zhang, XY and Wang, XJ and Li, ZH},
title = {Telomere-to-telomere genome and multi-omics analysis of Prunus avium cv. Tieton provides insights into its genomic evolution and flavonoid biosynthesis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {141809},
doi = {10.1016/j.ijbiomac.2025.141809},
pmid = {40057088},
issn = {1879-0003},
abstract = {The European sweet cherry (Prunus avium) is highly valued for its superior quality, delectable taste, and robust stress resistance, leading to its extensive cultivation in the world. However, the previous incomplete genome assemblies have impeded its evolution and genetic regulation studies. In this study, we generated a Telomere-to-Telomere gap-free genome assembly of P. avium cv. Tieton, using advanced sequencing technologies. The assembled genome comprises eight pseudochromosomes with a genome size of 342.23 Mb and a contig N50 of 40.66 Mb. Comparative genomic analysis identified several unique stress resistance-related genes, possibly associated with the species' environmental adaptation. The integrative analyses of genomics, transcriptomes and metabolomes identified some key structural genes and metabolites crucial to flavonoid biosynthesis of sweet cherry. Our analyses revealed that 85 flavonoid metabolites, which are highly differentially accumulated among five tissues (flesh, stem, leaf, bud, and seed) of cherry. Interestingly, eight abundant flavonoids (Narcissoside, Typhaneoside, Myricetin 3-0-galactoside, Diosmin, Neohesperidin, Liquiritin apioside, 5,6,7-Trimethoxyflavone and Oroxin B) were highly accumulated in cherry flesh tissues. The gene-metabolite correlation analysis revealed that seven genes (HTC8, HTC6, CYP75B1_9, CYP75B1_10, 4CL1, DFR1, and FLS1) significantly regulated flavonoid accumulation in cherry flesh. Additionally, some structural genes (4CL6, PAL3, CYP75A2, F3H1, CYP75B1_8, and CYP75B1_10) were identified in the flavonoid biosynthetic pathway and were highly expressed, aligning with high flavonoid metabolite content in cherry flesh. These identified genes and metabolites are likely pivotal in conferring sweet cherry's stress resistance and high-quality traits. These findings offer deep insights into the mechanisms of genomic evolution and flavonoid biosynthesis, which also lay a solid foundation for further function genomics studies and breeding improvement in cherry.},
}

@article {pmid40048909,
year = {2025},
author = {Qin, N and Sheng, Y and Shao, Y and Liao, Q and Huang, D and Li, J and Li, J and Liu, H and Peng, Y and Qiu, X and Li, H},
title = {Associations between prenatal phthalate exposure and newborn telomere length: Effect modification by infant sex.},
journal = {Ecotoxicology and environmental safety},
volume = {292},
number = {},
pages = {117977},
doi = {10.1016/j.ecoenv.2025.117977},
pmid = {40048909},
issn = {1090-2414},
abstract = {BACKGROUND: Phthalates are endocrine-disrupting chemicals (EDCs) ubiquitously present in the environment. There are limited studies on the impact of phthalate exposure during the gestational period on neonatal telomere length.

OBJECTIVES: The aim of this study is to investigate the correlation between maternal serum phthalate concentrations in early pregnancy and neonatal telomere length and whether this correlation exhibits sex-specificity.

METHODS: Between September 2015 and April 2018, 474 pregnant women were selected from the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum samples from early pregnancy were measured for levels of five phthalates and four phthalate metabolites. Umbilical cord blood samples were collected to measure telomere length. The correlations between prenatal phthalate exposure and infant telomere length were assessed using multiple linear regression, Bayesian kernel machine regression (BKMR), quantile g-computation (qg-comp), and restricted cubic spline (RCS) models.

RESULTS: Multiple linear regression analyses revealed that per 2.7-fold increase in the concentration of butyl benzyl phthalate (BBP) and mono-ethyl phthalate (MEP), neonatal telomere length decreased by 2.66 % (95 % CI: -5.20 %, -0.05 %) and 3.43 % (95 % CI: -6.46 %, -0.30 %), respectively. Conversely, per 2.7-fold increase in di-butyl phthalate (DBP) concentration corresponded to a 3.01 % (95 % CI: 0.19 %, 5.91 %) increase in neonatal telomere length. Sex-stratified analyses demonstrated that BBP (percent change: -3.60 %; 95 % CI: -6.91 %, -0.18 %); mono-butyl phthalate (MBP) (percent change: -4.13 %; 95 % CI: -7.14 %, -1.01 %) and MEP (percent change: -7.66 %, 95 % CI: -11.53 %, -3.62 %) were inversely associated with neonatal telomere length in female infants only. Neonatal sex significantly modified the association between MEP exposure and neonatal telomere length (P-value for interaction = 0.018). Phthalate mixture was inversely associated with neonatal telomere length in female infants but not in male infants in qg-comp and BKMR models.

CONCLUSION: Our study suggests that maternal exposure to phthalates is linked to shorter telomere length in neonates, especially in female infants.},
}

@article {pmid40044947,
year = {2025},
author = {Huang, X and Huang, L and Lu, J and Cheng, L and Wu, D and Li, L and Zhang, S and Lai, X and Xu, L},
title = {The relationship between telomere length and aging-related diseases.},
journal = {Clinical and experimental medicine},
volume = {25},
number = {1},
pages = {72},
pmid = {40044947},
issn = {1591-9528},
support = {2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 4285C50223204005//Hangzhou Normal University/ ; 4285C50223204005//Hangzhou Normal University/ ; },
mesh = {Humans ; *Aging/genetics ; *Telomere Shortening ; *Telomere ; Cellular Senescence/genetics ; Telomere Homeostasis ; },
abstract = {The intensifying global phenomenon of an aging population has spurred a heightened emphasis on studies on aging and disorders associated with aging. Cellular senescence and aging are known to be caused by telomere shortening. Telomere length (TL) has emerged as a biomarker under intense scrutiny, and its widespread use in investigations of diseases tied to advancing age. This review summarizes the current knowledge of the association between telomeres and aging-related diseases, explores the important contribution of dysfunctional telomeres to the development and progression of these diseases, and aims to provide valuable insights for the development of novel therapeutic strategies.},
}

Humans
*Aging/genetics
*Telomere Shortening
*Telomere
Cellular Senescence/genetics
Telomere Homeostasis

@article {pmid40043570,
year = {2025},
author = {Gonçalves, JPB and Chile, T and de Paula, VJR and Teixeira, MZ and Ribeiz, SR and Schalling, M and Busatto Filho, G and Lucchetti, G and Vallada, H},
title = {Exploring the relationship between religiosity and telomere length in older individuals.},
journal = {Journal of psychosomatic research},
volume = {191},
number = {},
pages = {112085},
doi = {10.1016/j.jpsychores.2025.112085},
pmid = {40043570},
issn = {1879-1360},
abstract = {OBJECTIVES: Although telomere length is an established marker of biological aging, the impact of religious beliefs on telomere length remains uncertain.

METHODS: This cross-sectional study investigated the relationship between religiosity and telomere length among senior Brazilians, aged 60 and older. The study examined the association between organizational, non-organizational, and intrinsic religiosity with telomere length, adjusting for sociodemographic, mental, physical health, and medication. Hierarchical linear regression models were used.

RESULTS: 821 participants (62.2 % female, mean age 68.9 years, SD = 6.48) were studied. Female gender and younger age were linked to longer telomeres, but no significant associations were found between religious beliefs and telomere length in adjusted or unadjusted models.

CONCLUSIONS: This study found no evidence of an association between religiosity and telomere length among older Brazilian adults. While prior research highlights religiosity's positive health effects, its direct influence on telomere length remains unclear, warranting further exploration.},
}

@article {pmid40038488,
year = {2025},
author = {Le Bras, A},
title = {A new mouse model with human-like telomeres.},
journal = {Lab animal},
volume = {54},
number = {3},
pages = {63},
doi = {10.1038/s41684-025-01530-7},
pmid = {40038488},
issn = {1548-4475},
}

@article {pmid40035723,
year = {2025},
author = {De Benedittis, G and Latini, A and Morgante, C and Bonini, C and Cela, E and Kroegler, B and Luciano, A and Chiocchi, M and Cavalli, F and Ora, J and Rogliani, P and Novelli, G and Ciccacci, C and Chimenti, MS and Conigliaro, P and Borgiani, P},
title = {Alteration of telomere length and mtDNA copy number in interstitial lung disease associated with rheumatoid arthritis.},
journal = {Autoimmunity},
volume = {58},
number = {1},
pages = {2473741},
doi = {10.1080/08916934.2025.2473741},
pmid = {40035723},
issn = {1607-842X},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/complications ; *DNA, Mitochondrial/genetics ; Female ; Male ; *Lung Diseases, Interstitial/genetics ; Middle Aged ; *DNA Copy Number Variations ; Aged ; *Telomere/genetics ; Adult ; DNA-Binding Proteins/genetics ; Telomere Shortening ; Telomere Homeostasis/genetics ; Case-Control Studies ; Gene Dosage ; },
abstract = {Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The inflammatory response in lung disease is characterized by severe oxidative stress, which enhances cellular senescence. Telomeric shortening and mitochondria dysregulation represent two hallmarks of cellular senescence. The maintenance of telomere length (TL) and mitochondrial DNA (mtDNA) copy number is preserved by many proteins, such as TERF1 and TFAM, respectively. Our aim was to evaluate the TL, the mtDNA copy number and the expression of two regulator gene factors in RA patients with (RA-ILD) and without lung involvement (RA-NILD). Eighty-five RA patients and 21 healthy subjects were enrolled. Relative TL, mtDNA copy number, and expression analysis of TERF1 and TFAM genes were measured using qPCR assay. All RA patients present a statistically significant telomere shortening; in particular, RA-ILD patients show shorter TL compared to both controls and RA-NILD. Patients with Usual Interstitial Pneumonia pattern show a more evident shortening of TL. Lastly, both RA-ILD and RA-NILD patients present a significant decrease in mtDNA copy number compared to controls. The analysis of regulatory genes showed an increase in TERF1 expression in RA patients compared to controls, also after stratification in the two subgroups, and a decrease in TFAM expression in RA patients compared to controls. These results show that the alteration of TL and mtDNA copy number in RA patients is more evident in the presence of ILD. The hypothesis is that, in these patients, oxidative stress could accelerate the shortening of telomeres and the decrease of mtDNA copy number.},
}

Humans
*Arthritis, Rheumatoid/genetics/complications
*DNA, Mitochondrial/genetics
Female
Male
*Lung Diseases, Interstitial/genetics
Middle Aged
*DNA Copy Number Variations
Aged
*Telomere/genetics
Adult
DNA-Binding Proteins/genetics
Telomere Shortening
Telomere Homeostasis/genetics
Case-Control Studies
Gene Dosage

@article {pmid40029527,
year = {2025},
author = {Jebaraj, BMC},
title = {Quantification of Telomere Length in Peripheral Blood Mononuclear Cells Using Quantitative Polymerase Chain Reaction.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2909},
number = {},
pages = {257-267},
pmid = {40029527},
issn = {1940-6029},
mesh = {*Leukocytes, Mononuclear/metabolism ; Humans ; *Telomere/genetics ; *Real-Time Polymerase Chain Reaction/methods ; Telomere Homeostasis ; },
abstract = {Telomeres are crucial biomarkers of cellular aging and health, providing insights into various physiological and pathological processes. Large variety of methods are described for telomere length measurements, each with their own advantages and disadvantages. This chapter explains a quantitative polymerase chain reaction (qPCR)-based method for measuring telomere length in peripheral blood mononuclear cells (PBMCs), with special focus on ways to limit variability between qPCR run and improve comparability of telomere length values. With methodology of relative and absolute quantification, troubleshooting tips, and other guidelines, this chapter serves as a resource for researchers to benefit from this cost-effective and high-throughput assay.},
}

*Leukocytes, Mononuclear/metabolism
Humans
*Telomere/genetics
*Real-Time Polymerase Chain Reaction/methods
Telomere Homeostasis

@article {pmid40028272,
year = {2025},
author = {Huang, W and Wang, W and Dong, TZ},
title = {Telomere Maintenance-Related Genes are Essential for Prognosis in Breast Cancer.},
journal = {Breast cancer (Dove Medical Press)},
volume = {17},
number = {},
pages = {225-239},
pmid = {40028272},
issn = {1179-1314},
abstract = {OBJECTIVE: Telomere maintenance mechanism significantly impacts the metastasis, progression, and survival of breast cancer (BC) patients. This study aimed to investigate the role of telomere maintenance-related genes (TMRGs) in BC prognosis and to construct a related prognostic model.

METHODS: Differentially expressed genes were identified from the TCGA-BC cohort, and functional enrichment analysis was conducted. TMRGs were sourced from the literature and intersected with DEGs. Candidate genes were selected using machine learning algorithms, including Lasso Cox, Random Forest, and XGBoost. Multivariate Cox regression analysis was conducted to construct a prognostic model and identify hub genes. Subsequent analyses included survival analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and drug sensitivity analysis of the hub genes. Finally, in vitro experiments were conducted to validate the expression of the hub genes.

RESULTS: A total of 1329 differentially expressed TMRGs were analyzed, with 128 significantly associated with overall survival. Machine learning identified 7 prognosis-related TMRGs: MECP2, PCMT1, PFKL, PTMA, TAGLN2, TRMT5, and XRCC4. These genes were used to construct a prognostic model, with MECP2, PCMT1, PFKL, TAGLN2, and XRCC4 as harmful factors, while PTMA and TRMT5 were protective. The model demonstrated a significant prognostic value (AUC: 0.81, 0.72, 0.69 for 1-, 3-, and 5-year, respectively). Survival analysis confirmed the prognostic relevance of these genes, and GSEA highlighted their roles in oxidative phosphorylation, glycolysis, and PI3K/AKT/mTOR signaling.

CONCLUSION: The study identified 7 key TMRGs with significant prognostic value in BC. The constructed model effectively stratifies patient risk, providing a foundation for targeted therapies and personalized treatment strategies.},
}

@article {pmid40027133,
year = {2025},
author = {Zheng, JH and Shi, D and Chen, YJ and Liu, JP and Zhou, Z},
title = {Develop a prognostic and drug therapy efficacy prediction model for hepatocellular carcinoma based on telomere maintenance-associated genes.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1544173},
pmid = {40027133},
issn = {2234-943X},
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) poses a substantial global health challenge because of its grim prognosis and limited therapeutic options. Telomere maintenance mechanisms (TMM) significantly influence cancer progression, yet their prognostic value in HCC remains largely unexamined. This research aims to establish a telomere maintenance-associated genes(TMGs)-based prognostic model using transcriptomic and clinical data to evaluate its effectiveness in predicting patient outcomes in HCC.

METHODS: The identified differentially expressed genes (DEGs) were derived from the analysis of transcriptomic and clinical information sourced from the database of the Cancer Genome Atlas (TCGA) and were cross-referenced with TMGs. Candidate risk factors were initially assessed using univariate Cox regression, subsequently followed by LASSO, and then refined through multivariate Cox regression to establish a risk prediction model. This model's predictive accuracy was validated through Kaplan-Meier(K-M) survival analysis, with external validation in the Gene Expression Omnibus (GEO) dataset. Additionally, a nomogram incorporating age and tumor stage was developed. Tumor mutation burden (TMB), immune profile, and drug sensitivity in HCC were also analyzed. Furthermore, we employed RT-PCR to confirm the expression levels of the genes related to TMGs in HepG2 cell lines.

RESULTS: A prognostic model comprising 3 core genes was constructed, with high-risk individuals showing significantly lower overall survival (OS). The association between elevated TMB and diminished survival in high-risk patients was uncovered through TMB analysis. Immune profiling indicated notable disparities in immune infiltration among these groups, with high-risk patients displaying elevated Tumor Immune Dysfunction and Exclusion (TIDE) scores, suggesting potential immune evasion.

CONCLUSION: In short, our prognosis model based on TMGs effectively categorized HCC patients using risk scores, enabling dependable prognostic forecasts and identification of potential therapeutic targets for personalized treatment in HCC management. Future studies should explore integrating this model into clinical practice to improve patient outcomes.},
}

@article {pmid40022541,
year = {2025},
author = {Aviv, A and Verhulst, S},
title = {Telomeres in Space.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70030},
doi = {10.1111/acel.70030},
pmid = {40022541},
issn = {1474-9726},
support = {1U24AG066528/NH/NIH HHS/United States ; R01ES035760/NH/NIH HHS/United States ; U01AG066529/NH/NIH HHS/United States ; #262700//Research Council of Norway/ ; },
abstract = {Recent studies have reported that the spaceflight environment lengthens leukocyte telomeres. We propose that this baffling finding reflects changes in the composition of leukocyte subsets rather than an actual increase in telomere length within individual leukocytes. Since leukocyte telomere length is associated with aging-related diseases and longevity in humans, it is crucial to understand the underlying factors driving telomere length changes in space.},
}

@article {pmid40016654,
year = {2025},
author = {Kang, K and Nie, H and Kuang, W and Li, X and Zhou, Y},
title = {A novel telomere-associated genes signature for the prediction of prognosis and treatment responsiveness of hepatocellular carcinoma.},
journal = {Biological procedures online},
volume = {27},
number = {1},
pages = {8},
pmid = {40016654},
issn = {1480-9222},
support = {1053320221933//the Graduate Student Innovation Fund of Central South University/ ; 82203353//National Natural Science Foundation of China/ ; 2022M723565//Fellowship of China Postdoctoral Science Foundation/ ; 2022JJ40851//Natural Science Foundation of Hunan Province for Youth Foundation/ ; 2021Q16//Youth Research Foundation of Xiangya Hospital, Central South University/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, characterized by its high malignancy and poor prognosis. Telomeres, crucial components of eukaryotic chromosomes, have been increasingly recognized for their involvement in tumorigenesis, development, and impact on the prognosis of cancer patients. However, the precise role of telomere-associated genes in HCC remains incompletely elucidated.

METHODS: The Cancer Genome Atlas (TCGA) database was utilized to download data from 374 HCC and 50 normal liver tissue samples. Differential genes were screened and intersected with 2093 telomere-related genes (TRGs) in GeneCards, resulting in the identification of 704 TRGs exhibiting survival differences. Through univariate Cox regression analysis, multivariate Cox regression analysis, and LASSO regression, a prognostic model consisting of 18 TRGs for HCC risk assessment was developed. The single-cell and spatial transcriptomics were utilized to analyze the expression and distribution of 18 TRGs in HCC. Subsequently, Mendelian randomization (MR) analysis confirmed a causal relationship between ASF1A and alcoholic HCC among the identified 18 TRGs. The expression and functional significance of ASF1A in HCC cell lines were investigated through colony formation assays, Transwell migration assays, and wound healing experiments.

RESULTS: We developed a prognostic risk model for HCC incorporating 18 TRGs. Kaplan-Meier analysis demonstrated that the overall survival (OS) rate of the high-risk group was significantly inferior to that of the low-risk group. Cox regression analysis identified age (HR = 1.017, 95% CI: 1.002-1.032, P = 0.03), stage (HR = 1.389, 95% CI: 1.111-1.737, P = 0.004), and risk score (HR = 5.097, 95% CI: 3.273-7.936, P < 0.001) as three independent risk factors for HCC patients. The five-year receiver operating characteristic curve (ROC) and multivariate Cox regression analysis further validated the accuracy of our model. Time-dependent ROC results revealed that the 1-year, 3-year, and 5-year AUC values were AUC = 0.801, AUC = 0.734, and AUC = 0.690, respectively. The expression and distribution of 18 TRGs in HCC were further validated through single-cell and spatial transcriptomics data. Additionally, immune subtype analysis indicated a significantly lower proportion of C3 and C4 subtypes in the high-risk TRG group compared to the low-risk group. Meanwhile, tumor immune dysfunction and exclusion (TIDE) were significantly higher in the high-risk group than in the low-risk group. Furthermore, we observed differences in IC50 values among nine chemotherapeutic drugs across different TRG risk subtypes which partially confirmed our model's predictive efficacy for immunotherapy. Amongst these eighteen TRGs analyzed by MR analysis, ASF1A was found to be associated with alcoholic HCC pathogenesis. We further confirmed ASF1A was significant overexpression in HCC by Western blotting. We also explored it's the carcinogenic role of ASF1A in HCC via the transwell, wound healing, and clone formation experiments.

CONCLUSION: In this study, we developed a novel prognostic model comprising 18 TRGs for HCC, which exhibited remarkable accuracy in predicting HCC patients' prognosis. Additionally, through MR analysis, we have successfully established a causal relationship between ASF1A and alcoholic HCC for the first time, which also provided a new theoretical foundation for the management of alcoholic HCC.},
}

@article {pmid40016428,
year = {2025},
author = {Salgado, S and Abreu, PL and Moleirinho, B and Guedes, DS and Larcombe, L and Azzalin, CM},
title = {Author Correction: Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s44319-025-00408-6},
pmid = {40016428},
issn = {1469-3178},
}

@article {pmid40016269,
year = {2025},
author = {Zhang, K and Guo, S and Yang, S and Zhou, W and Wu, J and Zhang, X and Shi, Q and Deng, L},
title = {A telomere-to-telomere genome assembly of the protandrous hermaphrodite blackhead seabream, Acanthopagrus schlegelii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {350},
pmid = {40016269},
issn = {2052-4463},
mesh = {Animals ; *Sea Bream/genetics ; *Genome ; *Telomere/genetics ; Male ; Female ; },
abstract = {A remarkable life cycle of the protandrous blackhead seabream (Acanthopagrus schlegelii), initiating as a male during the first two years and then naturally transforming to a female since the third year, makes this fish a valuable model for studying molecular mechanisms of sex change. Here, we constructed a gap-free telomere-to-telomere (T2T) genome assembly for a male blackhead seabream, by integration of PacBio HiFi, Ultra-long ONT and Hi-C sequencing techniques. With 97.87% of the entire sequences anchored into 24 chromosomes, this haplotypic genome assembly spans 714.98 Mb. In terms of correctness (quality value QV: 52.95) and completeness (BUSCO score: 99.9%), this chromosome-scale assembly is indeed of high quality. It has been annotated with 24,581 protein-coding genes, and predicted with low percentage (30.95%) of repetitive sequences. As the first reference T2T-level genome assembly of various protandrous fishes, it provides a valuable genetic resource for expansion of fish genomics database. It will also allow for in-depth genomic comparisons among diverse hermaphrodite vertebrates, as well as offer fundamental genome data to support extensive research on blackhead seabream.},
}

Animals
*Sea Bream/genetics
*Genome
*Telomere/genetics
Male
Female

@article {pmid40015989,
year = {2025},
author = {Martin, A and Schabort, J and Bartke-Croughan, R and Tran, S and Preetham, A and Lu, R and Ho, R and Gao, J and Jenkins, S and Boyle, J and Ghanim, GE and Jagota, M and Song, YS and Li, H and Hockemeyer, D},
title = {Active telomere elongation by a subclass of cancer-associated POT1 mutations.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352492.124},
pmid = {40015989},
issn = {1549-5477},
abstract = {Mutations in the shelterin protein POT1 are associated with diverse cancers and thought to drive carcinogenesis by impairing POT1's suppression of aberrant telomere elongation. To classify clinical variants of uncertain significance (VUSs) and identify cancer-driving loss-of-function mutations, we developed a locally haploid human stem cell system to evaluate >1900 POT1 mutations, including >600 VUSs. Unexpectedly, many validated familial cancer-associated POT1 (caPOT1) mutations are haplosufficient for cellular viability, indicating that some pathogenic alleles do not act through a loss-of-function mechanism. Instead, POT1's DNA damage response suppression and telomere length control are genetically separable. ATR inhibition enables isolation of frameshift mutants, demonstrating that the only essential function of POT1 is to repress ATR. Furthermore, comparison of caPOT1 and frameshift alleles reveals a class of caPOT1 mutations that elongate telomeres more rapidly than full loss-of-function alleles. This telomere length-promoting activity is independent from POT1's role in overhang sequestration and fill-in synthesis.},
}

@article {pmid40011224,
year = {2025},
author = {Yi, J and Jiang, C and Xia, L},
title = {Mediated roles of oxidative stress and kidney function to leukocyte telomere length and prognosis in chronic kidney disease.},
journal = {Renal failure},
volume = {47},
number = {1},
pages = {2464828},
pmid = {40011224},
issn = {1525-6049},
mesh = {Humans ; *Oxidative Stress ; Male ; Female ; Middle Aged ; *Renal Insufficiency, Chronic/physiopathology/mortality ; *Leukocytes/metabolism ; Prognosis ; Aged ; *Glomerular Filtration Rate ; *Telomere ; *Nutrition Surveys ; Cardiovascular Diseases ; Neoplasms/mortality/genetics ; Risk Factors ; Adult ; Proportional Hazards Models ; Hypertension ; },
abstract = {BACKGROUND: Few studies have focused on the correlation between leukocyte telomere length (LTL) and cancer-related mortality or identified potential factors that mediate the relationship between LTL and mortality among chronic kidney disease (CKD) patients. Our study aimed to explore the associations between LTL and all-cause and cause-specific mortality and to identify the underlying mediators.

METHODS: CKD patients were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cox regression analysis and restricted cubic spline analysis were used to explore the associations between LTL and all-cause or specific-cause mortality and their nonlinear connections. Stratified analyses were executed to assess the relationships among the different subgroups. The latent mediated factors were confirmed using mediation analysis. Sensitivity analyses were used to evaluate the robustness of our findings.

RESULTS: Longer LTL associated with the lower risk of all-cause mortality, cardiovascular disease (CVD) and cancer-related mortality, and U-shaped relationships were detected. Patients younger than 65 years with greater LTL or who had hypertension had better prognoses. Age and history of hypertension were associated with LTL and overall mortality. In addition, estimated glomerular filtration rate (eGFR), albumin, and total bilirubin mediated the association, and the proportions of indirect effects were 7.81%, 3.77%, and 2.50%, respectively. Six sensitivity analyses confirmed the robustness of our findings.

CONCLUSIONS: This study revealed that LTL was a protective factor for survival among patients with CKD and emphasized the mediating roles of oxidative stress and kidney function.},
}

Humans
*Oxidative Stress
Male
Female
Middle Aged
*Renal Insufficiency, Chronic/physiopathology/mortality
*Leukocytes/metabolism
Prognosis
Aged
*Glomerular Filtration Rate
*Telomere
*Nutrition Surveys
Cardiovascular Diseases
Neoplasms/mortality/genetics
Risk Factors
Adult
Proportional Hazards Models
Hypertension

@article {pmid40011083,
year = {2025},
author = {Zeng, Y and Yuan, X and Zi, J and Hu, Y and Wang, X and Cheng, G and Xiong, J},
title = {Telomere length mediates the causal effects of excess adiposity on cardiovascular risk: A two-step Mendelian randomization study.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {103904},
doi = {10.1016/j.numecd.2025.103904},
pmid = {40011083},
issn = {1590-3729},
abstract = {BACKGROUND AND AIMS: Excess adiposity correlate to cardiovascular diseases, inflammation, and telomere shortening, while the latter two are associated with cardiovascular risks. Whether inflammation and telomere length mediate the excess adiposity-cardiovascular relationship is unclear.

METHODS AND RESULTS: We performed a two-step Mendelian randomization analysis utilizing data from the latest genome-wide association studies: body mass index (BMI, n = 681,275), waist-to-hip ratio (WHR, n = 697,734) and BMI adjusted WHR (WHRadjBMI, n = 694,649), telomere length (n = 472,174), C-reactive protein (n = 204,402), interleukin-6 and interleukin-1 receptor antagonist (n = 21,758), tumor necrosis factor-α (n = 3454), hypertension (n = 463,010), coronary artery disease (n = 547,261), heart failure (n = 977,323), stroke (n = 446,696), ischemic stroke (n = 440,328), intracerebral hemorrhage (n = 343,663), aortic aneurysm (n = 356,934), transient ischemic attack (n = 360,692), peripheral vascular disease (n = 463,010), systolic and diastolic blood pressure changes (n = 757,601). We observed casual effects of excess adiposity on eight cardiovascular diseases, hypertension and blood pressure changes. Telomere length is causally associated with hypertension, blood pressure, coronary artery disease, aortic aneurysm, and intracerebral hemorrhage, mediates BMI's effect on coronary artery disease (2.41 %) and aortic aneurysm (4.97 %), and plays a suppressive role between WHR and systolic blood pressure changes (2.39 %).

CONCLUSION: Telomere length mediates the causal effects of excess adiposity on the risks of coronary artery disease, aortic aneurysm, and systolic blood pressure changes.},
}

@article {pmid40008862,
year = {2025},
author = {Wąsowicz, W and Janasik, B and Reszka, E and Kasperczyk, E and Chrzanowski, J and Fendler, W},
title = {Metals (Cr, Mn, Co, Ni) concentration in the blood plasma and urine od Polish welders and telomere length as an potential indicator of toxicity of metals welding fumes exposure.},
journal = {International journal of occupational medicine and environmental health},
volume = {},
number = {},
pages = {},
doi = {10.13075/ijomeh.1896.02493},
pmid = {40008862},
issn = {1896-494X},
abstract = {OBJECTIVES: The study investigated the concentrations of metals (chromium [Cr], manganese [Mn], cobalt [Co], nickel [Ni]) in the blood plasma and urine of Polish welders exposed to these elements contained in welding dust/fumes based on the results of biological monitoring, analyze the interrelationships between these elements, and attempt to correlate these data with telomere length. It is believed that telomere length can be considered a marker of exposure, including occupational. Analysis of questionnaire surveys was also taken into consideration.

MATERIAL AND METHODS: The study included 118 male welders and 51 age-matched male controls. Metals analysis in plasma and urine were determined by ICP-MS technique. Telomere length was measured in blood genomic DNA using the qRT-PCR method.

RESULTS: Welders had significantly higher plasma levels of Cr, Ni, and Mn (p < 0.0001, respectively). Total concentrations of Cr, Ni, and Mn in the urine of pre-shift subjects were significantly higher compared to controls. Cobalt concentration in urine of exposed welders was significantly higher (p < 0.02) than in control group. Telomere length was exactly the same in the welder group compared to the control (mean ± standard deviation 0.99±0.41 vs. 0.99±0.52, respectively). Plasma and urine metal concentrations and telomere length were also studied in groups of welders in relation to personal protection equipment. Differences were found in plasma and urine metal concentrations according to the aspirators used. Statistically significant linear correlations were found between plasma and urine concentrations of the determined elements both before and after the work shift.

CONCLUSIONS: The findings suggest a positive relationship between Ni and Mn (end-shift) concentrations and telomere length, the effect which remained statistically significant even after adjusting for age and metabolic status. This indicates a complex interplay between metal exposure and biological aging markers. However, the relationship between exposure to welding fumes and changes in telomere length in welders requires further in-depth research. Int J Occup Med Environ Health. 2025;38(1).},
}

@article {pmid40004056,
year = {2025},
author = {Yan, B and Suen, MC and Xu, N and Lu, C and Liu, C and Zhu, G},
title = {G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041591},
pmid = {40004056},
issn = {1422-0067},
support = {32071188//National Scientific Foundation of China/ ; 16101120, 161011121, AoE/M-403-16, AoE/M-401/20//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; BGF.2023.019//Hong Kong University of Science and Technology, China/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation, China/ ; 32301012//Young Scientists Fund of the National Natural Science Foundation of China/ ; },
mesh = {*G-Quadruplexes ; Humans ; *Telomere/genetics ; *C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics/pathology ; },
abstract = {G-quadruplexes (G4s) are unique nucleic acid structures composed of guanine-rich (G-rich) sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS/FTD.},
}

*G-Quadruplexes
Humans
*Telomere/genetics
*C9orf72 Protein/genetics
*DNA Repeat Expansion/genetics
*Amyotrophic Lateral Sclerosis/genetics
Frontotemporal Dementia/genetics/pathology

@article {pmid40004050,
year = {2025},
author = {Anatskaya, OV and Ponomartsev, SV and Elmuratov, AU and Vinogradov, AE},
title = {Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in Adult Rat Heart.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041584},
pmid = {40004050},
issn = {1422-0067},
support = {Agreement No. 075-15-2021-1075//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Animals ; Rats ; *Cardiomyopathies/genetics/metabolism/pathology/etiology ; *Transcriptome ; *Myocytes, Cardiac/metabolism/pathology ; *Animals, Newborn ; Telomere/genetics/metabolism ; Oxidative Stress/genetics ; Cellular Senescence/genetics ; Gene Expression Profiling ; DNA Damage ; Male ; Lactose/metabolism ; },
abstract = {Cardiovascular diseases (CVD) are the primary cause of mortality globally. A significant aspect of CVD involves their association with aging and susceptibility to neonatal programming. These factors suggest that adverse conditions during neonatal development can disrupt cardiomyocyte differentiation, thereby leading to heart dysfunction. This study focuses on the long-term effects of inflammatory and oxidative stress due to neonatal lactose intolerance (NLI) on cardiomyocyte transcriptome and phenotype. Our recent bioinformatic study focused on toggle genes indicated that NLI correlates with the switch off of some genes in thyroid hormone, calcium, and antioxidant signaling pathways, alongside the switch-on/off genes involved in DNA damage response and inflammation. In the presented study, we evaluated cardiomyocyte ploidy in different regions of the left ventricle (LV), complemented by a transcriptomic analysis of genes with quantitative (gradual) difference in expression. Cytophotometric and morphologic analyses of LV cardiomyocytes identified hyperpolyploidy and bridges between nuclei suggesting telomere fusion. Transcriptomic profiling highlighted telomere damage, aging, and chromatin decompaction, along with the suppression of pathways governing muscle contraction and energy metabolism. Echocardiography revealed statistically significant LV dilation and a decrease in ejection fraction. The estimation of survival rates indicated that NLI shortened the median lifespan by approximately 18% (p < 0.0001) compared with the control. Altogether, these findings suggest that NLI may increase susceptibility to cardiovascular diseases by accelerating aging due to oxidative stress and increased telomere DNA damage, leading to hyperpolyploidization and reduced cardiac contractile function. Collectively, our data emphasize the importance of the early identification and management of neonatal inflammatory and metabolic stressors, such as NLI, to mitigate long-term cardiovascular risks.},
}

Animals
Rats
*Cardiomyopathies/genetics/metabolism/pathology/etiology
*Transcriptome
*Myocytes, Cardiac/metabolism/pathology
*Animals, Newborn
Telomere/genetics/metabolism
Oxidative Stress/genetics
Cellular Senescence/genetics
Gene Expression Profiling
DNA Damage
Male
Lactose/metabolism

@article {pmid40003720,
year = {2025},
author = {Chaithanya, V and Kumar, J and Vajravelu Leela, K and Baig, HA and Soliman, M and Alenezy, A and Shalaby, NM},
title = {Multistrain Probiotics and Telomere Length in Type 2 Diabetes: A 24-Week Randomized Controlled Trial.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/life15020311},
pmid = {40003720},
issn = {2075-1729},
support = {SRMIST/R/AR(A)/SERI2023/174/21-3866.//SRM Institute of Science and Technology/ ; },
abstract = {BACKGROUND: This 24-week randomized controlled trial aimed to evaluate the impact of multistrain probiotic supplementation on telomere length in patients with type 2 diabetes (T2DM). The study also assessed secondary outcomes including high-sensitivity C-reactive protein (hs-CRP) and glycated hemoglobin (HbA1c).

METHODS: A total of 124 participants with T2DM were randomly assigned to either a probiotic group (n = 62) or a placebo group (n = 62). Participants in the probiotic group consumed a supplement containing fourteen live microbial strains, including Lactobacillus plantarum, L. fermentum, L. acidophilus, L. casei, L. rhamnosus, L. reuteri, L. salivarius, L. paracasei, L. gasseri, Bifidobacterium bifidum, B. lactis, B. breve, Streptococcus thermophilus, and Saccharomyces boulardii, with each strain providing 2.148 billion CFUs per capsule, totaling 30 billion CFUs. The placebo group received vitamin B12 capsules without probiotics. The primary outcome was telomere length, and secondary outcomes included hs-CRP and HbA1c levels. Data were analyzed using intention-to-treat (ITT) and per-protocol (PP) methods.

RESULTS: The probiotic group exhibited a statistically significant decrease in telomere shortening compared to the placebo group (p < 0.001). The hs-CRP levels decreased more significantly in the probiotic group (p < 0.001), suggesting potential anti-inflammatory effects. The HbA1c levels improved in the probiotic group, with a reduction of 0.44% (p = 0.004). An age-stratified analysis revealed more substantial improvements in the 30-49 years cohort, which showed greater reductions in telomere shortening, inflammatory markers, and metabolic indicators compared to the 50-69 years group.

CONCLUSIONS: Multistrain probiotic supplementation shows potential benefits in reducing telomere shortening and improving glycemic control. However, further long-term studies are needed to understand the underlying mechanisms and therapeutic implications of probiotics in T2DM.

TRIAL REGISTRATION: This trial was registered at the Clinical Trials Registry-India (CTRI/2023/07/055647).},
}

@article {pmid40002919,
year = {2025},
author = {Rajkumar, RP},
title = {Telomere Dynamics in Post-Traumatic Stress Disorder: A Critical Synthesis.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020507},
pmid = {40002919},
issn = {2227-9059},
abstract = {Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world's population. There is some evidence that PTSD is associated with accelerated cellular aging, leading to an increased risk of medical and neurodegenerative comorbidities. Alterations in telomere length (TL) and telomerase enzyme activity have been proposed as biomarkers of this process. This hypothesis was seemingly confirmed in preliminary research, but more recent studies have yielded mixed results. The current narrative review was conducted to provide a critical synthesis of existing research on telomere length and telomerase in PTSD. Data from 26 clinical studies suggest that TL in PTSD is highly variable and may be influenced by methodological, demographic, trauma-related, and psychosocial factors. There is no evidence for altered telomerase activity in PTSD. In contrast, animal research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL is not, by itself, a reliable biomarker of cellular aging in PTSD. Other markers of cellular senescence, such as epigenetic changes, may prove to be more specific in measuring this process in patients with PTSD.},
}

@article {pmid40002695,
year = {2025},
author = {Lee, J and Choi, E and Kim, H and Kim, YJ and Kim, SH},
title = {NELL2-PAX7 Transcriptional Cascade Suggests Activation Mechanism for RAD52-Dependent Alternative Lengthening of Telomeres During Malignant Transformation of Malignant Peripheral Nerve Sheath Tumors: Elongation of Telomeres and Poor Survival.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020281},
pmid = {40002695},
issn = {2227-9059},
support = {2017M3A9A7050614//National Research Foundation of Korea/ ; 2017R1D1A1B03031717//National Research Foundation of Korea/ ; 6-2016-0101//Yonsei University College of Medicine/ ; 2019-32-0024//Yonsei University College of Medicine/ ; },
abstract = {Background: In eukaryotes with a double-stranded linear DNA genome, the loss of terminal DNA during replication is inevitable due to an end-replication problem; here, telomeres serve as a buffer against DNA loss. Thus, the activation of the telomere maintenance mechanism (TMM) is a prerequisite for malignant transformation. Methods: We compared neurofibroma (NF, benign) and malignant peripheral nerve sheath tumors (MPNSTs) occurring in the same patient with type 1 neurofibromatosis, where each NF-MPNST pair shared the same genetic background and differentiation lineage; this minimizes the genetic bias and contrasts only those changes that are related to malignant transformation. A total of 20 NF-MPNST pairs from 20 NF1 patients were analyzed. Whole-transcriptome sequencing (WTS) was conducted to profile the transcriptional relationship, and whole-genome sequencing (WGS) was performed to measure the telomere length. Results: We identified 22 differentially expressed genes (DEGs) during the malignant transformation of MPNSTs. Among them, NELL2 activated PAX7, which sequentially activated RAD52, the recombinase of RAD52-dependent alternative lengthening of telomeres (ALT). RAD52 elongated MPNSTs-telomeres (p = 0.017). Otherwise, neither NELL2 nor PAX7 affected telomere length (p = 0.647 and p = 0.354, respectively). RAD52 increased MPNSTs-telomeres length, independently of NELL2 and PAX7 in multiple analyses (p = 0.021). The group with increased telomere length during the malignant transformation showed inferior overall survival (OS) (HR = 3.809, p = 0.038) to the group without increased telomere length. Accordingly, the group with increased PAX7 showed inferior OS (HR = 4.896, p = 0.046) and metastasis-free survival (MFS) (HR = 9.129, p = 0.007) in comparison to the group without increased PAX7; the group with increased RAD52 showed inferior MFS (HR = 8.669, p = 0.011) in comparison to the group without increased RAD52. Conclusions: We suggest that the NELL2-PAX7 transcriptional cascade activates RAD52-dependent ALT to increase telomere length during the malignant transformation of MPNSTs, resulting in a poor prognosis.},
}

@article {pmid39999893,
year = {2025},
author = {Burraco, P and Metcalfe, NB and Monaghan, P},
title = {Telomere dynamics in maturing frogs vary among organs.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240626},
doi = {10.1098/rsbl.2024.0626},
pmid = {39999893},
issn = {1744-957X},
support = {//ERC/ ; //Ramón y Cajal Fellowship/ ; //Spanish Ministry of Science and Innovation/ ; //European Union/ ; },
mesh = {Animals ; *Telomere ; *Xenopus laevis/genetics/physiology ; Male ; Female ; Liver/metabolism ; Temperature ; Aging ; Larva/growth & development/physiology/genetics ; Telomere Shortening ; Muscle, Skeletal/growth & development/metabolism/physiology ; Myocardium/metabolism ; Metamorphosis, Biological ; },
abstract = {It is important to know whether organs age at the same rate and are equally affected by developmental conditions as this provides insights into causes of ageing. However, data on organ-specific telomere dynamics remain scant. In a previous study of the early life of the amphibian Xenopus laevis, we detected changes in telomere lengths in gut cells, while liver, heart and muscle telomeres were unchanged; larval rearing temperature had minimal effects. Here, we extend that study to examine telomere dynamics in the same four organs and larval temperature treatments from 70-day post-metamorphic juvenile Xenopus through to sexually mature (2-year-old) adults. Telomeres shortened from juvenile to adult in the gut, heart and hindlimb muscle. In contrast, liver telomere lengths did not change with age but were shorter if the early life temperature was warm. Organ telomere lengths were influenced by sex only in adults. Warmer larval temperatures were also associated with longer gut telomeres in juveniles. Hence, pre-metamorphic conditions can influence post-metamorphic telomere dynamics, and telomere loss between juvenile and adult life stages occurs in different organs from those affected earlier in life. These findings indicate the existence of organ-dependent ageing rates across lifetimes, potentially related to developmental and environmental history.},
}

Animals
*Telomere
*Xenopus laevis/genetics/physiology
Male
Female
Liver/metabolism
Temperature
Aging
Larva/growth & development/physiology/genetics
Telomere Shortening
Muscle, Skeletal/growth & development/metabolism/physiology
Myocardium/metabolism
Metamorphosis, Biological

@article {pmid39998303,
year = {2025},
author = {Myers, KC and Davies, SM and Lutzko, C and Wahle, R and Grier, DD and Aubert, G and Norris, K and Baird, DM and Koga, M and Ko, AC and Amano, T and Amano, M and Yu, H and Ko, MSH},
title = {Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.},
journal = {NEJM evidence},
volume = {4},
number = {3},
pages = {EVIDoa2400252},
doi = {10.1056/EVIDoa2400252},
pmid = {39998303},
issn = {2766-5526},
mesh = {Humans ; Male ; Female ; *Hematopoietic Stem Cells/metabolism ; *Telomere/metabolism ; Adult ; Dyskeratosis Congenita/genetics/pathology/therapy ; Transcription Factors/genetics/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cell Mobilization ; Adolescent ; Young Adult ; Antigens, CD34/metabolism ; },
abstract = {BACKGROUND: Extremely short telomeres in patients with dyskeratosis congenita and related telomere biology disorders (TBDs) lead to premature cellular senescence and bone marrow failure. Zinc finger and SCAN domain-containing 4 (ZSCAN4) elongates telomeres by recombination.

METHODS: We report a clinical study in which EXG34217, the term given for autologous CD34+ hematopoietic stem cells from patients with TBD exposed to a temperature-sensitive Sendai virus vector encoding human ZSCAN4 at 33°C for 24 hours, was infused into patients without preconditioning.

RESULTS: Four patients were enrolled; two experienced successful CD34+ mobilization during the second mobilization attempt and underwent apheresis and EXG34217 infusion, with follow-up of 5 and 24 months (both ongoing). We observed telomere elongation (1.06- to 1.34-fold) in CD34+ cells ex vivo. In one patient, the treatment was associated with a change in the mean absolute neutrophil count (ANC) from 1.78×10[3] to 3.18×10[3] cells/μl; the lymphocyte subpopulation telomere length changed from 3.6 to 6.7 kb (50th percentile for age). In the other patient, the treatment was associated with a change in the lowest ANC from 0.6×10[3]/μl to 1.2×10[3]/μl; this has occurred in 5 months without the patient receiving prior intermittent low-dose granulocyte-colony-stimulating factor injections. During mobilization, all patients experienced mild to moderate bone pain or pain after line replacement, and one patient had a blood infection associated with fever and hypoxemia. After EXG34217 infusion, no acute safety issues were noted; in one patient mild to moderate long-term cardiac and pulmonary adverse events were noted; these were similar to symptoms of the patient's underlying conditions.

CONCLUSIONS: Although definitive conclusions cannot be drawn from the two EXG34217-treated patients, these results warrant further investigation of CD34+ cells exposed to ZSCAN4 for treating TBDs. (Funded by Elixirgen Therapeutics; ClinicalTrials.gov number, NCT04211714.).},
}

Humans
Male
Female
*Hematopoietic Stem Cells/metabolism
*Telomere/metabolism
Adult
Dyskeratosis Congenita/genetics/pathology/therapy
Transcription Factors/genetics/metabolism
Hematopoietic Stem Cell Transplantation/methods
Hematopoietic Stem Cell Mobilization
Adolescent
Young Adult
Antigens, CD34/metabolism

@article {pmid39992010,
year = {2025},
author = {},
title = {Expression of Concern: Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1},
doi = {10.1080/10985549.2025.2462481},
pmid = {39992010},
issn = {1098-5549},
}

@article {pmid39990381,
year = {2025},
author = {Quintanilla, I and Azeroglu, B and Sagar, MAK and Stracker, TH and Lazzerini Denchi, E and Pegoraro, G},
title = {Optical Pooled Screening for the Discovery of Regulators of the Alternative Lengthening of Telomeres Pathway.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.15.638448},
pmid = {39990381},
issn = {2692-8205},
abstract = {Telomere elongation is essential for the proliferation of cancer cells. Telomere length control is achieved by either the activation of the telomerase enzyme or the recombination-based Alternative Lengthening of Telomeres (ALT) pathway. ALT is active in about 10-15% of human cancers, but its molecular underpinnings remain poorly understood, preventing the discovery of potential novel therapeutic targets. Pooled CRISPR-based functional genomic screens enable the unbiased discovery of molecular factors involved in cancer biology. Recently, Optical Pooled Screens (OPS) have significantly extended the capabilities of pooled functional genomics screens to enable sensitive imaging-based readouts at the single cell level and large scale. To gain a better understanding of the ALT pathway, we developed a novel OPS assay that employs telomeric native DNA FISH (nFISH) as an optical quantitative readout to measure ALT activity. The assay uses standard OPS protocols for library preparation and sequencing. As a critical element, an optimized nFISH protocol is performed before in situ sequencing to maximize the assay performance. We show that the modified nFISH protocol faithfully detects changes in ALT activity upon CRISPR knock-out (KO) of the FANCM and BLM genes which were previously implicated in ALT. Overall, the OPS-nFISH assay is a reliable method that can provide deep insights into the ALT pathway in a high-throughput format.},
}

@article {pmid39986429,
year = {2025},
author = {Erickson, PA and Chang, VC and He, S and Dagnall, C and Teshome, K and Machiela, MJ and Barry, KH and Pereira, EFR and Gadalla, SM and Parks, CG and Berndt, SI and Beane Freeman, LE and Andreotti, G and Hofmann, JN},
title = {Occupational Pesticide Use and Relative Leukocyte Telomere Length in the Biomarkers of Exposure and Effect in Agriculture Study.},
journal = {Environmental research},
volume = {},
number = {},
pages = {121174},
doi = {10.1016/j.envres.2025.121174},
pmid = {39986429},
issn = {1096-0953},
abstract = {Previous epidemiological studies have reported increased risks of certain cancers in relation to pesticide exposures. Although the biologic mechanisms underlying these associations are not well understood, altered telomere length has been hypothesized to play a role. We examined associations between occupational use of specific pesticides and leukocyte telomere length in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiological investigation of pesticide applicators in Iowa and North Carolina. Relative telomere length (RTL) was measured using quantitative polymerase chain reaction in leukocytes from 1,539 male pesticide applicators ≥50 years of age. We evaluated lifetime use of 47 pesticides in terms of self-reported ever use and intensity-weighted lifetime days (IWLDs), a metric integrating lifetime days of use and other factors influencing exposure. Multivariable linear regression was used to estimate percent difference in geometric mean RTL in relation to ever (vs. never) use, IWLDs of use, and timing of use [recent (last 12 months) and former vs. never use]. Mean RTL was significantly longer among ever users of the insecticides lindane (percent difference=2.20%, 95%CI: 0.45%, 3.99%) and aldicarb (percent difference=3.27%, 95%CI: 0.23%, 6.40%). Longer RTL was also associated with increasing IWLDs of lindane (highest quartile vs. never use: percent difference=4.51%, 95%CI: -0.22%, 9.46%; p-trend=0.048) and the insecticide diazinon (4.77%, 95%CI: 0.17%, 9.58%; p-trend=0.055), and with recent use of the insecticide dichlorvos (vs. never use: 8.15%, 95%CI: 1.31%, 15.46%). Increasing IWLDs of the insecticide heptachlor and the herbicide 2,4,5-TP and recent use of the herbicide metolachlor were significantly associated with shorter RTL. Our findings provide novel evidence suggesting that use of certain pesticides is associated with altered leukocyte telomere length. Notably, diazinon and lindane have previously been associated with increased risks of lung and lymphoid malignancies, respectively, and longer leukocyte telomere length has been implicated in the development of these cancers.},
}

@article {pmid39983997,
year = {2025},
author = {Page, J and Stephens, C and Richard, M and Lyons, E and Baumler, E and Verklan, MT and Lorenzo, E},
title = {The relationship between physical activity and telomere length in women: A systematic review.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112042},
doi = {10.1016/j.mad.2025.112042},
pmid = {39983997},
issn = {1872-6216},
abstract = {Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A narrative synthesis of study findings indicated PA did not have a significant relationship with TL in women. However, a possible positive relationship was noted between specific types of PA and TL, specific to combined aerobic and strength-training PA and high intensity interval training interventions. The impact of PA on TL appeared to be age-dependent as well, showing significant positive relationships between PA and TL in early and later adulthood but not in middle adulthood. Findings related to race or ethnicity were inconclusive due to limited analyses from the included studies. The studies varied greatly by PA type, intensity, duration, and frequency, which, along with the reliance on self-reported PA measures in the observational studies, impacted the ability to draw firm conclusions. This review underscores the necessity for future research in large cohort studies using objectively measured PA interventions to further clarify the complex associations between PA and TL in women.},
}

@article {pmid39983416,
year = {2025},
author = {Liu, Z and Liu, X},
title = {Prognostic model of osteosarcoma based on telomere-related genes and analysis of immune characteristics.},
journal = {International immunopharmacology},
volume = {151},
number = {},
pages = {114198},
doi = {10.1016/j.intimp.2025.114198},
pmid = {39983416},
issn = {1878-1705},
abstract = {OBJECTIVE: Osteosarcoma is a malignant tumor with significant challenges in treatment and prognosis. Telomeres play a crucial role in genetic stability and tumor development, and telomere-related genes (TRGs) have shown considerable prognostic potential in various cancers. However, the prognostic significance of TRGs in osteosarcoma and their involvement in the tumor immune microenvironment (TIME) remain poorly understood.

METHOD: This study initially identified 2086 TRGs from the TelNet database as candidate genes. Using RNA sequencing and clinical data from osteosarcoma patients available in the TARGET and GEO public databases, we developed a TRG-based prognostic scoring model through univariate, LASSO regression, and multivariate Cox regression analyses, with its predictive performance subsequently validated. Unsupervised clustering was performed on TRGs associated with prognosis. To investigate the TIME, we utilized several algorithms including ESTIMATE, CIBERSORT, xCELL, and ssGSEA to analyze the immune landscape associated with TRG patterns. Additionally, functional enrichment analysis of different subtypes was conducted using KEGG, GO, and GSVA approaches. We also performed single-cell localization and drug sensitivity analysis on the prognostic model genes. Finally, the predictive results were preliminarily validated through a series of in vitro experiments.

RESULT: Differential expression analysis revealed 841 TRGs with significant changes in osteosarcoma, where P-value < 0.05 and |logFC| ≥ 1. Based on the prognostic relevance of these TRGs, we successfully identified two subtypes with distinct clinical and immune characteristics. Immune infiltration levels between Cluster 1 and Cluster 2 were significantly different, as assessed by multiple algorithms. Furthermore, we constructed a prognostic scoring model based on TRGs, which demonstrated excellent predictive performance, with AUC values for 1-year, 3-year, and 5-year ROC curves being 92.43 %, 87.08 %, and 84.34 % in the training cohort, respectively, and 74.49 %, 87.77 %, and 94.52 % in the validation cohort, indicating good stability of the model. Notably, functional enrichment analysis highlighted a strong association between immune dysfunction and poor prognosis, while drug sensitivity analysis offered personalized chemotherapy recommendations for osteosarcoma patients with different subtypes. We observed that Fludarabine had a higher IC50 value in the high-risk group compared to the low-risk group, and it showed a strong correlation with the prognostic model genes, with all P-values less than 0.05.

CONCLUSION: This study successfully constructed a prognostic risk prediction model for osteosarcoma by systematically analyzing the expression patterns of TRGs. Fludarabine may represent a promising therapeutic option for patients with osteosarcoma.},
}

@article {pmid39982908,
year = {2025},
author = {Armendáriz-Castillo, I and García-Cárdenas, J and Espinosa, P and Hidalgo-Fernández, K and Peña-Zúñiga, L and Martínez, R and Moromenacho, J and Herrera-Yela, A and Cruz-Varela, J and Saucedo-Sariñana, A and Cerdán, ME and López-Cortés, A and Guerrero, S},
title = {Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0314012},
doi = {10.1371/journal.pone.0314012},
pmid = {39982908},
issn = {1932-6203},
mesh = {Humans ; *Telomere Homeostasis ; *Metabolic Networks and Pathways ; Neoplasms/metabolism/pathology/genetics ; Telomere/metabolism/genetics ; Purines/metabolism ; Metabolomics/methods ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation.},
}

Humans
*Telomere Homeostasis
*Metabolic Networks and Pathways
Neoplasms/metabolism/pathology/genetics
Telomere/metabolism/genetics
Purines/metabolism
Metabolomics/methods

@article {pmid39982852,
year = {2025},
author = {Jiang, D and Li, Y and Zhuge, F and Zhou, Q and Zong, W and Liu, X and Shen, X},
title = {The telomere-to-telomere genome of flowering cherry (Prunus campanulata) reveals genomic evolution of the subgenus Cerasus.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf009},
pmid = {39982852},
issn = {2047-217X},
support = {2021C02071-4//Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding/ ; 2023F1068-2//Special Support Funds of Zhejiang for Scientific Research Institutes/ ; 32101585//National Natural Science Foundation of China/ ; },
mesh = {*Genome, Plant ; *Telomere/genetics ; *Evolution, Molecular ; *Prunus/genetics ; Genomics/methods ; Phylogeny ; Molecular Sequence Annotation ; High-Throughput Nucleotide Sequencing ; },
abstract = {BACKGROUND: Prunus campanulata, a species of ornamental cherry, holds significant genetic and horticultural value. Despite the availability of various cherry genomes, a fully resolved telomere-to-telomere (T2T) assembly for this species has been lacking. Recent advancements in long-read sequencing technologies have made it possible to generate gap-free genome assemblies, providing comprehensive insights into genomic structures that were previously inaccessible.

FINDINGS: We present the first T2T genome assembly for P. campanulata "Lianmeiren" (v2.0), achieved through the integration of PacBio HiFi, ultra-long Oxford Nanopore Technologies, Illumina, and Hi-C sequencing. The assembly resulted in a highly contiguous genome with a total size of 266.23 Mb and a contig N50 of 31.6 Mb. The genome exhibits remarkable completeness (98.9% BUSCO) and high accuracy (quality value of 48.75). Additionally, 13 telomeres and putative centromere regions were successfully identified across the 8 pseudochromosomes. Comparative analysis with the previous v1.0 assembly revealed 336,943 single nucleotide polymorphisms, 107,521 indels, and 1,413 structural variations, along with the annotation of 1,402 new genes.

CONCLUSIONS: This T2T genome assembly of P. campanulata "Lianmeiren" provides a critical reference for understanding the genetic architecture of the species. It enhances our ability to study structural variations, gene function, and evolutionary biology within the Prunus genus.},
}

*Genome, Plant
*Telomere/genetics
*Evolution, Molecular
*Prunus/genetics
Genomics/methods
Phylogeny
Molecular Sequence Annotation
High-Throughput Nucleotide Sequencing

@article {pmid39981889,
year = {2025},
author = {Andreikos, D and Spandidos, DA and Georgakopoulou, VE},
title = {Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).},
journal = {International journal of oncology},
volume = {66},
number = {3},
pages = {},
doi = {10.3892/ijo.2025.5729},
pmid = {39981889},
issn = {1791-2423},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; *Telomere/genetics/metabolism ; *Mesothelioma, Malignant/genetics/pathology/drug therapy ; Mesothelioma/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Prognosis ; Polymorphism, Single Nucleotide ; Mutation ; Promoter Regions, Genetic ; },
abstract = {Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.},
}

Humans
*Telomerase/genetics/metabolism
*Biomarkers, Tumor/genetics/metabolism
*Telomere/genetics/metabolism
*Mesothelioma, Malignant/genetics/pathology/drug therapy
Mesothelioma/genetics/pathology
Lung Neoplasms/genetics/pathology
Prognosis
Polymorphism, Single Nucleotide
Mutation
Promoter Regions, Genetic

@article {pmid39980969,
year = {2024},
author = {Li, S and Zhang, L and Zhang, H},
title = {A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1532610},
pmid = {39980969},
issn = {1663-9812},
abstract = {OBJECTIVE: Osteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.

METHODS: The data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.

RESULTS: Based on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.

CONCLUSION: A telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.},
}

@article {pmid39979386,
year = {2025},
author = {Oraon, PK and Ambreen, H and Yadav, P and Ramarao, S and Goel, S},
title = {A chromosome-scale reference assembly of Vigna radiata enables delineation of centromeres and telomeres.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {305},
pmid = {39979386},
issn = {2052-4463},
support = {IOE/FRP/LS/2020/27//University of Delhi (Delhi University)/ ; BT/190/NE/TBP/2011//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; BT/PR24637/NER/95/787/2017//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; 09/0045(1617)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; 09/0045(1624)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; },
mesh = {*Centromere/genetics ; *Vigna/genetics ; *Telomere/genetics ; *Genome, Plant ; *Chromosomes, Plant/genetics ; },
abstract = {Vigna radiata (L.) R. Wilczek var. radiata (mungbean) is a pulse crop important for both the global protein security and sustainable crop production. Here, to facilitate genomics-assisted breeding programs in mungbean, we present a high-quality reference genome originating from the crop's centre of origin, India. In this study, we present a significantly continuous genome assembly of V. radiata Indian cultivar, achieved through a combination of long-read PacBio HiFi sequencing and Hi-C sequencing. The total assembled genome size is ~596 Mb equating to ~98% of the predicted genome size complemented by a contig N50 value of 10.35 Mb and a BUSCO score of 98.5%. Around 502 Mb of the assembled genome is anchored on 11 pseudochromosomes conforming to the chromosome count in the crop with distinctly identified telomeres and centromeres. We predicted a total of 43,147 gene models of which 39,144 protein coding genes were functionally annotated. The present assembly was able to resolve several gaps in the genome and provides a high-quality genomic resource for accelerating mungbean breeding programs.},
}

*Centromere/genetics
*Vigna/genetics
*Telomere/genetics
*Genome, Plant
*Chromosomes, Plant/genetics

@article {pmid39978211,
year = {2025},
author = {Brown, RA and Koss, KJ},
title = {The role of optimism, connectedness, and neighborhood collective efficacy as moderators of harsh parenting on telomere length.},
journal = {Psychoneuroendocrinology},
volume = {174},
number = {},
pages = {107373},
doi = {10.1016/j.psyneuen.2025.107373},
pmid = {39978211},
issn = {1873-3360},
abstract = {Research to date has examined telomere length in relation to adverse childhood events but few studies have examined whether protective factors act as a buffer to offset this effect. Further, research is lacking examining whether protective factors vary among minoritized youth. Data were from the Future Families and Child Wellbeing Study, a stratified, multistage sample of 4898 children born in large U.S. cities between 1998 and 2000. Births to unmarried mothers were oversampled by a 3-1 ratio, which resulted in the inclusion of a multi-ethnic and economically diverse sample (48 % Black; 27 % Hispanic; 21 % White; 4 % other racial and ethnic minorities). The current study examined optimism, social connectedness, and neighborhood collective efficacy at age 15 as potential protective factors against the effects of harsh parenting on telomere length in adolescence (analytic N = 1168 youth). This study examines cumulative exposure to harsh parenting across childhood (ages 3, 5, and 9 years). Results from analyses stratified by race/ethnicity show optimism, connectedness, and neighborhood collective efficacy serve as protective factors; however, unique protective factors emerged among different racial and ethnic youth suggesting the need to examine context-specific protective factors. Implications of these findings provide evidence for considering intersectionality in terms of protective factors for biomarkers among minoritized youth.},
}

@article {pmid39977333,
year = {2025},
author = {},
title = {Correction for Qian et al., Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2501913122},
doi = {10.1073/pnas.2501913122},
pmid = {39977333},
issn = {1091-6490},
}

@article {pmid39975089,
year = {2025},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.28.635226},
pmid = {39975089},
issn = {2692-8205},
abstract = {Telomere length is inherited directly as a DNA sequence and as a classic quantitative trait controlled by many genes across the genome. Here, we show that neither paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the Alternative Lengthening of Telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.},
}

@article {pmid39975053,
year = {2025},
author = {Sanford, SL and Badstübner, M and Gerber, M and Mannherz, W and Lampl, N and Dannenberg, R and Hinchie, A and Schaich, MA and Myong, S and Hedglin, M and Agarwal, S and Alder, J and Stone, MD and Opresko, PL},
title = {6-thio-2'-deoxyguanosine inhibits telomere elongation by inducing a non-productive stalled telomerase complex.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.05.636339},
pmid = {39975053},
issn = {2692-8205},
abstract = {Most cancers upregulate the telomere lengthening enzyme telomerase for unlimited cell division. The therapeutic nucleoside 6-thio-2'-deoxyguanosine (6-thio-dG) inhibits telomere maintenance in telomerase- expressing cancer cells and tumors by an unknown mechanism. Here, we demonstrate that telomerase insertion of 6-thio-dGTP prevents synthesis of additional telomeric repeats but does not disrupt telomerase binding to telomeres. Specifically, 6-thio-dG inhibits telomere extension after telomerase translocates along its product DNA to reposition the template, thereby inducing a non-productive complex rather than enzyme dissociation upon movement. We provide direct evidence that 6-thio-dG treatment inhibits telomere synthesis by telomerase in cancer cells. Furthermore, telomerase-expressing cancer cells harboring critically short telomeres are more sensitive to 6-thio-dG and show a greater induction of telomere losses, compared to cancer cells with long telomere reserves. Collectively, our studies reveal the molecular mechanism of 6-thio-dG inhibition of telomere maintenance in cancer cells is by producing a bound non-productive telomerase complex after 6-thio-dGTP insertion.},
}

@article {pmid39974130,
year = {2025},
author = {Toor, AA and Horton, M and Khalid, H and Krieger, E and Lai, TP and Spellman, SR and Levine, JE and Saber, W and Aviv, A and Stewart, V and Gadalla, SM},
title = {Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.20.24319630},
pmid = {39974130},
abstract = {BACKGROUND: T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different T cell clones will display variable TL; these differences across the population are not represented when examining average TL. This study aims to develop a method that integrates the entire spectrum of TL observed within a sample to better understand the influence on clinical outcomes following HCT.

METHODS: To better reflect the entire span of TL , we used data generated using the TeLSA PCR technique that provided discrete measurments of individual telomeres for each DNA sample for 72 stem cell transplant (SCT) donor-recipient pairs. Donor and recipient TeSLA TL measurements was performed on samples taken before and 90 days post HCT, respectively. Set correspondence mathematical techniques and area under the curve (AUC) calculations were used to measured donor-recipient TL differences (delta-TL) incorporating the full distribution of measured TL from each sample.

RESULTS: Telomere band lengths ranged from 350 basepairs (BP) to 16.7 kilobases with a logarithmically declining distribution in all samples when arrayed in a descending order. Set correspondence methods yielded TL averages which were highly correlated with AUC calculations (r >0.9, p<0.001 for all) The AUC delta-TL method predicted patient overall survival (P-log rank <0.0001). HCT recipients with intermediate degrees of telomere attrition (25 [th] -75 [th] percentile) post-HCT experienced the best outcomes (2 years overall survival; OS=92%), whilst donors with the least (<25 [th] percentile; 2 years OS=33%; adjusted HR vs. intermediate shortening=9.3, p=0.001) and the greatest (>75 [th] percentile; 2 years OS=59%; adjusted HR=6.0, p=0.01) shortening had worse outcomes. By contrast, using the traditional method based on donor-recipient difference in TeSLA mean telomere length did not demonstrate survival association in this small sample set (p log-rank=0.95).

CONCLUSION: The findings described herein suggest that the degree of donor telomere attrition may reflect T cell proliferation and alloreactivity following transplant. Accounting for the entire span of telomere lengths, could better identify post-transplant risk groups.},
}

@article {pmid39972993,
year = {2025},
author = {Jin, T and Yang, R and Cheng, Y and Cao, Z and He, Z and Guo, S},
title = {Causality between Autism Spectrum Disorder and Telomere Length.},
journal = {Brain and behavior},
volume = {15},
number = {2},
pages = {e70362},
doi = {10.1002/brb3.70362},
pmid = {39972993},
issn = {2162-3279},
support = {2020KY443,2022KY506,2023KY044and2024KY025//the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; GZY-ZJ-KJ-23055//Zhejiang Provincial TCM Science and Technology Plan Project/ ; },
mesh = {*Autism Spectrum Disorder/genetics ; Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Telomere ; Telomere Shortening ; Causality ; },
abstract = {BACKGROUND: The association between telomere length (TL) and autism spectrum disorder (ASD) has received much attention. However, previous observational studies have yielded inconclusive evidence regarding this relationship. Our study aims to elucidate the causal relationship between TL and ASD using bidirectional Mendelian randomization (MR).

METHODS: We employed the largest genome-wide association studies (GWAS) summary statistics for TL (sample size = 472,174) and ASD (sample size = 46,351). The primary MR analysis method was the inverse-variance weighted (IVW) method, complemented by the MR-Egger method, weighted median (WM) method, and MR-PRESSO. Additionally, sensitivity analyses including Cochran's Q test, the intercept of MR-Egger regression, the global test of MR-PRESSO, and the leave-one-out analysis were conducted in our study.

RESULTS: The primary MR analysis indicated a significant association between ASD and shorter TL (IVW: OR = 0.98, 95% CI: 0.96-0.99, p = 0.03). However, no significant association was found in the reverse direction MR analysis (IVW: OR = 1.06, 95% CI: 0.94-1.23, p = 0.35). Raw and outlier-corrected MR estimates from MR-PRESSO were consistent with the IVW results. Sensitivity analyses confirmed the robustness of these findings.

CONCLUSIONS: Our study indicated that individuals with ASD have shorter TL, however, shorter TL does not appear to increase the risk of ASD.},
}

*Autism Spectrum Disorder/genetics
Humans
*Mendelian Randomization Analysis
*Genome-Wide Association Study
Telomere
Telomere Shortening
Causality

@article {pmid39971959,
year = {2025},
author = {Guerrero-López, R and Manguán-García, C and Carrascoso-Rubio, C and Lozano, ML and Toldos-Torres, M and García-Castro, L and Sánchez-Dominguez, R and Alberquilla, O and Sánchez-Pérez, I and Molina-Molina, M and Bueren, JA and Guenechea, G and Perona, R and Sastre, L},
title = {Premature ageing of lung alveoli and bone marrow cells from Terc deficient mice with different telomere lengths.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6102},
pmid = {39971959},
issn = {2045-2322},
mesh = {Animals ; *Telomerase/genetics ; Mice ; *Telomere/genetics/metabolism ; *Aging, Premature/genetics/pathology ; *Mice, Inbred C57BL ; *RNA/genetics/metabolism ; *Bone Marrow Cells/metabolism ; Pulmonary Alveoli/pathology/metabolism ; Disease Models, Animal ; Telomere Homeostasis ; Mutation ; Male ; Telomere Shortening ; },
abstract = {Telomeres are terminal protective chromosome structures. Genetic variants in genes coding for proteins required for telomere maintenance cause rare, life-threatening Telomere Biology Disorders (TBDs) such as dyskeratosis congenita, aplastic anemia or pulmonary fibrosis. The more frequently used mice strains have telomeres much longer than the human ones which question their use as in vivo models for TBDs. One mice model with shorter telomeres based on the CAST/EiJ mouse strain carrying a mutation in the Terc gene, coding for the telomerase RNA component, has been studied in comparison with C57BL/6J mice, carrying the same mutation and long telomeres. The possible alterations produced in lungs and the haematopoietic system, frequently affected in TBD patients, were determined at different ages of the mice. Homozygous mutant mice presented a very shortened life span, more notorious in the short-telomeres CAST/EiJ strain. The lungs of mutant mice presented a transitory increase in fibrosis and a significant decrease in the relative amount of the alveolar epithelial type 2 cells from six months of age. This decrease was larger in mutant homozygous animals but was also observed in heterozygous animals. On the contrary the expression of the senescence-related protein P21 increased from six months of age in mutant mice of both strains. The analysis of the haematopoietic system indicated a decrease in the number of megakaryocyte-erythroid progenitors in homozygous mutants and an increase in the clonogenic potential of bone marrow and LSK cells. Bone marrow cells from homozygous mutant animals presented decreasing in vitro expansion capacity. The alterations observed are compatible with precocious ageing of lung alveolar cells and the bone marrow cells that correlate with the alterations observed in TBD patients. The alterations seem to be more related to the genotype of the animals that to the basal telomere length of the strains although they are more pronounced in the short-telomere CAST/EiJ-derived strain than in C57BL/6J animals. Therefore, both animal models, at ages over 6-8 months, could represent valuable and convenient models for the study of TBDs and for the assay of new therapeutic products.},
}

Animals
*Telomerase/genetics
Mice
*Telomere/genetics/metabolism
*Aging, Premature/genetics/pathology
*Mice, Inbred C57BL
*RNA/genetics/metabolism
*Bone Marrow Cells/metabolism
Pulmonary Alveoli/pathology/metabolism
Disease Models, Animal
Telomere Homeostasis
Mutation
Male
Telomere Shortening