@article {pmid39846264,
year = {2025},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and González-Sarmiento, R and Navarro-López, V and Juárez-Vela, R and Pérez, J and Martín-Vallejo, J},
title = {Effect of Physical Exercise on Telomere Length: Umbrella Review and Meta-Analysis.},
journal = {JMIR aging},
volume = {8},
number = {},
pages = {e64539},
doi = {10.2196/64539},
pmid = {39846264},
issn = {2561-7605},
mesh = {Humans ; *Exercise/physiology ; Telomere/metabolism ; Telomere Homeostasis/physiology ; Persons with Disabilities/rehabilitation ; },
abstract = {BACKGROUND: Telomere length (TL) is a marker of cellular health and aging. Physical exercise has been associated with longer telomeres and, therefore, healthier aging. However, results supporting such effects vary across studies. Our aim was to synthesize existing evidence on the effect of different modalities and durations of physical exercise on TL.

OBJECTIVE: The aim of this study was to explore the needs and expectations of individuals with physical disabilities and their interventionists for the use of a virtual reality physical activity platform in a community organization.

METHODS: We performed an umbrella review and meta-analysis. Data sources included PubMed, Embase, Web of Science, Cochrane Library, and Scopus. We selected systematic reviews and meta-analyses of randomized and nonrandomized controlled clinical trials evaluating the effect of physical exercise on TL.

RESULTS: Our literature search retrieved 12 eligible systematic reviews, 5 of which included meta-analyses. We identified 22 distinct primary studies to estimate the overall effect size of physical exercise on TL. The overall effect size was 0.28 (95% CI 0.118-0.439), with a heterogeneity test value Q of 43.08 (P=.003) and I² coefficient of 51%. The number of weeks of intervention explained part of this heterogeneity (Q_B=8.25; P=.004), with higher effect sizes found in studies with an intervention of less than 30 weeks. Exercise modality explained additional heterogeneity within this subgroup (Q_B=10.28, P=.02). The effect sizes were small for aerobic exercise and endurance training, and moderate for high-intensity interval training.

CONCLUSIONS: Our umbrella review and meta-analysis detected a small-moderate positive effect of physical exercise on TL, which seems to be influenced by the duration and type of physical exercise. High quality studies looking into the impact of standardized, evidence-based physical exercise programs on TL are still warranted.},
}

Humans
*Exercise/physiology
Telomere/metabolism
Telomere Homeostasis/physiology
Persons with Disabilities/rehabilitation

@article {pmid39844515,
year = {2025},
author = {Gao, B and Zhao, J and Li, X and Zhang, J and Oliver, MJ and Zhang, D},
title = {Telomere-to-telomere genome of the desiccation-tolerant desert moss Syntrichia caninervis illuminates Copia-dominant centromeric architecture.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.14549},
pmid = {39844515},
issn = {1467-7652},
support = {32100256//National Natural Science Foundation of China/ ; },
}

@article {pmid39844366,
year = {2025},
author = {Ormerod, MBEG and Ueland, T and Aas, M and Hjell, G and Rødevand, L and Sæther, LS and Lunding, SH and Johansen, IT and Mlakar, V and Andreou, D and Ueland, T and Lagerberg, TV and Melle, I and Djurovic, S and Andreassen, OA and Steen, NE},
title = {Limited evidence of association between dysregulated immune marker levels and telomere length in severe mental disorders.},
journal = {Acta neuropsychiatrica},
volume = {37},
number = {},
pages = {e4},
doi = {10.1017/neu.2024.62},
pmid = {39844366},
issn = {1601-5215},
mesh = {Humans ; Male ; *Bipolar Disorder/genetics/immunology/blood ; Female ; *Schizophrenia/genetics/blood/immunology ; Adult ; *Biomarkers/blood ; Middle Aged ; *Telomere ; *Leukocytes/metabolism ; Telomere Shortening ; Receptors, Tumor Necrosis Factor, Type I/blood/genetics ; Case-Control Studies ; Young Adult ; },
abstract = {OBJECTIVE: Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders.

METHODS: Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays.

RESULTS: A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (β = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups.

CONCLUSION: There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.},
}

Humans
Male
*Bipolar Disorder/genetics/immunology/blood
Female
*Schizophrenia/genetics/blood/immunology
Adult
*Biomarkers/blood
Middle Aged
*Telomere
*Leukocytes/metabolism
Telomere Shortening
Receptors, Tumor Necrosis Factor, Type I/blood/genetics
Case-Control Studies
Young Adult

@article {pmid39842387,
year = {2025},
author = {Sabaie, H and Taghavi Rad, A and Shabestari, M and Seddiq, S and Saadattalab, T and Habibi, D and Saeidian, AH and Abbasi, M and Mirtavoos-Mahyari, H},
title = {Deciphering the bidirectional impact of leukocyte telomere length on multiple sclerosis progression: A Mendelian randomization study.},
journal = {Multiple sclerosis and related disorders},
volume = {94},
number = {},
pages = {106277},
doi = {10.1016/j.msard.2025.106277},
pmid = {39842387},
issn = {2211-0356},
abstract = {Observational studies have suggested a link between leukocyte telomere length (LTL) and multiple sclerosis (MS) progression, but the causal relationship remains uncertain. This study investigates the causal association between LTL and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. We analyzed genome-wide association summary statistics data from 472,174 individuals for LTL and 12,584 MS patients for disease progression. The primary method was the inverse variance weighted (IVW) approach, supported by sensitivity analyses to ensure robustness. The forward analysis revealed a significant positive causal relationship between LTL and MS progression (β = 0.107, 95 % CI = 0.006 to 0.209, P = 0.037). Conversely, the reverse analysis indicated a negative causal relationship (β = -0.010, 95 % CI = -0.020 to -0.001, P = 0.037). No heterogeneity or horizontal pleiotropy was found, and the sensitivity analyses confirmed consistent results. These findings suggest that telomere dynamics play a complex role in MS progression and highlight their potential as therapeutic targets. Further research is essential to uncover the biological mechanisms underlying the influence of telomeres on MS progression.},
}

@article {pmid39841197,
year = {2025},
author = {Masuda, Y and Sadato, D and Toya, T and Hirama, C and Shimizu, H and Najima, Y and Harada, H and Harada, Y and Doki, N},
title = {Telomere shortening in donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation: a case report.},
journal = {Annals of hematology},
volume = {},
number = {},
pages = {},
pmid = {39841197},
issn = {1432-0584},
abstract = {Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes. Donor origin of APL cells was validated by conventional karyotyping, florescence in situ hybridization, and single-nucleotide polymorphisms-based chimerism analysis. Targeted sequencing of both the donor and the recipient demonstrated newly-acquired PML::RARA fusion only in the recipient's cells after transplantation, without additional genetic abnormalities. The telomere length was measured at multiple timepoints before and after transplantation. The analysis revealed markedly shortened telomere length at APL onset, which reflect both stem cell expansion following transplantation and expansion of APL cells. Our first-ever report of telomere dynamics in DCL cases provides evidence for the involvement of telomere attrition in DCL pathogenesis.},
}

@article {pmid39837488,
year = {2025},
author = {Schiavinato, M and Ronanki, S and Estruch, IM and van den Brink, N},
title = {Immune response accelerated telomere shortening during early life stage of a passerine bird, the blue tit (Cyanistes caeruleus).},
journal = {Biology letters},
volume = {21},
number = {1},
pages = {20240618},
doi = {10.1098/rsbl.2024.0618},
pmid = {39837488},
issn = {1744-957X},
support = {//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; },
mesh = {Animals ; *Telomere Shortening ; *Poly I-C/pharmacology ; Passeriformes/immunology/physiology ; Brain/metabolism ; Lipid Peroxidation ; Leukocyte Count ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Aging ; Erythrocytes ; },
abstract = {Dealing with infections is a daily challenge for wild animals. Empirical data show an increase in reactive oxygen species (ROS) production during immune response. This could have consequences on telomere length, the end parts of linear chromosomes, commonly used as proxy for good health and ageing. Telomere length dynamics may reflect the costs associated with physiological responses. In this study, immune system of blue tit (Cyanistes caeruleus) nestlings was experimentally challenged through a polyinosinic:polycytidylic acid (poly I:C) injection, a synthetic double-stranded RNA that mimics a virus, activating the pathway of immune response triggered via the toll-like receptors 3. This path is known to form ROS downstream. Immune response was quantified by white cell counts in blood, while brain lipoperoxidation has been evaluated as an indicator of oxidative damage. Finally, individuals' telomere length shortening between days 8 and 15 after hatching was measured in erythrocytes. Challenged nestlings showed increased leukocyte number when compared with control (treated with a saline solution), lower brain lipid peroxidation (likely as a result of a compensatory mechanism after oxidative stress burst) and accelerated telomere shortening. These findings support the 'ageing cost of infections pathway' hypothesis, which supposes a role for infections in quick biological ageing.},
}

Animals
*Telomere Shortening
*Poly I-C/pharmacology
Passeriformes/immunology/physiology
Brain/metabolism
Lipid Peroxidation
Leukocyte Count
Oxidative Stress
Reactive Oxygen Species/metabolism
Aging
Erythrocytes

@article {pmid39835465,
year = {2025},
author = {Paldino, G and Tedeschi, V and Proganò, V and Salvati, E and Licursi, V and Vertecchi, E and Bivolaru, AL and Molteni, E and Scrivo, R and Congia, M and Cauli, A and Caccavale, R and Paroli, M and Kunkl, M and Tuosto, L and Sorrentino, R and Fiorillo, MT},
title = {An immunosenescent CD8+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43109},
pmid = {39835465},
issn = {2326-5205},
abstract = {OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA).

METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA-seq analysis whereas telomere length and dysfunction were measured by RT-PCR and IF-fluorescence in situ hybridization (FISH), respectively.

RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared to HD and RA patients. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (TNFα), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer (NK) markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response (DDR) activation, telomere shortening and dysfunction.

CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in SpA patients that represents a possible player in disease pathogenesis.},
}

@article {pmid39834735,
year = {2024},
author = {Liu, M and Wang, C and Wei, B},
title = {Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and telomere length: the NHANES 1999-2002.},
journal = {Frontiers in cardiovascular medicine},
volume = {11},
number = {},
pages = {1407452},
doi = {10.3389/fcvm.2024.1407452},
pmid = {39834735},
issn = {2297-055X},
abstract = {BACKGROUND: The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and telomere length (TL) remains unclear. This study aims to investigate their association in a nationally representative US population.

METHODS: Data from 6,342 adults aged ≥20 were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The NHHR was calculated and categorized into tertiles. TL was measured as the telomere-to-standard reference DNA ratio. Multivariate linear regression and smooth curve fitting were employed to assess the association between NHHR and TL.

RESULTS: The study population (mean age 45.1 ± 0.4 years, 48.9% male) was stratified into NHHR tertiles. Compared with the lowest NHHR tertile, the highest NHHR tertile was associated with adverse inflammatory and cardiometabolic profiles, including elevated white blood cell counts (6.88 ± 0.07-7.54 ± 0.08 × 10[9]/L) and increased prevalence of hypertension (18.81%-25.71%) and diabetes (3.38%-7.17%). An elevated NHHR was significantly associated with a shorter TL (T/S ratio: 1.09 ± 0.02-1.03 ± 0.02; P = 0.0005). This association remained significant in partially adjusted models but was attenuated in a fully adjusted model. Significant interactions were observed for age and hypertension status.

CONCLUSION: This study revealed a linear inverse association between NHHR and TL, suggesting the utility of the NHHR as a novel biomarker for biological aging. Further prospective studies are warranted to validate these findings.},
}

@article {pmid39833200,
year = {2025},
author = {Jiménez-Martín, A and Pineda-Santaella, A and Martín-García, R and Esteban-Villafañe, R and Matarrese, A and Pinto-Cruz, J and Camacho-Cabañas, S and León-Periñán, D and Terrizzano, A and Daga, RR and Braun, S and Fernández-Álvarez, A},
title = {Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {837},
pmid = {39833200},
issn = {2041-1723},
mesh = {*Schizosaccharomyces/genetics/cytology/metabolism ; *Telomere/metabolism/genetics ; *Centromere/metabolism/genetics ; *Meiosis ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; Chromosomes, Fungal/genetics/metabolism ; },
abstract = {Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using Schizosaccharomyces pombe as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, play a key role in the initiation of telomere bouquet formation. We demonstrate that centromeres are capable to induce telomere mobilization, which is sufficient to trigger the first stages of bouquet assembly and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation and meiotic transcriptional rewiring.},
}

*Schizosaccharomyces/genetics/cytology/metabolism
*Telomere/metabolism/genetics
*Centromere/metabolism/genetics
*Meiosis
*Schizosaccharomyces pombe Proteins/metabolism/genetics
Chromosomes, Fungal/genetics/metabolism

@article {pmid39828703,
year = {2025},
author = {Zhao, Q and Yin, Z and Hou, Z},
title = {Near telomere-to-telomere genome assemblies of Silkie Gallus gallus and Mallard Anas platyrhynchos restored the structure of chromosomes and "missing" genes in birds.},
journal = {Journal of animal science and biotechnology},
volume = {16},
number = {1},
pages = {9},
pmid = {39828703},
issn = {1674-9782},
abstract = {BACKGROUND: Chickens and ducks are vital sources of animal protein for humans. Recent pangenome studies suggest that a single genome is insufficient to represent the genetic information of a species, highlighting the need for more comprehensive genomes. The bird genome has more than tens of microchromosomes, but comparative genomics, annotations, and the discovery of variations are hindered by inadequate telomere-to-telomere level assemblies. We aim to complete the chicken and duck genomes, recover missing genes, and reveal common and unique chromosomal features between birds.

RESULTS: The near telomere-to-telomere genomes of Silkie Gallus gallus and Mallard Anas platyrhynchos were successfully assembled via multiple high-coverage complementary technologies, with quality values of 36.65 and 44.17 for Silkie and Mallard, respectively; and BUSCO scores of 96.55% and 96.97% for Silkie and Mallard, respectively; the mapping rates reached over 99.52% for both assembled genomes, these evaluation results ensured high completeness and accuracy. We successfully annotated 20,253 and 19,621 protein-coding genes for Silkie and Mallard, respectively, and assembled gap-free sex chromosomes in Mallard for the first time. Comparative analysis revealed that microchromosomes differ from macrochromosomes in terms of GC content, repetitive sequence abundance, gene density, and levels of 5mC methylation. Different types of arrangements of centromeric repeat sequence centromeres exist in both Silkie and the Mallard genomes, with Mallard centromeres being invaded by CR1. The highly heterochromatic W chromosome, which serves as a refuge for ERVs, contains disproportionately long ERVs. Both Silkie and the Mallard genomes presented relatively high 5mC methylation levels on sex chromosomes and microchromosomes, and the telomeres and centromeres presented significantly higher 5mC methylation levels than the whole genome. Finally, we recovered 325 missing genes via our new genomes and annotated TNFA in Mallard for the first time, revealing conserved protein structures and tissue-specific expression.

CONCLUSIONS: The near telomere-to-telomere assemblies in Mallard and Silkie, with the first gap-free sex chromosomes in ducks, significantly enhanced our understanding of genetic structures in birds, specifically highlighting the distinctive chromosome features between the chicken and duck genomes. This foundational work also provides a series of newly identified missing genes for further investigation.},
}

@article {pmid39827100,
year = {2025},
author = {Domínguez-de-Barros, A and Pérez-Rubio, G and Fricke-Galindo, I and Ramírez-Venegas, A and Gajate-Arenas, M and Hernández-Zenteno, R and García-Carmona, S and Robles-Hernández, R and Ramírez-Díaz, ME and Cruz-Vicente, F and Martínez-Gómez, ML and Lorenzo-Morales, J and Falfán-Valencia, R and Córdoba-Lanús, E},
title = {Shorter telomere length in COPD cases secondary to biomass-burning smoke exposure.},
journal = {Respiratory research},
volume = {26},
number = {1},
pages = {23},
pmid = {39827100},
issn = {1465-993X},
support = {2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; 2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; 2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; ACIISI 2024//Agencia Canaria de Investigación, Innovación y Sociedad de la Información/ ; (CB21/13/00100)//Consorcio Centro de Investigación Biomédica (CIBER) de Enfermedades Infecciosas (CIBERINFEC) , Instituto de Salud Carlos III, 28006 Madrid, Spain/ ; (CB21/13/00100)//Consorcio Centro de Investigación Biomédica (CIBER) de Enfermedades Infecciosas (CIBERINFEC) , Instituto de Salud Carlos III, 28006 Madrid, Spain/ ; },
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/genetics/epidemiology/diagnosis ; Male ; Female ; Middle Aged ; *Smoke/adverse effects ; *Biomass ; Aged ; Telomere Shortening ; Telomere ; Adult ; Mexico/epidemiology ; Telomere Homeostasis/physiology ; },
abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and destruction of lung tissue, primarily attributed to tobacco smoking. However, other factors like biomass-burning smoke (BS) exposure are also implicated. COPD has been described as an accelerated aging disease, and telomere length is a biomarker of aging.

METHODS: This study examined telomere length in 189 Mexican individuals, from which 93 developed COPD secondary to BS exposure (BE-COPD); the rest of the participants were exposed to BS but did not develop the disease. Lung function parameters were measured by spirometry, and relative telomere length (rTL) from peripheral blood DNA was determined using multiplex qPCR.

RESULTS: Results showed rTL to inversely correlate with age (R[2]=-0.207, p = 0.006) and with the hours-a-day of BS exposure (R[2]=-0.297, p < 0.001). Within BE-COPD cases, rTL was associated with daily BS exposure, and BE-COPD individuals exhibited a reduced rTL compared to controls (1.39 ± 0.45 vs. 0.89 ± 0.50; p < 0.001). When compared by rTL length in BE-COPD cases, longer telomeres were associated with decreased COPD risk (β = 0.134, 95% CI = 0.053-0.339; p < 0.001). However, no significant relationship was found between rTL and clinical or lung function parameters in the BE-COPD group.

CONCLUSIONS: This is the first study to document that individuals with COPD secondary to biomass smoke exposure present shorter telomeres than BS-exposed subjects who did not develop the disease.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/genetics/epidemiology/diagnosis
Male
Female
Middle Aged
*Smoke/adverse effects
*Biomass
Aged
Telomere Shortening
Telomere
Adult
Mexico/epidemiology
Telomere Homeostasis/physiology

@article {pmid39826692,
year = {2025},
author = {Comstock, W and Bhattarai, S and Sanford, E and Navarro, M and Smolka, MB},
title = {Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {108194},
doi = {10.1016/j.jbc.2025.108194},
pmid = {39826692},
issn = {1083-351X},
abstract = {The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In S. cerevisiae, the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood. Here we performed an in depth phosphoproteomic screen for Tel1-dependent phosphorylation events. To achieve maximal coverage of the phosphoproteome, we developed a scaled-up approach that accommodates large amounts of protein extracts and chromatographic fractions. Compared to previous reports, we expanded the number of detected Tel1-dependent phosphorylation events by over 10-fold. Surprisingly, in addition to the identification of phosphorylation sites featuring the canonical motif for Tel1 phosphorylation (S/T-Q), the results revealed a novel motif (D/E-S/T) highly prevalent and enriched in the set of Tel1-dependent events. This motif is unique to Tel1 signaling and not shared with the Mec1 kinase, providing clues to how Tel1 plays specialized roles in DNA repair and telomere length control. Overall, these findings define a Tel1-signaling network targeting numerous proteins involved in DNA repair, chromatin regulation, and telomere maintenance that represents a framework for dissecting the molecular mechanisms of Tel1 action.},
}

@article {pmid39826712,
year = {2025},
author = {Yu, X and Zhang, H},
title = {Biomolecular Condensates in Telomere Maintenance of ALT Cancer Cells.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {168951},
doi = {10.1016/j.jmb.2025.168951},
pmid = {39826712},
issn = {1089-8638},
abstract = {Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent mechanism that utilizes homology-directed repair (HDR) to sustain telomere length in specific cancers. Biomolecular condensates, such as ALT-associated promyelocytic leukemia nuclear bodies (APBs), have emerged as critical players in the ALT pathway, supporting telomere maintenance in ALT-positive cells. These condensates bring together DNA repair proteins, telomeric repeats, and other regulatory elements. By regulating replication stress and promoting DNA synthesis, ALT condensates create an environment conducive to HDR-based telomere extension. This review explores recent advancements in ALT, focusing on understanding the role of biomolecular condensates in ALT and how they impact telomere dynamics and stability.},
}

@article {pmid39825185,
year = {2025},
author = {Cui, J and Wang, R and Gu, R and Chen, M and Wang, Z and Li, L and Hong, J and Cui, S},
title = {Telomere-to-telomere Phragmites australis reference genome assembly with a B chromosome provides insights into its evolution and polysaccharide biosynthesis.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {73},
pmid = {39825185},
issn = {2399-3642},
support = {31972934, 31170784//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Poaceae/genetics/metabolism ; *Genome, Plant ; *Evolution, Molecular ; *Polysaccharides/biosynthesis/metabolism/genetics ; *Chromosomes, Plant/genetics ; Telomere/genetics/metabolism ; Phylogeny ; Gene Duplication ; },
abstract = {Phragmites australis is a globally distributed grass species (Poaceae) recognized for its vast biomass and exceptional environmental adaptability, making it an ideal model for studying wetland ecosystems and plant stress resilience. However, genomic resources for this species have been limited. In this study, we assembled a chromosome-level reference genome of P. australis containing one B chromosome. An explosion of LTR-RTs, centered on the Copia family, occurred during the late Pleistocene, driving the expansion of P. australis genome size and subgenomic differentiation. Comparative genomic analysis showed that P. australis underwent two whole gene duplication events, was segregated from Cleistogenes songorica at 34.6 Mya, and that 41.26% of the gene families underwent expansion. Based on multi-tissue transcriptomic data, we identified structural genes in the biosynthetic pathway of pharmacologically active Phragmitis rhizoma polysaccharides with essential roles in rhizome development. This study deepens our understanding of Arundinoideae evolution, genome dynamics, and the genetic basis of key traits, providing essential data and a genetic foundation for wetland restoration, bioenergy development, and plant stress.},
}

*Poaceae/genetics/metabolism
*Genome, Plant
*Evolution, Molecular
*Polysaccharides/biosynthesis/metabolism/genetics
*Chromosomes, Plant/genetics
Telomere/genetics/metabolism
Phylogeny
Gene Duplication

@article {pmid39817136,
year = {2025},
author = {Wang, Q and Li, QR and Xu, L and Yuan, ZC and Liu, X and Tang, MJ and Luo, M and Zhong, XW and Ma, Q and Guo, XL},
title = {BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {1},
pages = {99376},
pmid = {39817136},
issn = {1948-5204},
abstract = {BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.

AIM: To investigate the efficacy and underlying mechanisms of BIBR1532, a telomerase inhibitor, in ESCC.

METHODS: KYSE150 and KYSE410 cells were cultured and exposed to various concentrations of BIBR1532. Cell viability was assessed at 48 hours and 72 hours to determine the IC50 values. The effects of BIBR1532 on ESCC cell proliferation, migration, and cellular senescence were evaluated using the cell counting kit-8 assay, plate colony formation assay, scratch assay, transwell assay, and β-galactosidase staining, respectively. Western blotting was performed to detect the expression of proteins in BIBR1532-treated ESCC cells, such as human telomerase reverse transcriptase (hTERT), key molecules involved in DNA damage response (DDR) or cellular senescence, as well as telomere-binding proteins. Additionally, a tumor-bearing nude mouse model was established to evaluate the anti-cancer effect of BIBR1532 in vivo.

RESULTS: The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53 μM and 39.59 μM, respectively. These values decreased to 37.22 μM and 22.71 μM, respectively, following a longer exposure of 72 hours. BIBR1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells, including decreased hTERT expression, inhibition of proliferation and metastasis, and induction of cellular senescence. Mechanistically, BIBR1532 upregulated the expression of the DDR protein, γ-H2AX, and activated the ataxia telangiectasia and Rad3-related protein (ATR)/ check point kinase 1 (CHK-1) and ataxia-telangiectasia mutated gene (ATM)/CHK2 pathways. BIBR1532 downregulated the expression of telomere-binding proteins, including telomeric-repeat binding factor 1 (TRF1), TRF2, protection of telomeres 1, and TIN2-interacting protein 1. In a nude mouse xenograft model, BIBR1532 significantly suppressed tumor growth, reduced hTERT expression, and increased γ-H2AX protein levels. Hematoxylin and eosin staining of various organs, including the heart, liver, spleen, lungs, and kidneys, revealed no apparent adverse effects.

CONCLUSION: BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins.},
}

@article {pmid39814758,
year = {2025},
author = {Krawczyk, K and Szablińska-Piernik, J and Paukszto, Ł and Maździarz, M and Sulima, P and Przyborowski, JA and Szczecińska, M and Sawicki, J},
title = {Chromosome-scale telomere to telomere genome assembly of common crystalwort (Riccia sorocarpa Bisch.).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {77},
pmid = {39814758},
issn = {2052-4463},
support = {2020/39/B/NZ8/02504//Narodowe Centrum Nauki (National Science Centre)/ ; },
mesh = {*Telomere/genetics ; *Genome, Plant ; Chromosomes, Plant ; Hepatophyta/genetics ; DNA Methylation ; },
abstract = {Riccia sorocarpa Bisch., commonly known as common crystalwort, is a plant belonging to the Marchantiales order with a cosmopolitan distribution among a wide range of habitats: fields, gardens, waste ground, on paths, cliff tops, and thin soil over rocks or by water bodies. However, research into the genetic aspects of this species is limited. In this study, the chromosome-scale telomere-to-telomere genome of R. sorocarpa was assembled exclusively by Oxford Nanopore long-read sequencing and Pore-C technology. A high-quality chromosomal-scale assembly was obtained with a final genome size of 376.690 Mbp, contig N50 of 49.132 Mbp and 97.02% of the assembled contigs associated with the eight chromosomes. Genome assembly completeness was confirmed by BUSCO analysis accounting 91.8%. Among 27,626 total genes, 23,562 (85.29%) were functionally annotated. Moreover, collinearity of Marchantiales was analyzed as well as gene family evolution and DNA methylation profile. The availability of this genome, which is the second telomere-to-telomere liverwort assembly, opens up new avenues for in-depth analysis of R. sorocarpa genetic diversity and genomic characteristics.},
}

*Telomere/genetics
*Genome, Plant
Chromosomes, Plant
Hepatophyta/genetics
DNA Methylation

@article {pmid39813504,
year = {2025},
author = {Castro, MCS and Costa, LC and Salum, KCR and Castro, HA and Ribeiro, PC and Costa, W and Nani, ASF and Kohlrausch, FB},
title = {Silica-exposed patients with silicosis show shorter telomeres than do unexposed individuals: a pilot study in a population in southeastern Brazil.},
journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia},
volume = {50},
number = {6},
pages = {e20240318},
doi = {10.36416/1806-3756/e20240318},
pmid = {39813504},
issn = {1806-3756},
mesh = {Humans ; *Silicosis/genetics ; Male ; Brazil/epidemiology ; Pilot Projects ; *Occupational Exposure/adverse effects ; *Silicon Dioxide/adverse effects/toxicity ; Middle Aged ; Case-Control Studies ; *Telomere Shortening/drug effects ; Adult ; Oxidative Stress ; Telomere/drug effects ; Severity of Illness Index ; Smoking/adverse effects ; },
abstract = {OBJECTIVE: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes. We aimed to determine whether telomere length (TL) correlates with silicosis or severity of silicosis in silica-exposed workers in Brazil.

METHODS: We included 200 men in southeastern Brazil: 100 with silicosis and 100 who had not been exposed to silica. We extracted DNA from buccal cells and assessed TL by multiplex quantitative polymerase chain reaction.

RESULTS: The median TL was significantly shorter in the patients with silicosis than in the unexposed controls (p < 0.0001), although it did not differ between the patients with simple silicosis and those with complicated silicosis (p = 0.961). We also found that, in patients with silicosis, TL was influenced by smoking (p = 0.034) and by a history of personal protective equipment use in the workplace (p = 0.002).

CONCLUSIONS: Silica exposure appears to have an impact on TL, which was found to be shorter in patients with silicosis than in unexposed controls. Further studies are needed in order to confirm the impact that oxidative stress caused by silica inhalation has on telomeres.},
}

Humans
*Silicosis/genetics
Male
Brazil/epidemiology
Pilot Projects
*Occupational Exposure/adverse effects
*Silicon Dioxide/adverse effects/toxicity
Middle Aged
Case-Control Studies
*Telomere Shortening/drug effects
Adult
Oxidative Stress
Telomere/drug effects
Severity of Illness Index
Smoking/adverse effects

@article {pmid39809206,
year = {2024},
author = {Lyu, TT and Wang, JY and Tan, JS and Yang, YM and Wang, YM and Zhao, J and Qing, P and Wu, LM and Wang, XJ},
title = {Causal associations between telomere length and pulmonary arterial hypertension: A two-sample Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {47},
pages = {e40407},
doi = {10.1097/MD.0000000000040407},
pmid = {39809206},
issn = {1536-5964},
support = {2022†GSPâ€GGâ€26//the Highâ€Level Hospital Clinical Research Funding/ ; 2023-GSP-GG-41//the Highâ€Level Hospital Clinical Research Funding/ ; 2023-GSP-GG-24//the Highâ€Level Hospital Clinical Research Funding/ ; NCRC2020015//National Clinical Medical Research Center for Cardiovascular Diseases/ ; 7222142//the Beijing Natural Science Foundation/ ; 82170408//National Natural Science Foundation/ ; 82070353//National Natural Science Foundation/ ; 81800300//National Natural Science Foundation/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *Polymorphism, Single Nucleotide ; *Genome-Wide Association Study ; *Telomere/genetics ; Pulmonary Arterial Hypertension/genetics ; Hypertension, Pulmonary/genetics ; Telomere Homeostasis/genetics ; },
abstract = {Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by elevated pulmonary artery pressure, leading to right heart failure, and mortality. The role of telomere length, a marker of biological aging, in PAH remains unclear. We utilized summary-level data from genome-wide association studies for various measures of telomere length and PAH. Single nucleotide polymorphisms associated with telomere length at a genome-wide significance level were used as instrumental variables. The inverse variance weighted method was the primary analysis, with sensitivity analyses including the weighted median and Mendelian randomization-Egger regression. The odds ratios and 95% confidence intervals (CI) were calculated to estimate the causal effect of telomere length on PAH risk. The Mendelian randomization analyses revealed no significant causal association between overall telomere length and PAH (odds ratios per standard deviation increase = 1.229, 95% CI: 0.469-3.222, P = .676). Similar null findings were observed for granulocyte, lymphocyte, naive T-cell, memory T-cell, B-cell, and natural killer-cell telomere lengths. Sensitivity analyses confirmed the robustness of the results, with no evidence of horizontal pleiotropy or significant influence of individual single nucleotide polymorphisms on the overall estimates. This Mendelian randomization study didn't support a causal association between telomere length and PAH.},
}

*Mendelian Randomization Analysis
Humans
*Polymorphism, Single Nucleotide
*Genome-Wide Association Study
*Telomere/genetics
Pulmonary Arterial Hypertension/genetics
Hypertension, Pulmonary/genetics
Telomere Homeostasis/genetics

@article {pmid39805504,
year = {2025},
author = {Boccardi, V and Marano, L},
title = {The telomere connection between aging and cancer: The burden of replication stress and dysfunction.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112026},
doi = {10.1016/j.mad.2025.112026},
pmid = {39805504},
issn = {1872-6216},
abstract = {Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and diminished repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.},
}

@article {pmid39803571,
year = {2024},
author = {Khandagale, P and Sun, Y and Saha, S and Saha, LK and Pommier, Y},
title = {Topoisomerase 3α (TOP3A) Dependent Alternative Lengthening of Telomeres (ALT).},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.18.624152},
pmid = {39803571},
issn = {2692-8205},
abstract = {Alternative Lengthening of Telomeres (ALT) is a homologous recombination-dependent telomere elongation mechanism utilized by at least 10-15% of all cancers. Here we identified that the DNA topoisomerase, TOP3A is enriched at the telomeres of ALT cells but not at the telomeres of telomerase-positive (Tel) cancer cells. We demonstrate that TOP3A stabilizes the shelterin protein TERF2 in ALT cancer cell lines but not in Tel cells and that long non-coding telomere transcribed RNA (TERRA) enrichment at telomeres depends upon TOP3A. TOP3A also promotes the generation of single-stranded telomeric C-strand (ssTeloC) DNA, which is a recently discovered marker for ALT. Additionally, we found that inducing TOP3A-DNA-protein crosslinks in ALT cells suppresses TERRA enrichment as well as destabilizes TERF2. Taken together these observations uncover the unexplored functions of TOP3A at ALT telomeres and suggest the potential of developing an ALT-specific cancer therapeutic strategy targeting TOP3A.},
}

@article {pmid39803201,
year = {2025},
author = {Krams, R and Cīrule, D and Munkevics, M and Popovs, S and Jõers, P and Contreras Garduño, J and Krams, IA and Krama, T},
title = {Great Tit (Parus major) Nestlings Have Longer Telomeres in Old-Growth Forests Than in Young Forests.},
journal = {Ecology and evolution},
volume = {15},
number = {1},
pages = {e70823},
pmid = {39803201},
issn = {2045-7758},
abstract = {Modification and deterioration of old-growth forests by industrial forestry have seriously threatened species diversity worldwide. The loss of natural habitats increases the concentration of circulating glucocorticoids and incurs chronic stress in animals, influencing the immune system, growth, survival, and lifespan of animals inhabiting such areas. In this study, we tested whether great tit (Parus major) nestlings grown in old-growth unmanaged coniferous forests have longer telomeres than great tit nestlings developing in young managed coniferous forests. This study showed that the patches of young managed coniferous forests had lower larval biomass than old-growth forests. Since insect larvae are the preferred food for great tit nestlings, the shortage of food may divert energy resources away from growth, which can show up as physiological stress, often raising the heterophil/lymphocyte (H/L) ratio. The H/L ratio revealed a significant difference in stress levels, being the highest in great tit nestlings developing in young-managed pine forests. We also found that the development of great tit nestlings in young managed forests had significantly shorter telomeres than in old-growth forests. Although nestling survival did not differ between the habitats, nestlings growing up in old-growth forests had greater telomere lengths, which can positively affect their lifespan. Our results suggest that the forest habitats affected by industrial forestry may represent ecological traps, as the development of young birds in deteriorated environments can affect the age structure of populations.},
}

@article {pmid39800618,
year = {2024},
author = {Su, Y and Yin, L and Zhao, Y and Zhao, Y and Zhang, W and Ke, Y and Wang, M and He, X and Liu, M and Liu, G and Qin, P and Hu, F and Zhang, M and Hu, D},
title = {The association of telomere length and coronary heart disease: A systematic review and dose-response meta-analysis.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {103830},
doi = {10.1016/j.numecd.2024.103830},
pmid = {39800618},
issn = {1590-3729},
abstract = {AIMS: The association of telomere length (TL) and coronary heart disease (CHD) is still debated, and there is a lack of dose-response meta-analyses on this issue. The aim is therefore to integrate existing evidence on the association between TL and CHD risk and explore the dose-response relationship between them.

DATA SYNTHESIS: PubMed, EMBASE, and Web of Science were searched for relevant studies up to September 2024. Meta-analysis was performed using a random-effects model, with data presented as RRs and 95 % CIs. Restricted cubic splines were used to assess linear and nonlinear associations. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Fourteen articles (8 prospective cohort studies, 2 case-cohort studies, 2 case-control studies, and 2 cross-sectional studies) were finally included in the meta-analysis, with a total sample size of 199,562 participants and 25,752 cases. For CHD, the total RR for the highest TL group compared to the lowest TL group was 0.69 (95 % CI: 0.61, 0.78, I[2] = 64.5 %). For every 1 kilobase pair (kbp) increase in TL, the CHD risk decreased by 23 % (RR = 0.77, 95 % CI: 0.69, 0.87, I[2] = 89.0 %). The nonlinearity test indicated a linear association between TL and CHD risk (Pnon-linearity = 0.930). Sensitivity analyses indicated that the results were robust.

CONCLUSIONS: The meta-analysis showed a linear relationship between TL and CHD. People with low TL may be more likely to develop CHD than those with high TL. The association between the two did not change in a wide range of populations.},
}

@article {pmid39797337,
year = {2025},
author = {Sánchez-Badajos, S and Ortega-Vázquez, A and López-López, M and Monroy-Jaramillo, N},
title = {Valproic Acid and Lamotrigine Differentially Modulate the Telomere Length in Epilepsy Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {1},
pages = {},
pmid = {39797337},
issn = {2077-0383},
support = {34605034//Universidad Autónoma Metropolitana Unidad Xochimilco/ ; },
abstract = {Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, and the choice varies according to seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging; however, few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring the telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: We used real-time quantitative PCR (QPCR) in epilepsy patients compared to matched healthy controls (CTs) and assessed the association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CTs. Patients were grouped based on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG + VPA). Multivariable logistic regression was applied to analyze the obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than in CTs (1.50 ± 0.35 vs. 1.68 ± 0.34; p < 0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and patients on an LTG + VPA combined scheme (1.77 ± 0.24; 1.50 ± 0.32; 1.36 ± 0.37, respectively; p < 0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD responses in epilepsy patients.},
}

@article {pmid39796144,
year = {2024},
author = {Sawicki, K and Matysiak-Kucharek, M and Gorczyca-Siudak, D and Kruszewski, M and Kurzepa, J and Kapka-Skrzypczak, L and Dziemidok, P},
title = {Leukocyte Telomere Length as a Marker of Chronic Complications in Type 2 Diabetes Patients: A Risk Assessment Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
doi = {10.3390/ijms26010290},
pmid = {39796144},
issn = {1422-0067},
support = {No. 21060//Instytut Medycyny Wsi im. Witolda Chodźki/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/blood ; Male ; Female ; *Leukocytes/metabolism ; Middle Aged ; *Biomarkers/blood ; *Telomere/metabolism/genetics ; Aged ; Risk Assessment/methods ; Telomere Shortening ; Diabetic Nephropathies/blood/etiology/genetics ; Diabetic Retinopathy/etiology/blood ; Telomere Homeostasis ; },
abstract = {Telomere shortening has been linked to type 2 diabetes (T2D) and its complications. This study aims to determine whether leukocyte telomere length (LTL) could be a useful marker in predicting the onset of complications in patients suffering from T2D. Enrolled study subjects were 147 T2D patients. LTL was measured using a quantitative PCR method. Key subject's demographics and other clinical characteristics were also included. T2D patients with the shortest LTL had higher TC and non-HDL levels, compared to subjects with the longest LTL (p = 0.013). Also, T2D patients suffering from diabetic nephropathy showed significant differences in LDL levels (p = 0.023). While in the group of T2D patients with diabetic retinopathy, significant differences were observed for parameters, such as duration of diabetes (p = 0.043), HbA1c (p = 0.041), TC (p = 0.003), LDL (p = 0.015), Non-HDL (p = 0.004) and TG (p = 0.045). Logistic regression analysis confirmed a significant risk of association of TC and Non-HDL levels with LTL in the 3rd tertile LTL for the crude model adjusted for sex and age, with respective odds ratios of 0.71 (95% CI 0.56-0.91) and 0.73 (95% CI 0.58-0.91). No significant associations were found between LTL in T2D patients and the prevalence of common T2D complications. Nevertheless, a significant association was demonstrated between LTL and some markers of dyslipidemia, including in T2D patients with either diabetic nephropathy or retinopathy. Therefore, analysis of LTL in T2D patients' leukocytes demonstrates a promising potential as a marker in predicting the onset of complications in T2D. This could also help in establishing an effective treatment strategy or even prevent and delay the onset of these severe complications.},
}

Humans
*Diabetes Mellitus, Type 2/complications/blood
Male
Female
*Leukocytes/metabolism
Middle Aged
*Biomarkers/blood
*Telomere/metabolism/genetics
Aged
Risk Assessment/methods
Telomere Shortening
Diabetic Nephropathies/blood/etiology/genetics
Diabetic Retinopathy/etiology/blood
Telomere Homeostasis

@article {pmid39795052,
year = {2025},
author = {Dewulf, M and Duchateau, L and Meesters, M and Martens, DS and Nawrot, TS and Van Eetvelde, M and Opsomer, G},
title = {Telomere Length in Neonatal Dairy Calves in Relation to Lifetime Parameters.},
journal = {Animals : an open access journal from MDPI},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/ani15010109},
pmid = {39795052},
issn = {2076-2615},
support = {1SH5N24N//Research Foundation - Flanders/ ; 12X9623N//Research Foundation - Flanders/ ; },
abstract = {Telomere length (TL) has gained attention as a biomarker for longevity and productivity in dairy cattle. This study explored the association between neonatal TL in Holstein calves and lifetime parameters (lifespan, milk production, and reproduction). Blood samples were collected from 210 calves (≤10d old) across four dairy farms in Flanders, Belgium. Telomere length was measured using qPCR and analyzed as a continuous variable and across three groups: the 10% shortest, the 10% longest, and the remaining 80%. Survival analyses showed no association between TL and lifespan (p = 0.1) or TL groups (p = 0.8). Similarly, TL showed no significant association with production traits. However, categorical analyses revealed that calves with the longest TL had lower lifetime fat (p = 0.01) and protein yields (p = 0.01) than those with the shortest TL. Reproductive analyses showed cows in the long TL group required fewer inseminations per lactation (p = 0.02) and exhibited longer calving intervals (p = 0.05). These findings suggest that while neonatal TL may not predict productive lifespan, it may provide insight into reproductive efficiency. Future studies should prioritize longitudinal assessments of TL dynamics to better understand their interactions with management practices and application in herd improvement.},
}

@article {pmid39791491,
year = {2025},
author = {Gan, D and Baylin, A and Peterson, KE and Rosero-Bixby, L and Ruiz-Narváez, EA},
title = {Social Connections, Leukocyte Telomere Length, and All-Cause Mortality in Older Adults From Costa Rica: The Costa Rican Longevity and Healthy Aging Study (CRELES).},
journal = {Journal of aging and health},
volume = {},
number = {},
pages = {8982643251313923},
doi = {10.1177/08982643251313923},
pmid = {39791491},
issn = {1552-6887},
abstract = {OBJECTIVES: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans.

METHODS: Utilizing data from the Costa Rican Longevity and Healthy Aging Study (CRELES), a prospective cohort of 2827 individuals aged 60 and above followed since 2004, we constructed a Social Network Index (SNI) based on marital status, household size, interaction with non-cohabitating adult children, and church attendance. We used linear regression to assess SNI's association with baseline LTL (N = 1113), and Cox proportional-hazard models to examine SNI's relationship with all-cause mortality (N = 2735).

RESULTS: Higher SNI levels were associated with longer telomeres and decreased all-cause mortality during follow-up. Being married and regular church attendance were associated with 23% and 24% reductions of the all-cause mortality, respectively.

DISCUSSION: These findings underscore the importance of social engagement in promoting longevity among older Costa Ricans, suggesting broader implications for aging populations globally.},
}

@article {pmid39780848,
year = {2025},
author = {Medina-Neira, D and Alvarado-Gamarra, G and Huamaní-Condori, B and Purizaca-Rosillo, N and Atamari-Anahui, N and Matos-Villena, E and Garces-Ghilardi, R and Estupiñan-Vigil, M},
title = {Hemophagocytic lymphohistiocytosis as the initial manifestation of bone marrow failure in a child with a TERC variant telomere biology disorder.},
journal = {Therapeutic advances in rare disease},
volume = {6},
number = {},
pages = {26330040241311621},
pmid = {39780848},
issn = {2633-0040},
abstract = {Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome, rarely associated with bone marrow failure (BMF). Telomere biology disorders (TBD) are caused by inherited defects in telomerase processes and can have heterogeneous presentations including idiopathic pulmonary fibrosis, cirrhosis, and BMF. We report a case of a 10-year-old male from Lima, Peru, who presented with HLH as the initial manifestation of a TBD. He experienced fever, gastrointestinal symptoms, and mucocutaneous involvement. Initial laboratory analyses revealed pancytopenia and elevated inflammatory markers. Despite symptomatic and antibiotic treatment, his clinical condition persisted leading to a suspicion of Kawasaki disease and, subsequently, HLH. Immunomodulatory treatment was initiated with a good clinical response. Bone marrow aspiration revealed severe hypocellular bone marrow and cytophagocytosis. Genetic studies identified a pathogenic variant in the TERC gene (n.110_113del), which was also found in the patient's mother and brother. HLH as the initial manifestation of BMF is rare. This case highlights the importance of considering TBD in children with BMF of unclear etiology and the value of genetic testing in such cases.},
}

@article {pmid39779954,
year = {2025},
author = {Luo, LY and Wu, H and Zhao, LM and Zhang, YH and Huang, JH and Liu, QY and Wang, HT and Mo, DX and EEr, HH and Zhang, LQ and Chen, HL and Jia, SG and Wang, WM and Li, MH},
title = {Telomere-to-telomere sheep genome assembly identifies variants associated with wool fineness.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39779954},
issn = {1546-1718},
support = {32320103006//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Ongoing efforts to improve sheep reference genome assemblies still leave many gaps and incomplete regions, resulting in a few common failures and errors in genomic studies. Here, we report a 2.85-Gb gap-free telomere-to-telomere genome of a ram (T2T-sheep1.0), including all autosomes and the X and Y chromosomes. This genome adds 220.05 Mb of previously unresolved regions and 754 new genes to the most updated reference assembly ARS-UI_Ramb_v3.0; it contains four types of repeat units (SatI, SatII, SatIII and CenY) in centromeric regions. T2T-sheep1.0 has a base accuracy of more than 99.999%, corrects several structural errors in previous reference assemblies and improves structural variant detection in repetitive sequences. Alignment of whole-genome short-read sequences of global domestic and wild sheep against T2T-sheep1.0 identifies 2,664,979 new single-nucleotide polymorphisms in previously unresolved regions, which improves the population genetic analyses and detection of selective signals for domestication (for example, ABCC4) and wool fineness (for example, FOXQ1).},
}

@article {pmid39778865,
year = {2025},
author = {Kim, J and Park, JL and Yang, JO and Kim, S and Joe, S and Park, G and Hwang, T and Cho, MJ and Lee, S and Lee, JE and Park, JH and Yeo, MK and Kim, SY},
title = {Highly accurate Korean draft genomes reveal structural variation highlighting human telomere evolution.},
journal = {Nucleic acids research},
volume = {53},
number = {1},
pages = {},
doi = {10.1093/nar/gkae1294},
pmid = {39778865},
issn = {1362-4962},
support = {2020M3E5D708517212//Ministry of Science and ICT/ ; RS-2024-00438566//Ministry of Health and Welfare/ ; P0009796//Ministry of Trade, Industry and Energy/ ; KGM5192221//KRIBB Research Initiative Program/ ; },
mesh = {Humans ; *Telomere/genetics ; *Genome, Human/genetics ; *Evolution, Molecular ; Republic of Korea ; Genomic Structural Variation ; DNA Repair/genetics ; Asian People/genetics ; Genomics/methods ; },
abstract = {Given the presence of highly repetitive genomic regions such as subtelomeric regions, understanding human genomic evolution remains challenging. Recently, long-read sequencing technology has facilitated the identification of complex genetic variants, including structural variants (SVs), at the single-nucleotide level. Here, we resolved SVs and their underlying DNA damage-repair mechanisms in subtelomeric regions, which are among the most uncharted genomic regions. We generated ∼20 × high-fidelity long-read sequencing data from three Korean individuals and their partially phased high-quality de novo genome assemblies (contig N50: 6.3-58.2 Mb). We identified 131 138 deletion and 121 461 insertion SVs, 41.6% of which were prevalent in the East Asian population. The commonality of the SVs identified among the Korean population was examined by short-read sequencing data from 103 Korean individuals, providing the first comprehensive SV set representing the population based on the long-read assemblies. Manual investigation of 19 large subtelomeric SVs (≥5 kb) and their associated repair signatures revealed the potential repair mechanisms leading to the formation of these SVs. Our study provides mechanistic insight into human telomere evolution and can facilitate our understanding of human SV formation.},
}

Humans
*Telomere/genetics
*Genome, Human/genetics
*Evolution, Molecular
Republic of Korea
Genomic Structural Variation
DNA Repair/genetics
Asian People/genetics
Genomics/methods

@article {pmid39775841,
year = {2025},
author = {Zhou, Y and Wang, C and Wang, B and Xu, D and Zhang, X and Ge, Y and Jiang, S and Tang, F and Chen, C and Li, X and Jian, J and You, Y},
title = {Telomere-to-telomere genome and resequencing of 254 individuals reveal evolution, genomic footprints in Asian icefish, Protosalanx chinensis.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giae115},
pmid = {39775841},
issn = {2047-217X},
support = {2023YFD2400900//National Key Research and Development Program of China/ ; },
mesh = {*Telomere/genetics ; *Evolution, Molecular ; *Genomics/methods ; Animals ; *Genome ; Genetic Variation ; Genetics, Population ; China ; },
abstract = {The Asian icefish, Protosalanx chinensis, has undergone extensive colonization in various waters across China for decades due to its ecological and physiological significance as well as its economic importance in the fishery resource. Here, we decoded a telomere-to-telomere (T2T) genome for P. chinensis combining PacBio HiFi long reads and ultra-long ONT (nanopore) reads and Hi-C data. The telomere was identified in both ends of the contig/chromosome. The expanded gene associated with circadian entrainment suggests that P. chinensis may exhibit a high sensitivity to photoperiod. The contracted genes' immune-related families and DNA repair associated with positive selection in P. chinensis suggested the selection pressure during adaptive evolution. The population genetic analysis reported the genetic diversity and genomic footprints in 254 individuals from 8 different locations. The natural seawater samples can be the highest diversity and different from other freshwater and introduced populations. The divergent regions' associated genes were found to be related to the osmotic pressure system, suggesting adaptations to alkalinity and salinity. Thus, the T2T genome and genetic variation can be valuable resources for genomic footprints in P. chinensis, shedding light on its evolution, comparative genomics, and the genetic differences between natural and introduced populations.},
}

*Telomere/genetics
*Evolution, Molecular
*Genomics/methods
Animals
*Genome
Genetic Variation
Genetics, Population
China

@article {pmid39772744,
year = {2025},
author = {Dubois, JC and Bonnell, E and Filion, A and Frion, J and Zimmer, S and Riaz Khan, M and Teplitz, GM and Casimir, L and Méthot, É and Marois, I and Idrissou, M and Jacques, PÉ and Wellinger, RJ and Maréchal, A},
title = {The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {2},
pages = {e2419712122},
doi = {10.1073/pnas.2419712122},
pmid = {39772744},
issn = {1091-6490},
support = {506663//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; FDN154315//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; },
mesh = {Humans ; *Telomere/metabolism ; *Telomere Homeostasis ; *DNA Replication ; Cell Line, Tumor ; DNA-Binding Proteins/metabolism/genetics ; Neoplasms/genetics/metabolism/pathology ; DNA, Single-Stranded/metabolism/genetics ; },
abstract = {To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies. ALT cells also have high telomeric replication stress (RS) enhanced by fork-stalling structures (R-loops and G4s) and altered chromatin states. In ALT cells, telomeric RS promotes telomere elongation but above a certain threshold becomes detrimental to cell survival. Manipulating RS at telomeres has thus been proposed as a therapeutic strategy against ALT cancers. Through analysis of genome-wide CRISPR fitness screens, we identified ALT-specific vulnerabilities and describe here our characterization of the roles of SUB1, a ssDNA-binding protein, in telomere stability. SUB1 depletion increases RS at ALT telomeres, profoundly impairing ALT cell growth without impacting telomerase-positive cells. During RS, SUB1 is recruited to stalled forks and ALT telomeres via its ssDNA-binding domain. This recruitment is potentiated by RPA depletion, suggesting that these factors may compete for ssDNA. The viability of ALT cells and their resilience toward RS also requires ssDNA binding by SUB1. SUB1 depletion accelerates cell death induced by FANCM depletion, triggering unsustainable levels of telomeric damage in ALT cells. Finally, combining SUB1 depletion with RS-inducing drugs rapidly induces replication catastrophe in ALT cells. Altogether, our work identifies SUB1 as an ALT susceptibility with roles in the mitigation of RS at ALT telomeres and suggests advanced therapeutic strategies for a host of still poorly managed cancers.},
}

Humans
*Telomere/metabolism
*Telomere Homeostasis
*DNA Replication
Cell Line, Tumor
DNA-Binding Proteins/metabolism/genetics
Neoplasms/genetics/metabolism/pathology
DNA, Single-Stranded/metabolism/genetics

@article {pmid39767532,
year = {2024},
author = {Han, CJ and Ning, X and Burd, CE and Tounkara, F and Kalady, MF and Noonan, AM and Von Ah, D},
title = {A Machine Learning Classification Model for Gastrointestinal Health in Cancer Survivors: Roles of Telomere Length and Social Determinants of Health.},
journal = {International journal of environmental research and public health},
volume = {21},
number = {12},
pages = {},
doi = {10.3390/ijerph21121694},
pmid = {39767532},
issn = {1660-4601},
support = {no grant number//The Ohio State University Cancer Center, ONF RE03/ ; },
mesh = {Humans ; *Machine Learning ; Male ; Middle Aged ; Female ; *Social Determinants of Health ; *Cancer Survivors/statistics & numerical data ; Aged ; Adult ; Telomere ; Gastrointestinal Diseases ; Nutrition Surveys ; Health Status ; },
abstract = {BACKGROUND: Gastrointestinal (GI) distress is prevalent and often persistent among cancer survivors, impacting their quality of life, nutrition, daily function, and mortality. GI health screening is crucial for preventing and managing this distress. However, accurate classification methods for GI health remain unexplored. We aimed to develop machine learning (ML) models to classify GI health status (better vs. worse) by incorporating biological aging and social determinants of health (SDOH) indicators in cancer survivors.

METHODS: We included 645 adult cancer survivors from the 1999-2002 NHANES survey. Using training and test datasets, we employed six ML models to classify GI health conditions (better vs. worse). These models incorporated leukocyte telomere length (TL), SDOH, and demographic/clinical data.

RESULTS: Among the ML models, the random forest (RF) performed the best, achieving a high area under the curve (AUC = 0.98) in the training dataset. The gradient boosting machine (GBM) demonstrated excellent classification performance with a high AUC (0.80) in the test dataset. TL, several socio-economic factors, cancer risk behaviors (including lifestyle choices), and inflammatory markers were associated with GI health. The most significant input features for better GI health in our ML models were longer TL and an annual household income above the poverty level, followed by routine physical activity, low white blood cell counts, and food security.

CONCLUSIONS: Our findings provide valuable insights into classifying and identifying risk factors related to GI health, including biological aging and SDOH indicators. To enhance model predictability, further longitudinal studies and external clinical validations are necessary.},
}

Humans
*Machine Learning
Male
Middle Aged
Female
*Social Determinants of Health
*Cancer Survivors/statistics & numerical data
Aged
Adult
Telomere
Gastrointestinal Diseases
Nutrition Surveys
Health Status

@article {pmid39766323,
year = {2024},
author = {Yilmaz, M and Goksen, S and Mender, I and Esendagli, G and Erdener, SE and Ahmed, A and Tenekeci, AK and Birichevskaya, LL and Gryaznov, SM and Shay, JW and Dikmen, ZG},
title = {A Phosphatidyl Conjugated Telomerase-Dependent Telomere-Targeting Nucleoside Demonstrates Colorectal Cancer Direct Killing and Immune Signaling.},
journal = {Biomolecules},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/biom14121616},
pmid = {39766323},
issn = {2218-273X},
support = {CA142543,CA070907/GF/NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Antineoplastic Agents/pharmacology/chemistry ; Cell Line, Tumor ; *Colorectal Neoplasms/drug therapy/pathology/metabolism/genetics ; Nucleosides/pharmacology/chemistry ; Signal Transduction/drug effects ; *Telomerase/antagonists & inhibitors/metabolism ; *Telomere/drug effects/metabolism ; },
abstract = {Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4[+] and CD8[+] T cells while reducing regulatory T cells, indicating immune system enhancement. Notably, diC6-THIO exhibits an improved solubility profile while maintaining comparable anticancer properties, further supporting its potential as a promising therapeutic candidate. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.},
}

Animals
Humans
Mice
Antineoplastic Agents/pharmacology/chemistry
Cell Line, Tumor
*Colorectal Neoplasms/drug therapy/pathology/metabolism/genetics
Nucleosides/pharmacology/chemistry
Signal Transduction/drug effects
*Telomerase/antagonists & inhibitors/metabolism
*Telomere/drug effects/metabolism

@article {pmid39763972,
year = {2024},
author = {Janovič, T and Perez, GI and Schmidt, JC},
title = {TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.12.23.630076},
pmid = {39763972},
issn = {2692-8205},
abstract = {The shelterin complex protects chromosome ends from the DNA damage repair machinery and regulates telomerase access to telomeres. Shelterin is composed of six proteins (TRF1, TRF2, TIN2, TPP1, POT1 and RAP1) that can assemble into various subcomplexes in vitro . However, the stoichiometry of the shelterin complex and its dynamic association with telomeres in cells is poorly defined. To quantitatively analyze the shelterin function in living cells we generated a panel of cancer cell lines expressing HaloTagged shelterin proteins from their endogenous loci. We systematically determined the total cellular abundance and telomeric copy number of each shelterin subunit, demonstrating that the shelterin proteins are present at telomeres in equal numbers. In addition, we used single-molecule live-cell imaging to analyze the dynamics of shelterin protein association with telomeres. Our results demonstrate that TRF1-TIN2-TPP1-POT1 and TRF2-RAP1 form distinct subcomplexes that occupy non-overlapping binding sites on telomeric chromatin. TRF1-TIN2-TPP1-POT1 tightly associates with chromatin, while TRF2-RAP1 binding to telomeres is more dynamic, allowing it to recruit a variety of co-factors to chromatin to protect chromosome ends from DNA repair factors. In total, our work provides critical mechanistic insight into how the shelterin proteins carry out multiple essential functions in telomere maintenance and significantly advances our understanding of macromolecular structure of telomeric chromatin.},
}

@article {pmid39762386,
year = {2025},
author = {Bi, G and Zhao, S and Yao, J and Wang, H and Zhao, M and Sun, Y and Hou, X and Haas, FB and Varshney, D and Prigge, M and Rensing, SA and Jiao, Y and Ma, Y and Yan, J and Dai, J},
title = {Author Correction: Near telomere-to-telomere genome of the model plant Physcomitrium patens.},
journal = {Nature plants},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41477-024-01903-9},
pmid = {39762386},
issn = {2055-0278},
}

@article {pmid39760184,
year = {2025},
author = {Doolittle, BR and Britt, KC and Lekwauwa, R and Sebu, J and Boateng, A},
title = {The association of telomere length and religiosity: A systematic review.},
journal = {Biodemography and social biology},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/19485565.2024.2448946},
pmid = {39760184},
issn = {1948-5573},
abstract = {OBJECTIVE: Religiosity is a complex construct comprised observance, intrinsic beliefs, meditative practice, and communal elements. Religiosity has been associated with reduced mortality and improved overall health, but understanding the underlying biological associations is evolving. As increased telomere length has been associated with increased longevity, this project presents a systematic review of studies investigating the relationship between religiosity and telomere length.

DESIGN: The study protocol was registered prior to the search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was followed. Seven databases were employed using relevant criteria: PubMed, PSYCHinfo, CINAHL, ATLA, Scopus, Sociological Abstracts, and the Cochrane Central Register of Controlled Clinical.

RESULTS: A total of 381 studies were identified and 46 studies met full screening. Eight studies met the final inclusion criteria. Of these eight studies, two showed no relationship between religiosity and telomere length, three showed a positive relationship, and three showed an equivocal or ambivalent relationship. Meta-analysis was not possible due to the heterogeneity of the studies.

CONCLUSION: Religiosity may be associated with telomere length, but results vary widely across the diverse studies included. Longitudinal studies with adequate sample size are needed to determine this association more rigorously.},
}

@article {pmid39759351,
year = {2024},
author = {Molina-Pinelo, S and Ferrer Sánchez, I and Najarro, P and Paz-Ares, L and Fernández, L and Castelló, N and Richart López, LA and Rodríguez Gambarte, JD and Sanz García, M and Salinas, A and Suárez, R and Romero-Romero, B and Martín-Juan, J and Viñuela, ME and Butler, RG and de Pedro, N},
title = {Telomere-based risk models for the early diagnosis of lung cancer.},
journal = {Heliyon},
volume = {10},
number = {24},
pages = {e41040},
pmid = {39759351},
issn = {2405-8440},
abstract = {BACKGROUND: The objective of this study was to evaluate the use of telomere length measurements as diagnostic biomarkers during early screening for lung cancer in high-risk patients.

METHODS: This was a prospective study of patients undergoing lung cancer diagnosis at two Spanish hospitals between April 2017 and January 2020. Telomeres from peripheral blood lymphocytes were analysed by Telomere Analysis Technology, which is based in high-throughput quantitative fluorescent in situ hybridization. Analytical predictive models were developed using Random Forest from the dataset of telomere-associated variables (TAV). Receiver Operating Characteristic curves were used to characterize model performance.

FINDINGS: From 233 patients undergoing lung cancer diagnosis, 106 patients aged 55-75 with lung cancer or lung cancer and COPD were selected. A control group (N = 453) included individuals of similar age with COPD or healthy. Telomere analysis showed that patients in the cancer cohort had a higher proportion of short telomeres compared to the control cohort. A TAV-based predictive model assuming a prevalence of 5 % of lung cancer among screened subjects showed an AUC of 0.98 %, a positive predictive value of 0.60 (95 % CI, 0.49-0.70) and a negative predictive value of 0.99 (95 % CI, 0.98-0.99) for prediction of lung cancer.

INTERPRETATION: The results of this study suggest that TAV analysis in peripheral lymphocytes can be considered a useful diagnostic tool during screening for lung cancer in high-risk patients. TAV-based models could improve the predictive power of current initial diagnostic pathways, but further work is needed to integrate them into routine clinical evaluation.

FUNDING: Life Length SL.},
}

@article {pmid39757226,
year = {2025},
author = {Ye, Z and Huang, Y and Chen, T and Wu, Y},
title = {Comprehensive analysis of telomere and aging-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma.},
journal = {Journal of cardiothoracic surgery},
volume = {20},
number = {1},
pages = {31},
pmid = {39757226},
issn = {1749-8090},
mesh = {Humans ; *Adenocarcinoma of Lung/genetics/immunology/drug therapy ; *Lung Neoplasms/genetics/drug therapy/immunology ; Prognosis ; *Immunotherapy/methods ; *Telomere/genetics ; Male ; Female ; Aging/genetics/immunology ; Middle Aged ; Nomograms ; Aged ; Biomarkers, Tumor/genetics ; },
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) is a high-risk malignancy. Telomeres- (TRGs) and aging-related genes (ARGs) play an important role in cancer progression and prognosis. This study aimed to develop a novel prognostic model combined TRGs and ARGs signatures to predict the prognosis of patients with LUAD.

METHODS: LUAD patient's sample data and clinical data were obtained from public databases. The prognostic model was constructed and evaluated using the least absolute shrinkage and selection operator (LASSO), multivariate Cox analysis, time-dependent receiver operating characteristic (ROC), and Kaplan-Meier (K-M) analysis. Immune cell infiltration levels were assessed using single-sample gene set enrichment analysis (ssGSEA). Antitumor drugs with significant correlations between drug sensitivity and the expression of prognostic genes were identified using the CellMiner database. The distribution and expression levels of prognostic genes in immune cells were subsequently analyzed based on the TISCH database.

RESULTS: This study identified eight characteristic genes that are significantly associated with LUAD prognosis and could serve as independent prognostic factors, with the low-risk group demonstrating a more favorable outcome. Additionally, a comprehensive nomogram was developed, showing a high degree of prognostic predictive value. The results from ssGSEA indicated that the low-risk group had higher immune cell infiltration. Ultimately, our findings revealed that the high-risk group exhibited heightened sensitivity to the Linsitinib, whereas the low-risk group demonstrated enhanced sensitivity to the OSI-027 drug.

CONCLUSION: The risk score exhibited robust prognostic capabilities, offering novel insights for assessing immunotherapy. This will provide a new direction to achieve personalized and precise treatment of LUAD in the future.},
}

Humans
*Adenocarcinoma of Lung/genetics/immunology/drug therapy
*Lung Neoplasms/genetics/drug therapy/immunology
Prognosis
*Immunotherapy/methods
*Telomere/genetics
Male
Female
Aging/genetics/immunology
Middle Aged
Nomograms
Aged
Biomarkers, Tumor/genetics

@article {pmid39755520,
year = {2025},
author = {Catalinas-Muñoz, E and Jiménez-Gómez, M and Díaz-Miravalls, J and Quezada-Loaiza, CA and Pérez-González, VL and De-Pablo-Gafas, A and Alonso-Moralejo, R},
title = {Impact of Telomere Shortening on Post-transplant Outcomes in Interstitial Lung Disease.},
journal = {Transplantation proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.transproceed.2024.12.004},
pmid = {39755520},
issn = {1873-2623},
abstract = {Shortened telomere length (STL) is associated with increased rates of interstitial lung diseases, malignancy, hematological disorders, and immunosuppressive treatment toxicities. In this single-center retrospective study, we aim to determine whether patients with interstitial lung diseases who have STL, as determined by quantitative PCR of buccal epithelial cells, exhibit worse post-transplant outcomes compared to recipients with normal telomere length. In our series of 26 patients, STL was associated with a higher incidence of chronic kidney disease following lung transplantation (100% vs 55%, P = .042). However, STL was not associated with an increased incidence of acute cellular rejection, infections, cytomegalovirus viremia, cytopenias, elevated liver enzymes, cancer diagnosis, venous thromboembolism, or mortality. Thus, lung transplant recipients with STL are at an increased risk of developing chronic kidney disease during the post-transplant period compared to those with normal telomere length.},
}

@article {pmid39754352,
year = {2025},
author = {Rodriguez, MD and Bay, RA and Ruegg, KC},
title = {Telomere Length Differences Indicate Climate Change-Induced Stress and Population Decline in a Migratory Bird.},
journal = {Molecular ecology},
volume = {},
number = {},
pages = {e17642},
doi = {10.1111/mec.17642},
pmid = {39754352},
issn = {1365-294X},
support = {006784//National Science Foundation Graduate Research Fellowship Program/ ; 62591-443863//National Geographic Society/ ; 1942313//National Science Foundation/ ; },
abstract = {Genomic projections of (mal)adaptation under future climate change, known as genomic offset, faces limited application due to challenges in validating model predictions. Individuals inhabiting regions with high genomic offset are expected to experience increased levels of physiological stress as a result of climate change, but documenting such stress can be challenging in systems where experimental manipulations are not possible. One increasingly common method for documenting physiological costs associated with stress in individuals is to measure the relative length of telomeres-the repetitive regions on the caps of chromosomes that are known to shorten at faster rates in more adverse conditions. Here we combine models of genomic offsets with measures of telomere shortening in a migratory bird, the yellow warbler (Setophaga petechia), and find a strong correlation between genomic offset, telomere length and population decline. While further research is needed to fully understand these links, our results support the idea that birds in regions where climate change is happening faster are experiencing more stress and that such negative effects may help explain the observed population declines.},
}

@article {pmid39750135,
year = {2024},
author = {Crous-Bou, M and Lázaro, I and Nadal-Zaragoza, N and Sala-Vila, A},
title = {Fatty acids and telomere length.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCO.0000000000001093},
pmid = {39750135},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: This narrative review includes the latest clinical and preclinical evidence on fatty acid exposure and telomere length, a widely accepted hallmark of aging.

RECENT FINDINGS: A large body of literature focused on n-3 (omega-3) polyunsaturated fatty acids (PUFAs). Observational studies reported beneficial associations with telomere length for self-reported consumption of n-3 PUFA-rich foods; for estimated intake of n-3 PUFAs; and for n-3 PUFAs blood-based biomarkers in most (but not all) studies involving lipidomics, a promising tool in the field. Benefits were also observed in preclinical studies using different mouse models. Regarding other lipids, inconsistent findings were observed for circulating linoleic acid, whereas inverse associations with telomere length were reported for the n-6/n-3 PUFA ratio. Finally, a study using Mendelian randomization reported that monounsaturated fatty acids and PUFAs have a positive effect on telomere length, whereas the opposite was observed for saturated fatty acids.

SUMMARY: Evidence supporting that n-3 PUFAs might have beneficial effects on maintaining telomere length reinforce the salutary effects of these dietary fats. Approach considering the n-6/n-3 PUFA ratio is discouraged because it is sustained in the incorrect assumption that all species from the n-6 and n-3 families are functionally equivalent.},
}

@article {pmid39747616,
year = {2025},
author = {Djelmis, J and Ivanisevic, M},
title = {Influence of subclinical hypothyroidism and brain-derived neurotropic factor on telomere length dynamics in type 1 diabetic pregnancies and their newborns.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {194},
pmid = {39747616},
issn = {2045-2322},
support = {IP2018-01-1284.//Hrvatska Zaklada za Znanost/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Diabetes Mellitus, Type 1/metabolism/genetics/blood ; *Hypothyroidism/metabolism ; Infant, Newborn ; *Brain-Derived Neurotrophic Factor/genetics/blood ; Adult ; *Telomere/metabolism/genetics ; Prospective Studies ; Fetal Blood/metabolism ; Pregnancy in Diabetics/metabolism ; Thyrotropin/blood ; Male ; Telomere Homeostasis ; Pregnancy Trimester, First ; Telomere Shortening ; },
abstract = {Thyroid dysfunctions are common in type 1 diabetes mellitus (T1DM) pregnancies, impacting embryogenesis and fetal neurodevelopment. This study investigates the effects of subclinical hypothyroidism and BDNF (Brain-derived neurotrophic factor) telomere length in T1DM mothers and their newborns. In a recent study, researchers found an inverse relationship between TSH (thyroid-stimulating hormone) levels and telomere length in the cord blood of newborns. This was prospective cohort analysis of 70 mothers and their newborns with T1DM. The study measured leukocyte telomere length (LTL) in maternal and neonatal samples. Subclinical hypothyroidism during the first trimester was characterized by TSH levels ranging from 2.5 to 5.0 mIU/L alongside normal free thyroxine (FT4) concentrations. In this study, we proved that maternal telomere length predicts telomere length in the newborn. Furthermore, we investigated the influence of maternal hypothyroidism on telomere length in the newborn. Maternal hypothyroidism in the first trimester of pregnancy has a strong influence on the shortening of newborn telomeres. BDNF has a positive effect on maternal and newborn telomere length. These results can have an important impact on the subsequent development of a child born to a diabetic mother. Health and disease associated with telomere length later in life may be programmed at birth.},
}

Humans
Female
Pregnancy
*Diabetes Mellitus, Type 1/metabolism/genetics/blood
*Hypothyroidism/metabolism
Infant, Newborn
*Brain-Derived Neurotrophic Factor/genetics/blood
Adult
*Telomere/metabolism/genetics
Prospective Studies
Fetal Blood/metabolism
Pregnancy in Diabetics/metabolism
Thyrotropin/blood
Male
Telomere Homeostasis
Pregnancy Trimester, First
Telomere Shortening

@article {pmid39747057,
year = {2025},
author = {Theulot, B and Tourancheau, A and Simonin Chavignier, E and Jean, E and Arbona, JM and Audit, B and Hyrien, O and Lacroix, L and Le Tallec, B},
title = {Telomere-to-telomere DNA replication timing profiling using single-molecule sequencing with Nanotiming.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {242},
pmid = {39747057},
issn = {2041-1723},
support = {Allocation doctorale//Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche (MENESR)/ ; Allocation doctorale//Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche (MENESR)/ ; FRM FDT202106013030//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; FRM EQU202203014910//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; NanoPoRep ANR-18-CE45-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; HUDROR ANR-19-CE12-0028//Agence Nationale de la Recherche (French National Research Agency)/ ; NanoPoRep ANR-18-CE45-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; HUDROR ANR-19-CE12-0028//Agence Nationale de la Recherche (French National Research Agency)/ ; },
mesh = {*Telomere/genetics/metabolism ; *Saccharomyces cerevisiae/genetics ; *DNA Replication Timing ; *Telomere-Binding Proteins/metabolism/genetics ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; DNA Replication ; DNA, Fungal/genetics/metabolism ; S Phase/genetics ; Single Molecule Imaging/methods ; Bromodeoxyuridine/metabolism ; Nanopore Sequencing/methods ; Repressor Proteins ; },
abstract = {Current temporal studies of DNA replication are either low-resolution or require complex cell synchronisation and/or sorting procedures. Here we introduce Nanotiming, a single-molecule, nanopore sequencing-based method producing high-resolution, telomere-to-telomere replication timing (RT) profiles of eukaryotic genomes by interrogating changes in intracellular dTTP concentration during S phase through competition with its analogue bromodeoxyuridine triphosphate (BrdUTP) for incorporation into replicating DNA. This solely demands the labelling of asynchronously growing cells with an innocuous dose of BrdU during one doubling time followed by BrdU quantification along nanopore reads. We demonstrate in S. cerevisiae model eukaryote that Nanotiming reproduces RT profiles generated by reference methods both in wild-type and mutant cells inactivated for known RT determinants. Nanotiming is simple, accurate, inexpensive, amenable to large-scale analyses, and has the unique ability to access RT of individual telomeres, revealing that Rif1 iconic telomere regulator selectively delays replication of telomeres associated with specific subtelomeric elements.},
}

*Telomere/genetics/metabolism
*Saccharomyces cerevisiae/genetics
*DNA Replication Timing
*Telomere-Binding Proteins/metabolism/genetics
Saccharomyces cerevisiae Proteins/metabolism/genetics
DNA Replication
DNA, Fungal/genetics/metabolism
S Phase/genetics
Single Molecule Imaging/methods
Bromodeoxyuridine/metabolism
Nanopore Sequencing/methods
Repressor Proteins

@article {pmid39741705,
year = {2024},
author = {Yang, F and Cai, H and Ren, Y and Huang, K and Gao, H and Qin, L and Wang, R and Chen, Y and Zhou, L and Zhou, D and Chen, Q},
title = {Association between telomere length and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1393825},
pmid = {39741705},
issn = {1664-2295},
abstract = {OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is highly prevalent among elderly individuals, and there is a strong correlation between telomere length and biological aging. However, there is limited evidence to elucidate the relationship between telomere length and iNPH. This study aimed to investigate the associations between telomere length and iNPH using the Mendelian randomization (MR) method.

METHODS: The genetic variants of telomere length were obtained from 472,174 UK Biobank individuals. Summary level data of iNPH were acquired from 218,365 individuals of the FinnGen consortium. Five MR estimation methods, including inverse-variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode, were used for causal inference. Comprehensive sensitivity analyses were conducted to test the robustness of the results. In addition, multivariable MR was further implemented to identify potential mechanisms in the causal pathway from telomere length to iNPH.

RESULTS: Genetically determined longer telomere length was significantly associated with decreased risk of iNPH (OR = 0.44, 95% CI 0.24-0.80; p = 0.008). No evident heterogeneity (Cochran Q = 138.11, p = 0.386) and pleiotropy (MR Egger intercept = 0.01, p = 0.514) were observed in the sensitivity analysis. In addition, multivariable MR indicated that the observed association was attenuated after adjustment for several vascular risk factors, including essential hypertension (IVW OR = 0.55, 95% CI 0.30-1.03; p = 0.061), type 2 diabetes (IVW OR = 0.71, 95% CI 0.09-5.39; p = 0.740) and coronary artery disease (IVW OR = 0.58, 95% CI 0.31-1.07; p = 0.082).

CONCLUSION: Our MR study revealed a strong negative correlation of telomere length with iNPH. The causal relationship might be driven by several vascular risk factors.},
}

@article {pmid39741153,
year = {2024},
author = {Yang, W and Zhou, H and Huang, J and Zhu, W and Hou, H and Li, H and Zhao, L and Zhang, J and Liu, J and Qin, C and Wang, L and Luo, H and Zhu, J and Xiao, F and Yao, J and Yang, C and Meng, H},
title = {Near telomere-to-telomere assembly of the Tarim pigeon (Columba livia) genome.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1455},
pmid = {39741153},
issn = {2052-4463},
mesh = {*Columbidae/genetics ; Animals ; *Genome ; *Telomere/genetics ; },
abstract = {Pigeons serve as important model animals and commercial poultry. The Tarim pigeon, as a breed of Columba livia, is a locally indigenous breed unique to China. While the genome of C. livia was published in 2013, its assembly was fragmented and incomplete. In this study, we generated a near telomere-to-telomere assembly of the pigeon genome using the sequencing platform of PacBio HiFi, Nanopore long reads and Hi-C. The assembled genome spans 1295.8 Mb, with a contig N50 size of 49 Mb and a scaffold N50 size of 85 Mb. Approximately 98.4% of the assembly is anchored onto 41 chromosomes, with a BUSCO assessment indicating a completeness of 97.2%. And telomeres were identified at both ends of the four chromosomes. A total of 21,450 genes were annotated. The genome assembly of C. livia lays the foundation for understanding their genetic composition and evolutionary history and contributes to the pigeon breeding industry. Additionally, it will provide a basis for further management and conservation of pigeon breed diversity.},
}

*Columbidae/genetics
Animals
*Genome
*Telomere/genetics

@article {pmid39738483,
year = {2024},
author = {Dewulf, M and Pascottini, OB and Heirbaut, S and Meesters, M and Martens, DS and Nawrot, TS and Zhang, M and Jing, XP and Vandaele, L and Fievez, V and Van Eetvelde, M and Opsomer, G},
title = {Shortening of the telomere length during the transition period of dairy cows in relation to biological stress.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31756},
pmid = {39738483},
issn = {2045-2322},
support = {1SH5N24N//Fonds Wetenschappelijk Onderzoek/ ; 12X9623N//Fonds Wetenschappelijk Onderzoek/ ; LA170830//Agentschap Innoveren en Ondernemen/ ; },
mesh = {Animals ; Cattle ; Female ; *Telomere Shortening ; *Stress, Physiological ; Oxidative Stress ; Milk/metabolism ; Biomarkers/blood ; Telomere/metabolism ; Lactation ; Dairying ; },
abstract = {Telomere length (TL) is a recognized biomarker for ageing in multiple species. In dairy cattle, the transition period is considered a very stressful period. We hypothesized that TL shortens during this period. Holstein cows (n = 61) were followed during the transition period. Blood and milk samples were collected at - 7, 3, 6, 9, 21d relative to calving to determine concentrations of oxidative, energetic metabolic, and inflammatory markers. Average relative leukocyte TL was measured by a modified qPCR protocol 7d before and 21d after parturition. We confirmed TL attrition during the transition period (P = 0.02), as TL was 1.05 ± 0.229 (mean ± SD) before, and 0.97 ± 0.191 (mean ± SD) after parturition. Univariable analyses assessed associations between blood markers and TL shortening. Greater plasma oxidative parameters, including oxidized glutathione and glutathione peroxidase, were positively and negatively (respectively) associated with TL attrition. Higher blood α- and β-globulin were all positively associated, while IGF-1, albumin-globulin ratio and albumin were negatively associated with TL attrition. Greater serum amyloid A and haptoglobin were linked with greater TL shortening. This study reveals significant TL shortening during the transition period in dairy cows and identifies significant associations with oxidative stress, metabolic stress, and inflammation. While these associations are observed, no causality can be established. Our findings suggest the need for further research to explore the effects of transition-related stress on TL dynamics.},
}

Animals
Cattle
Female
*Telomere Shortening
*Stress, Physiological
Oxidative Stress
Milk/metabolism
Biomarkers/blood
Telomere/metabolism
Lactation
Dairying

@article {pmid39738205,
year = {2024},
author = {Guillen-Parra, M and Lin, J and Prather, AA and Wolkowitz, OM and Picard, M and Epel, ES},
title = {The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31589},
pmid = {39738205},
issn = {2045-2322},
support = {1R01AG030424-01A2/NH/NIH HHS/United States ; 1R01AG030424-01A2/NH/NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/metabolism ; Female ; *Mitochondria/metabolism ; Longitudinal Studies ; *Leukocytes, Mononuclear/metabolism ; Male ; *Telomere/metabolism ; Adult ; Stress, Psychological/metabolism ; Telomere Shortening ; Child ; Autism Spectrum Disorder/metabolism/genetics ; Telomere Homeostasis ; Middle Aged ; },
abstract = {Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance. In this observational longitudinal study, we examined in peripheral blood mononuclear cells (PBMCs), whether MHI predicted changes in telomerase activity over a 9-month period, thus impacting telomere maintenance over this same period of time. We secondarily examined the role of chronic stress, by comparing these relationships in mothers of children with an autism spectrum disorder (caregivers) vs. mothers of a neurotypical child (controls). Here we show that both chronic stress exposure and lower MHI independently predicted decreases in telomerase activity over the subsequent 9 months. Finally, changes in telomere length were directly related with changes in telomerase activity, and indirectly with MHI and chronic stress, as revealed by a path analysis. These results highlight the potential role of chronic stress and MHI as drivers of telomere attrition in human PBMCs, through an impairment of both energy-transformation capacity and telomerase production.},
}

Humans
*Telomerase/metabolism
Female
*Mitochondria/metabolism
Longitudinal Studies
*Leukocytes, Mononuclear/metabolism
Male
*Telomere/metabolism
Adult
Stress, Psychological/metabolism
Telomere Shortening
Child
Autism Spectrum Disorder/metabolism/genetics
Telomere Homeostasis
Middle Aged

@article {pmid39737735,
year = {2025},
author = {Marasco, V and Boner, W and Griffiths, K and Raveh, S and Monaghan, P},
title = {Hidden Causes of Variation in Offspring Reproductive Value: Negative Effects of Maternal Breeding Age on Offspring Telomere Length Persist Undiminished Across Multiple Generations.},
journal = {Ecology letters},
volume = {28},
number = {1},
pages = {e70043},
doi = {10.1111/ele.70043},
pmid = {39737735},
issn = {1461-0248},
support = {I 6634//Austrian Science Fund/ ; M2520-B29//Austrian Science Fund/ ; 101020037//H2020 European Research Council/ ; 268926//H2020 European Research Council/ ; BB/P009174/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Animals ; Female ; *Finches/physiology/genetics ; *Reproduction ; *Longevity ; Telomere ; Male ; Telomere Shortening ; Aging ; },
abstract = {Offspring of older breeders frequently show reduced longevity, which has been linked to shorter offspring telomere length. It is currently unknown whether such telomere reduction persists beyond a single generation, as would be the case if germline transmission is involved. In a within-grandmother, multi-generational study using zebra finches, we show that the shorter telomeres observed in F1 offspring of older mothers are still present in the F2 generation even when the breeding age of their F1 mothers is young. The effect was substantial: 43% shorter telomeres in grandoffspring from the 'grandmother old at breeding' line compared with those from the 'grandmother young at breeding' line. Shorter telomeres at fledging in this species are associated with a reduction in lifespan. Our data demonstrate the need to look beyond a single generation to explain inter-individual variation in ageing rates and thereby variation in optimal allocation of age-specific reproductive effort.},
}

Animals
Female
*Finches/physiology/genetics
*Reproduction
*Longevity
Telomere
Male
Telomere Shortening
Aging

@article {pmid39736866,
year = {2024},
author = {Liu, S and Xu, L and Cheng, Y and Liu, D and Zhang, B and Chen, X and Zheng, M},
title = {Decreased telomerase activity and shortened telomere length in infants whose mothers have gestational diabetes mellitus and increased severity of telomere shortening in male infants.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1490336},
pmid = {39736866},
issn = {1664-2392},
mesh = {Humans ; *Diabetes, Gestational/metabolism ; Female ; Pregnancy ; Male ; *Telomerase/metabolism/genetics ; *Telomere Shortening ; Adult ; Infant, Newborn ; *Fetal Blood/metabolism ; *Oxidative Stress ; Telomere/metabolism ; Case-Control Studies ; Blood Glucose/metabolism ; Telomere Homeostasis/physiology ; },
abstract = {OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring.

METHODS: We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels.

RESULTS: The length of telomeres in umbilical CBMCs in the GDM group was significantly shorter than that in the Ctrl group (P<0.001), and the shortening of telomeres in male infants in the GDM group was more significant than that in the Ctrl group (P<0.001) after adjustment for Pre-pregnancy body mass index (PBMI), Pregnancy weight gain (PGW), and Triglyceride (TG) as confounding factors. In addition, the TE expression level in the GDM group was lower after adjustment. There was no statistically significant difference in oxidative stress hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups. TL was positively correlated with TE activity, and both were negatively correlated with blood glucose levels. There was no correlation between TL and Gestational age (GA), PBMI, PGW, or TG levels.

CONCLUSION: The poor intrauterine environment in pregnant women with GDM increases telomere attrition and reduces TE activity, which may be potential genetic risk factors for an increased risk of metabolic diseases in offspring later in life due to intrauterine reprogramming.},
}

Humans
*Diabetes, Gestational/metabolism
Female
Pregnancy
Male
*Telomerase/metabolism/genetics
*Telomere Shortening
Adult
Infant, Newborn
*Fetal Blood/metabolism
*Oxidative Stress
Telomere/metabolism
Case-Control Studies
Blood Glucose/metabolism
Telomere Homeostasis/physiology

@article {pmid39735642,
year = {2024},
author = {Yi, J and Guo, H and Jiang, C and Duan, J and Xue, J and Zhao, Y and He, W and Xia, L},
title = {Leukocyte telomere length decreased the risk of mortality in patients with alcohol-associated liver disease.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1462591},
pmid = {39735642},
issn = {1664-2392},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Leukocytes/metabolism/pathology ; *Liver Diseases, Alcoholic/mortality ; *Telomere ; Adult ; Nutrition Surveys ; Prognosis ; Telomere Homeostasis ; Aged ; Risk Factors ; Cardiovascular Diseases/mortality ; },
abstract = {BACKGROUND: It is necessary to find latent indicators to predict the survival of alcohol-associated liver disease (ALD) patients. Leukocyte telomere length (LTL) was regarded as an indicator of prognosis in several diseases. However, the relationships between LTL and survival as well as cause-specific mortality in ALD patients were still unknown.

OBJECTIVE: This study aimed at exploring the underlying link between LTL and the risk of mortality in patients with ALD.

METHODS: The LTL and survival data were gathered from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The connection between LTL and mortality was assessed by Cox regression models and stratified analyses. The non-linear relationship was explored by restricted cubic spline (RCS) analysis. Sensitivity analyses were used to evaluate the robustness of our findings.

RESULTS: LTL was a negative factor for all-cause mortality (all p-value < 0.05). The risk of cardiovascular disease (CVD)-related death was decreased in Q3 (p < 0.001) and Q4 levels of LTL (p < 0.001) compared with the Q1 group. Shorter LTL resulted in higher cancer-caused mortality (p = 0.03) in the Q2 group. Longer LTL improved survival especially for elder patients (p for trend < 0.001) or men (p for trend = 0.001). Moreover, there were L-shaped correlations between LTL and all-cause mortality (p for non-linearity = 0.02), as well as cancer-related mortality (p for non-linearity < 0.001). Four sensitivity analyses proved the robustness of our findings.

CONCLUSION: Our research found that longer LTL improved survival in patients with ALD and decreased CVD and cancer-related mortality. LTL decreased all-cause mortality especially for patients older than 65 years or men. LTL might be a useful biomarker for prognosis among patients with ALD. More prospective studies are needed to assess the relevance between LTL and mortality and explore the underlying mechanisms between them.},
}

Humans
Male
Female
Middle Aged
*Leukocytes/metabolism/pathology
*Liver Diseases, Alcoholic/mortality
*Telomere
Adult
Nutrition Surveys
Prognosis
Telomere Homeostasis
Aged
Risk Factors
Cardiovascular Diseases/mortality

@article {pmid39735175,
year = {2025},
author = {Fernández Alonso, AM and Varikasuvu, SR and Pérez-López, FR},
title = {Telomere length and telomerase activity in men and non-pregnant women with and without metabolic syndrome: a systematic review and bootstrapped meta-analysis.},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {1},
pages = {24},
pmid = {39735175},
issn = {2251-6581},
abstract = {PURPOSE: We performed a systematic review and meta-analysis to examine the associations between telomere length and telomerase activity in subjects with and without metabolic syndrome (MetS).

METHODS: The meta-analysis protocol was registered in the PROSPERO database. The PubMed, Embase, Cochrane Library, and LILACS databases were searched for studies reporting telomere length or telomerase activity in adult men and non-pregnant women with and without MetS. The risk of bias was assessed with the Newcastle-Ottawa Scale. Random effects and inverse variance methods were used to meta-analyze associations. We conducted a bootstrapped analysis to test the accuracy of clinical results.

RESULTS: Five studies reported telomere length and two studies telomerase activity. There was no significant difference in telomere length (standardized mean difference [SMD]: 0.10, 95% confidence interval [CI]: -0.07, 0.28, I [2]: 54%), between subjects of similar age (mean difference: 2.68, 95%CI: -0.04, 5.40 years) with and without the MetS. Subjects with MetS displayed significantly higher body mass index, triglycerides, and blood pressure, and lower HDL-cholesterol values than subjects without the syndrome. A bootstrapping mediation analysis of telomere length confirmed the clinical results. There was no significant difference in telomerase activity (SMD: 1.19, 95% CI -0.17, 2.55, I [2]: 93%) between subjects with and without the MetS.

CONCLUSION: There were no significant differences of telomere length and telomerase activity in patients with MetS and subjects of similar age without the syndrome.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-024-01513-4.},
}

@article {pmid39735156,
year = {2024},
author = {Giridharan, S},
title = {Yoga and Telomeres: A Path to Cellular Longevity?.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e74552},
pmid = {39735156},
issn = {2168-8184},
abstract = {Telomeres, which protect the chromosomal ends, are vital for cellular senescence and health. Telomere shortening, often due to stress, inflammation, and oxidative damage, is linked to age-related diseases such as cancer, cardiovascular issues, and neurodegeneration. Evidence suggests that meditation may affect telomere dynamics by reducing stress and inflammation and improving emotional regulation. Clinical trials have demonstrated that the effectiveness of these practices in increasing telomerase activity and maintaining telomere length varies by type, intensity, and duration of the practice. Yoga and meditation boost cellular resilience by lowering stress, inflammation, and oxidative damage and enhancing neuroendocrine regulation. Despite promising results, study design variability and limited long-term data require further research. Future studies should identify the most effective components, dose-response relationships, and long-term effects across populations. Increasing evidence suggests that yoga and meditation could be key preventive and therapeutic strategies to improve cellular health and longevity.},
}

@article {pmid39730524,
year = {2024},
author = {Inui, T and Kawamura, N and Yamamura, M and Kubo, K and Yamakage, H and Satoh-Asahara, N and Ogawa, Y and Katsuura, G},
title = {Oral intake of degalactosylated whey protein increases peripheral blood telomere length in young and aged mice.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30859},
pmid = {39730524},
issn = {2045-2322},
mesh = {Animals ; *Whey Proteins/administration & dosage ; *Telomerase/genetics/metabolism ; Mice ; *Telomere/metabolism/genetics ; Administration, Oral ; *Aging ; Male ; Telomere Homeostasis/drug effects ; RNA, Messenger/genetics/metabolism ; RNA/metabolism/genetics ; },
abstract = {In order to elucidate novel actions of degalactosylated whey protein (D-WP) in comparison with intact whey protein (WP), the effects of oral intake of D-WP on peripheral blood telomere length and telomerase were examined in young and aged mice. In young mice, peripheral blood telomere length was significantly elongated following oral intake of D-WP for 4 weeks. mRNA expression of both telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) was significantly increased in the peripheral blood following oral intake of D-WP for 4 weeks. In aged mice, peripheral blood telomere length was significantly decreased as compared with that of young mice, and significantly restored to the level of young mice drinking water by the oral intake of D-WP for 4 weeks. The mRNA expression of peripheral blood TERT and TERC mRNA in aged mice significantly decreased as compared with the level in young mice drinking water, and was significantly restored to the level of expression of young mice drinking water by oral intake of D-WP for 4 weeks. These results suggest that D-WP, but not WP, potently increases peripheral blood telomere length accompanied by increased mRNA expression of TERT and TERC in both young and aged mice.},
}

Animals
*Whey Proteins/administration & dosage
*Telomerase/genetics/metabolism
Mice
*Telomere/metabolism/genetics
Administration, Oral
*Aging
Male
Telomere Homeostasis/drug effects
RNA, Messenger/genetics/metabolism
RNA/metabolism/genetics

@article {pmid39728924,
year = {2024},
author = {Mukherjee, AK and Dutta, S and Singh, A and Sharma, S and Roy, SS and Sengupta, A and Chatterjee, M and Vinayagamurthy, S and Bagri, S and Khanna, D and Verma, M and Soni, D and Budharaja, A and Bhisade, SK and Anand, V and Perwez, A and George, N and Faruq, M and Gupta, I and Sabarinathan, R and Chowdhury, S},
title = {Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {39728924},
issn = {2050-084X},
support = {IA/S/18/2/504021//Wellcome Trust DBt India Alliance/ ; },
mesh = {Humans ; *Tumor Microenvironment ; *Signal Transduction ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; Animals ; *Telomere/metabolism ; Cell Line, Tumor ; Mice ; Female ; Triple Negative Breast Neoplasms/genetics/immunology/metabolism/pathology ; Gene Expression Regulation, Neoplastic ; Promoter Regions, Genetic ; Receptors, Interleukin-1 Type I ; },
abstract = {Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the IL1R1 promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like IL6, IL8, and TNF. Further, IL1R1 expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with IL1R1 expression. The use of both IL1 Receptor antagonist (IL1RA) and IL1R1 targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.},
}

Humans
*Tumor Microenvironment
*Signal Transduction
*Telomeric Repeat Binding Protein 2/metabolism/genetics
Animals
*Telomere/metabolism
Cell Line, Tumor
Mice
Female
Triple Negative Breast Neoplasms/genetics/immunology/metabolism/pathology
Gene Expression Regulation, Neoplastic
Promoter Regions, Genetic
Receptors, Interleukin-1 Type I

@article {pmid39726249,
year = {2024},
author = {Li, X and Hu, D and Zhang, M and Wang, W},
title = {Human telomere length detected by quantitative fluorescent in situ hybridization: overlooked importance and application.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10408363.2024.2441733},
pmid = {39726249},
issn = {1549-781X},
abstract = {The technique of Quantitative Fluorescence in Situ Hybridization (Q-FISH) plays a crucial role in determining the length of telomeres for studies in molecular biology and cytogenetics. Throughout the years, the use of Q-FISH for measuring telomere length has made substantial contributions to research in aging, cancer, and stem cells. The objective of this analysis is to delineate the categorization, fundamental concepts, pros and cons, and safety measures of Q-FISH in telomere length analysis, encapsulate, and anticipate its principal uses across diverse human biomedical research fields.},
}

@article {pmid39724986,
year = {2024},
author = {Wang, X and Gao, Z and Liu, Y and Wang, P and Fang, X and Sun, M and Ma, K and Wang, B and Han, W},
title = {Design and synthesis of novel structures with anti-tumor effects: Targeting telomere G-quadruplex and hTERT.},
journal = {Bioorganic & medicinal chemistry letters},
volume = {},
number = {},
pages = {130083},
doi = {10.1016/j.bmcl.2024.130083},
pmid = {39724986},
issn = {1464-3405},
abstract = {The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT. The 144 structures were designed by summarising the common structure-activity relationship of G4 stabilisers and hTERT inhibitors.Molecular docking and mtQSAR activity prediction experiments finally identified a16 and a35 as the optimal structures. Subsequently their derivative compounds b1-b6 were synthesised,with b4 exhibiting the most pronounced inhibitory effect on tumour cells. The ability of b4 to distinguish single-stranded DNA, double-stranded DNA and telomere G4 was verified by fluorescence experiment, and the stable combination of b4 and hTERT was verified by molecular dynamics simulation. This suggests that the structural design of targeting G4 and hTERT is reasonable and has anti-tumor potential.},
}

@article {pmid39719503,
year = {2024},
author = {Xue, CC and Nusinovici, S and Yu, M and Chee, ML and Teo, K and Su, X and Cheung, CMG and Sabanayagam, C and Cheng, CY and Tham, YC},
title = {Associations between shorter leucocyte telomere length and increased risk of age-related macular degeneration in women: insights from the United Kingdom Biobank study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {39719503},
issn = {1476-5454},
support = {NMRC/LCG/004/2018; NMRC/MOH/ HCSAINV21nov-0001//Ministry of Health -Singapore (MOH)/ ; },
abstract = {OBJECTIVES: To determine the association between telomere length (TL) and age-related macular degeneration (AMD) and examine the potential variations with sex and ethnicity.

METHODS: Population-based, cross-sectional study. A total of 52,083 participants from the UK Biobank were included. Leucocyte TL, measured using quantitative polymerase chain reaction assay, was presented as the ratio of telomere repeat copy number relative to that of a single copy gene, and then log-transformed and Z-standardised. AMD cases were identified based on a combination of in-patient, self-reported and primary care data, and furtherly classified as early, intermediate and late AMD using the Beckmann classification system (based on more severe eye).

RESULTS: Among the 52,083 participants aged 60.2 ± 5.4 years, 725 were any-AMD cases. AMD patients had shorter TL than those without AMD (-0.22 ± 0.95 vs. -0.10 ± 0.99, P = 0.001). In multivariable model, shorter TL (per standard deviation) was significantly associated with higher odds of AMD in Whites (OR:1.09; 95% CI: 1.01-1.18; P = 0.036). When stratified by sex and ethnicity, this association was only significant in White women (OR:1.14; 95%CI: 1.02, 1.27; P = 0.018), but not in men and nonwhite populations (all P ≥ 0.335). Among white women, the association was more pronounced (OR:1.47; 95%CI:1.23-1.77; P < 0.001) for intermediate/late AMD but not for early AMD (P = 0.789).

CONCLUSIONS: Shorter TL was associated with any AMD in white women but not in men and other ethnicities. Our findings highlight the potential role of telomere length in the pathogenesis of AMD and the importance of considering sex and ethnicity variation in this research area.},
}

@article {pmid39719362,
year = {2024},
author = {Mohamed, HABE and Agus, HH and Palabiyik, B},
title = {A novel method for telomere length detection in fission yeast.},
journal = {FEMS yeast research},
volume = {},
number = {},
pages = {},
doi = {10.1093/femsyr/foae040},
pmid = {39719362},
issn = {1567-1364},
abstract = {Fission yeast is the ideal model organism for studying telomere maintenance in higher eukaryotes. Telomere length has been directly correlated with life expectancy and the onset of aging-related diseases in mammals. In this study, we developed a novel simple, and reproducible method to measure the telomere length, by investigating the effect of Caffeine and Cisplatin on the telomere length in fission yeast. Hydroxyurea synchronized fission yeast cells were exposed to 62 μM Cisplatin and 8.67 mM Caffeine treatments for 2 hours then their telomere lengths were evaluated with two different methods. first: the quantitative PCR assay was used as a confirmative method where telomere length was determined relative to a single copy gene in the genome. Second: the newly developed method standard PCR/ImageJ assay assessed the telomere length based on the amplified PCR band intensity using a set of telomere primers, reflecting telomeric sequence availability in the genome. Both methods show a significant decrease and a notable telomere lengthening in response to Cisplatin and Caffeine treatments respectively. The finding supports the accuracy and productivity of the standard PCR/ImageJ assay as it can serve as a quick screening tool to study the effect of suspected chemotherapeutic and anti-aging drugs on telomere length in fission yeast.},
}

@article {pmid39718587,
year = {2024},
author = {Spinou, M and Naska, A and Nelson, CP and Codd, V and Samani, NJ and Bountziouka, V},
title = {Correction: Micronutrient intake and telomere length: findings from the UK Biobank.},
journal = {European journal of nutrition},
volume = {64},
number = {1},
pages = {53},
doi = {10.1007/s00394-024-03543-3},
pmid = {39718587},
issn = {1436-6215},
}

@article {pmid39715566,
year = {2024},
author = {Mony, V and Subramanian, S and Kanchibhotla, D},
title = {Sudarshan Kriya Yoga Promotes Telomere Elongation: A Pilot Study.},
journal = {Alternative therapies in health and medicine},
volume = {},
number = {},
pages = {},
pmid = {39715566},
issn = {1078-6791},
abstract = {BACKGROUND: Telomere length has been identified as a marker for biological aging and stressful body states. Mind-body interventions for stress reduction such as meditation, yoga, and pranayama have been previously tested to evaluate their efficacy in restricting telomere shortening.

PRIMARY STUDY OBJECTIVE: In this study, the effect of Sudarshan Kriya Yoga (SKY) is investigated for its influence on telomere length.

METHODS: Isolating the genomic DNA from the blood, relative telomere length was found using a quantitative PCR method for the SKY intervention group and a control group. Telomere maintenance gene expression was assessed from a microarray gene expression dataset.

SETTING: Sri Sri Institute for Advanced Research, Bangalore.

PARTICIPANTS: Employees, working at a corporate organization were the participants of this study. 11 individuals were enrolled in the intervention group while 5 were enrolled in the control group.

INTERVENTION: The integrated yoga-meditation practice, Sudarshan Kriya Yoga (SKY).

PRIMARY OUTCOME MEASURES: The relative telomere length and the expression of telomere maintenance genes from the genomic DNA isolated from the participants' blood samples.

RESULTS: Telomere length after SKY increased significantly compared to the baseline. However, in the controls, the corresponding change was insignificant. The telomere maintenance gene expression analysis reveals an intervention response conducive to telomere length extension at the molecular level.

CONCLUSION: The extension of telomere length after SKY underscores its efficacy in stress reduction and improved health-span.},
}

@article {pmid39713403,
year = {2024},
author = {Smeds, L and Kamali, K and Kejnovská, I and Kejnovský, E and Chiaromonte, F and Makova, KD},
title = {Non-canonical DNA in human and other ape telomere-to-telomere genomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.09.02.610891},
pmid = {39713403},
issn = {2692-8205},
abstract = {Non-canonical (non-B) DNA structures-e.g., bent DNA, hairpins, G-quadruplexes, Z-DNA, etc.-which form at certain sequence motifs (e.g., A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies, and occupy 9-15%, 9-11%, and 12-38% of autosomes, and chromosomes X and Y, respectively. Functional regions (e.g., promoters and enhancers) and repetitive sequences are enriched in non-B DNA motifs. Non-B DNA motifs concentrate at short arms of acrocentric chromosomes in a pattern reflecting their satellite repeat content and might contribute to satellite dynamics in these regions. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.},
}

@article {pmid39709617,
year = {2024},
author = {Helmstetter, N and Harrison, K and Gregory, J and Harrison, J and Ballou, E and Farrer, RA},
title = {A near-complete telomere-to-telomere genome assembly for Batrachochytrium dendrobatidis GPL JEL423 reveals a larger CBM18 gene family and a smaller M36 metalloprotease gene family than previously recognised.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkae304},
pmid = {39709617},
issn = {2160-1836},
abstract = {Batrachochytrium dendrobatidis (Bd) is responsible for mass extinctions and extirpations of amphibians, mainly driven by the Global Panzootic Lineage (BdGPL). BdGPL isolate JEL423 is a commonly used reference strain in studies exploring the evolution, epidemiology and pathogenicity of chytrid pathogens. These studies have been hampered by the fragmented, erroneous and incomplete B. dendrobatidis JEL423 genome assembly, which includes long stretches of ambiguous positions, and poorly resolved telomeric regions. Here we present and describe a substantially improved, near telomere-to-telomere genome assembly and gene annotation for B. dendrobatidis JEL423. Our new assembly is 24.5 Mb in length, ∼800 kb longer than the previously published assembly for this organism, comprising 18 nuclear scaffolds and 2 mitochondrial scaffolds and including an extra 839 kb of repetitive sequence. We discovered that the patterns of aneuploidy in B. dendrobatidis JEL423 have remained stable over approximately 5 years. We found that our updated assembly encodes fewer than half the number of M36 metalloprotease genes predicted in the previous assembly. In contrast, members of the crinkling and necrosis gene family were found in similar numbers to the previous assembly. We also identified a more extensive carbohydrate binding module 18 gene family than previously observed. We anticipate our findings, and the updated genome assembly will be a useful tool for further investigation of the genome evolution of the pathogenic chytrids.},
}

@article {pmid39707531,
year = {2024},
author = {Lehodey, A and Kaliman, P and Palix, C and de Florès, R and Touron, E and Turpin, AL and Fauvel, S and Mézenge, F and Landeau, B and Chocat, A and Vrillon, A and Paquet, C and Vivien, D and de La Sayette, V and Chételat, G and Poisnel, G and , },
title = {Association of critically short telomeres with brain and blood markers of ageing and Alzheimer's disease in older adults.},
journal = {Alzheimer's research & therapy},
volume = {16},
number = {1},
pages = {269},
pmid = {39707531},
issn = {1758-9193},
mesh = {Humans ; Male ; Aged ; Female ; *Alzheimer Disease/blood/genetics/diagnostic imaging ; Cross-Sectional Studies ; *Aging/genetics/blood ; *Brain/diagnostic imaging/pathology/metabolism ; *Biomarkers/blood ; *Telomere Shortening/physiology ; Aged, 80 and over ; Apolipoprotein E4/genetics ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults.

METHODS: This cross-sectional study used baseline data of 129 community-dwelling cognitively healthy older adults from the Age-Well trial (NCT02977819), aged 65 years and older enrolled between 2016 and 2018, in France. Using linear regressions, we analyzed the relationship between an innovative marker of telomere shortening, the percentage of CST (%CST), structural, functional and molecular neuroimaging outcomes, and multiple blood-based biomarkers related to AD pathophysiology. The effect of apolipoprotein E ε4 genotype (APOE4) was assessed on these relationships using interaction analysis.

RESULTS: A higher %CST was associated with lower global kurtosis fractional anisotropy (β = -.230; P = .010), particularly in frontal and temporal regions. A higher %CST was also related to higher plasma levels of Neurofilament light chain (β = .195; P = .020) and a lower subiculum volume (β = -.206; P = .020), although these associations did not meet the threshold for multiple comparisons. %CST was not associated with AD-related neuroimaging markers, including the AD-sensitive gray matter pattern (β = -.060; P = .441), glucose metabolism pattern (β = -.099; P = .372), brain perfusion pattern (β = -.106; P = .694) or hippocampus volume (β = -.106; P = .194). In APOE4 carriers, higher %CST was associated with lower subiculum (β = -.423; P = 0.003), DG (β = -.410; P = 0.018) and CA1 volumes (β = -.373; P = 0.024), even though associations with DG and CA1 volumes did not survive multiple comparison.

CONCLUSIONS: Although an increase in %CST does not appear to be directly linked to the pathophysiology of AD in cognitively healthy older adults, it could heighten the susceptibility of APOE4 carriers to develop AD plausibly due to greater vulnerability to age-related effects. However, longitudinal studies would be necessary to determine whether %CST influences the development and progression of AD later in life.},
}

Humans
Male
Aged
Female
*Alzheimer Disease/blood/genetics/diagnostic imaging
Cross-Sectional Studies
*Aging/genetics/blood
*Brain/diagnostic imaging/pathology/metabolism
*Biomarkers/blood
*Telomere Shortening/physiology
Aged, 80 and over
Apolipoprotein E4/genetics
Neurofilament Proteins/blood

@article {pmid39704849,
year = {2024},
author = {Alwehaidah, MS and Al-Awadhi, R and AlRoomy, M and Baqer, TA},
title = {Impact of telomere length for risk assessment and prognosis in papillary thyroid cancer depending on the clinicopathological features.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {2},
pmid = {39704849},
issn = {1617-4623},
mesh = {Humans ; Female ; Male ; *Thyroid Cancer, Papillary/genetics/pathology/mortality ; Middle Aged ; Prognosis ; *Thyroid Neoplasms/genetics/pathology ; *Telomere/genetics ; Adult ; Risk Assessment/methods ; Aged ; Case-Control Studies ; Kaplan-Meier Estimate ; Telomere Homeostasis/genetics ; },
abstract = {OBJECTIVE: . Despite the establishment of a link between telomere status and carcinogenesis, lack of a consensus in the cancer specific pattern of telomere length has a severe impact on the use of relative telomere length (RTL) in cancer diagnosis. The disparity in assessing the relationship between telomere length and cancer risk is complex and may vary as it is influenced by other factors. The objective of this study is to thoroughly examine the intricate relationship between telomere length and cancer incidence in Papillary Thyroid Cancer (PTC) depending on the tumor type, stage, patients' sex and age. Therefore, the current study is focused on the association of RTL in PTC patients with different clinicopathological characteristics and compared with controls to determine the risk of PTC and expected survival time after surgery.

METHOD: . This study included 126 patients with PTC and 80 controls. RTL in thyroid tissues was measured using quantitative (q) PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Kaplan-Meier and Cox regression were used to analyze postsurgical outcomes.

RESULT: . The RTL of patients was significantly shorter than that of controls. A short RTL was significantly correlated with an elevated risk of PTC in patients aged ≥ 55 years, female sex, classic subtype, and tumor size > 2 cm. A short RTL did not affect the overall survival of patients with PTC; however, it was associated with poor survival in patients with tumor size > 2 cm and tumor invasion.

CONCLUSION: . This unique study combines the use of RTL with various clinicopathological features of patients with PTC. In conclusion, RTL is a promising tumor marker that correlates with the clinical characteristics of patients with PTC. Specifically, RTL < 0.6 could be used with age, sex, tumor size > 2 cm and tumor invasion to predict the risk of PTC development and prognosis of the disease. This study will open new horizon in the use of molecular marker such as RTL for understanding its association with increased cancer risk in patients with different clinicopathological features.},
}

Humans
Female
Male
*Thyroid Cancer, Papillary/genetics/pathology/mortality
Middle Aged
Prognosis
*Thyroid Neoplasms/genetics/pathology
*Telomere/genetics
Adult
Risk Assessment/methods
Aged
Case-Control Studies
Kaplan-Meier Estimate
Telomere Homeostasis/genetics

@article {pmid39701464,
year = {2024},
author = {Zhang, B and Yuan, F and Zhang, L and Xia, L and Zhu, X and Lu, S and Wang, L and He, Z},
title = {From potential biomarker to clinical predictive models: Integrating socioeconomic status and sleep into leukocyte telomere length of depression and anxiety research.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.12.063},
pmid = {39701464},
issn = {1573-2517},
}

@article {pmid39697975,
year = {2024},
author = {Guillen-Parra, M and Barcenas-Flores, R and Velando, A and Wiley, A and Montoya, B and Torres, R},
title = {Sex-Specific Variation in Foraging Behavior is Related to Telomere Length in a Long-Lived Seabird.},
journal = {Ecology and evolution},
volume = {14},
number = {12},
pages = {e70732},
pmid = {39697975},
issn = {2045-7758},
abstract = {Foraging during breeding is a demanding activity linked to breeding investment and possibly constrained by individual quality. Telomere length, the protective nucleoproteins located at the ends of the chromosomes, is considered a trait reflecting somatic maintenance and individual quality. Therefore, foraging effort and parental investment may be positively related to telomere length, if individuals with longer telomeres are of better quality and thus able to maintain better body condition and allocate more resources to parental activities. In the brown booby (Sula leucogaster), we investigated if telomere length is related to body mass (a proxy of condition) and whether variation in foraging behavior and provisioning effort is related to telomere length or body mass. Then, we explored whether variation in foraging and provisioning influences the chick mass growth rate. In 34 pairs nesting in Isla de San Jorge, in the Gulf of California, México, we sampled their blood to estimate telomere length, measured their body mass, and for 10 days, recorded their foraging behavior via global positioning system (GPS) loggers and their chick provisioning rate and chicks' mass growth rate. We found a positive relationship between parents' body mass and telomere length. Body mass did not affect foraging behavior. Females with longer telomeres were more prone to travel longer distances toward offshore and deeper waters than females with shorter telomeres. In contrast, males with longer telomere lengths performed more nearshore foraging trips than males with shorter telomeres. The chick provisioning rate was unrelated to telomere length or body mass, but females fed the chick at a rate 2.4 times greater than males. Females' offshore foraging, but not males', was positively related to chick mass growth rate. Our results suggest that individual quality, indicated by telomere length, is an important driver of sex-specific, between-individual variation in foraging behavior, indirectly affecting offspring condition.},
}

@article {pmid39695676,
year = {2024},
author = {Skåra, KH and Lee, Y and Jugessur, A and Gjessing, HK and Aviv, A and Brumpton, B and Næss, Ø and Hernáez, Á and Hanevik, HI and Magnus, P and Magnus, MC},
title = {Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.},
journal = {BMC medicine},
volume = {22},
number = {1},
pages = {580},
pmid = {39695676},
issn = {1741-7015},
support = {947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 320656//Norges Forskningsråd/ ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; R01 1HL134840-01/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Norway ; Male ; *Reproductive Techniques, Assisted ; *Fertility/genetics ; Adult ; Cohort Studies ; *Telomere/genetics ; Infertility/genetics ; },
abstract = {BACKGROUND: Telomere length (TL) has been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, with some studies finding associations with shorter TL and others with longer TL. In men, studies mostly report associations between shorter TL and sperm quality. To our knowledge, no studies have thus far investigated associations between TL and fecundability or the use of assisted reproductive technologies (ART).

METHODS: This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated associations between leukocyte TL (LTL) and fecundability (defined as the probability to conceive within a given menstrual cycle), infertility (defined has having spent 12 months or more trying to conceive without success), and ART use. We also repeated the analyses using instrumental variables for LTL consisting of genetic risk scores for LTL and genetically predicted LTL.

RESULTS: Approximately 11% of couples had experienced infertility and 4% had used ART. LTL was not associated with fecundability in women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility in women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing LTL in men (OR, 1.22; CI, 1.03-1.46), but not in women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables for LTL.

CONCLUSIONS: We found no indication that LTL is a suitable biomarker for assessing fecundability, infertility, or ART use. Additional studies are required to replicate the association observed between LTL and ART use in men.},
}

Humans
Female
Norway
Male
*Reproductive Techniques, Assisted
*Fertility/genetics
Adult
Cohort Studies
*Telomere/genetics
Infertility/genetics

@article {pmid39695460,
year = {2024},
author = {Eren Ozdemir, A},
title = {Evaluation of the effect of melatonin treatment on telomere length of the retinal pigment epithelium in streptozotocin-induced diabetic rat model.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {532},
pmid = {39695460},
issn = {1471-2415},
mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Diabetes Mellitus, Experimental/drug therapy ; *Rats, Sprague-Dawley ; Male ; *Retinal Pigment Epithelium/drug effects/pathology ; *Diabetic Retinopathy/drug therapy ; Rats ; Telomere/drug effects ; Antioxidants/pharmacology ; Streptozocin ; },
abstract = {OBJECTIVES: We aimed to investigate the effect of diabetic retinopathy and melatonin treatment on the relative telomer lengths (RTL) in retinal pigment epithelium (RPE) cells in a streptozotocin-induced diabetic rat model.

BACKGROUND: TL can be used to evaluate diabetes mellitus, its complications, and the effectiveness of its treatment. However, TL assessment has not been performed in retinal cells in a diabetic retinopathy model until now.

METHODS: Forty Sprague-Dawley male rats were randomly divided into four groups. The experimental groups were: Control Group (C): non- diabetic rats; Diabetes Mellitus Group (DM): rats induced to diabetes without treatment; Melatonin and Diabetes Mellitus Group (Mel + DM): rats induced to diabetes and after confirmation, treated with melatonin; Melatonin Group (Mel): rats were not induced to diabetes, treated with melatonin. Diabetes was induced by intraperitoneal administration of streptozotocin solution after 12 h food fasting. For eight weeks after the diabetes was induced, melatonin was administered via subcutaneous injection at a dose of 10 mg / kg. RTLs were measured by qPCR method with modifications. The comparison of averaged data among groups was performed using least significant difference (LSD) and Kruskal - Wallis Test and One way ANOVA test.

RESULTS: RTL was significantly similar in control and melatonin group. RTL was thinnest in DM group, in addition melatonin treatment significantly prevented the RTL shortening in DM + Mel group (p = 0.031).

CONCLUSION: We demonstrated that diabetic retinopathy led to the shortening of RTL in RPE cells in rats and melatonin treatment prevents this shortening.},
}

Animals
*Melatonin/pharmacology/therapeutic use
*Diabetes Mellitus, Experimental/drug therapy
*Rats, Sprague-Dawley
Male
*Retinal Pigment Epithelium/drug effects/pathology
*Diabetic Retinopathy/drug therapy
Rats
Telomere/drug effects
Antioxidants/pharmacology
Streptozocin

@article {pmid39695221,
year = {2024},
author = {Wang, B and Zhang, R and Sun, W and Yang, J},
title = {A nearly telomere-to-telomere diploid genome assembly of Firmiana kwangsiensis, a threatened species in China.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1394},
pmid = {39695221},
issn = {2052-4463},
mesh = {*Endangered Species ; *Telomere/genetics ; China ; *Haplotypes ; *Genome, Plant ; Diploidy ; },
abstract = {Firmiana kwangsiensis is a tree species of high ornamental value. The species is critically endangered in the wild, and is listed as a first-class national protected wild plant in China, and a Plant Species with Extremely Small Populations in need of urgent protection. We have assembled a chromosome-scale, haplotype-resolved genome for F. kwangsiensis using a combination of PacBio HiFi sequencing, ONT sequencing, and Hi-C sequencing. The final assembled genome is 2.3 G in size and comprises 2n = 40 chromosomes. All chromosomal ends contain telomeric characteristic motifs (TTTAGGG), and there are only 2 gaps within the rDNA regions, both close to a T2T genome assembly. Two complete sets of haplotypes are present, Haplotype A (1169.19 Mb) and Haplotype B (1157.87 Mb), with contig N50 lengths of 58.37 Mb and 57.27 Mb, respectively. The genome contains a total of 67,527 coding genes, with 62,351 genes functionally annotated here. This is the first report of the genome of F. kwangsiensis, and lays the foundation for future conservation genomics research into this species.},
}

*Endangered Species
*Telomere/genetics
China
*Haplotypes
*Genome, Plant
Diploidy

@article {pmid39695150,
year = {2024},
author = {Zhou, Q and Liu, X and Song, Y and Li, M and Fan, G and Chen, S},
title = {Telomere-to-telomere gapless genome assembly of the giant grouper (Epinephelus lanceolatus).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1342},
pmid = {39695150},
issn = {2052-4463},
mesh = {Animals ; *Genome ; *Telomere/genetics ; Bass/genetics ; Chromosomes ; },
abstract = {The giant grouper (Epinephelus lanceolatus) is a large coral reef fish distributed in the Indian Ocean and the Pacific Ocean. With a high market value, this species can grow up to approximately 2.7 meters in length and weigh 440 kilograms. With the rapid development of bioinformatics, higher standards of genome analysis are now required compared to previous reference genomes. This study presents a gapless assembly of the giant grouper genome, which has a length of 1.03 Gb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (1.02 Gb), and telomeres were detected on 24 chromosomes. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 59.24. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study inferred 25,815 protein-coding genes. These results lay a foundation for exploring the evolution and biology of the giant grouper, and advancing molecular breeding techniques.},
}

Animals
*Genome
*Telomere/genetics
Bass/genetics
Chromosomes

@article {pmid39694814,
year = {2024},
author = {Cacchione, S and Cenci, G and Dion-Côté, AM and Barbash, DA and Raffa, GD},
title = {Maintaining Telomeres without Telomerase in Drosophila: Novel Mechanisms and Rapid Evolution to Save a Genus.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041708},
pmid = {39694814},
issn = {1943-0264},
abstract = {Telomere maintenance is crucial for preventing the linear eukaryotic chromosome ends from being mistaken for DNA double-strand breaks, thereby avoiding chromosome fusions and the loss of genetic material. Unlike most eukaryotes that use telomerase for telomere maintenance, Drosophila relies on retrotransposable elements-specifically HeT-A, TAHRE, and TART (collectively referred to as HTT)-which are regulated and precisely targeted to chromosome ends. Drosophila telomere protection is mediated by a set of fast-evolving proteins, termed terminin, which bind to chromosome termini without sequence specificity, balancing DNA damage response factors to avoid erroneous repair mechanisms. This unique telomere capping mechanism highlights an alternative evolutionary strategy to compensate for telomerase loss. The modulation of recombination and transcription at Drosophila telomeres offers insights into the diverse mechanisms of telomere maintenance. Recent studies at the population level have begun to reveal the architecture of telomere arrays, the diversity among the HTT subfamilies, and their relative frequencies, aiming to understand whether and how these elements have evolved to reach an equilibrium with the host and to resolve genetic conflicts. Further studies may shed light on the complex relationships between telomere transcription, recombination, and maintenance, underscoring the adaptive plasticity of telomeric complexes across eukaryotes.},
}

@article {pmid39694812,
year = {2024},
author = {Markiewicz-Potoczny, M and Denchi, EL},
title = {Telomere Protection in Stem Cells.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041686},
pmid = {39694812},
issn = {1943-0264},
abstract = {The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells. In this review, we discuss what is known about the differences between stem cells and somatic cells regarding chromosome end protection.},
}

@article {pmid39694813,
year = {2024},
author = {Ferreira, MG},
title = {Telomere Dynamics in Zebrafish Aging and Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041696},
pmid = {39694813},
issn = {1943-0264},
abstract = {Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.},
}

@article {pmid39693631,
year = {2024},
author = {Su, R and Zhou, H and Yang, W and Moqir, S and Ritu, X and Liu, L and Shi, Y and Dong, A and Bayier, M and Letu, Y and Manxi, X and Chulu, H and Nasenochir, N and Meng, H and Herrid, M},
title = {Near telomere-to-telomere genome assembly of Mongolian cattle: implications for population genetic variation and beef quality.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae099},
pmid = {39693631},
issn = {2047-217X},
support = {//Department of Science and Technology/ ; 2022JBGS0023//Inner Mongolia Autonomous Region/ ; },
mesh = {Animals ; Cattle/genetics ; *Telomere/genetics ; *Genetic Variation ; *Genome ; Molecular Sequence Annotation ; Red Meat/standards ; Genetics, Population ; Whole Genome Sequencing/methods ; Male ; Genomics/methods ; },
abstract = {BACKGROUND: Mongolian cattle, a unique breed indigenous to China, represent valuable genetic resources and serve as important sources of meat and milk. However, there is a lack of high-quality genomes in cattle, which limits biological research and breeding improvement.

FINDINGS: In this study, we conducted whole-genome sequencing on a Mongolian bull. This effort yielded a 3.1 Gb Mongolian cattle genome sequence, with a BUSCO integrity assessment of 95.9%. The assembly achieved both contig N50 and scaffold N50 values of 110.9 Mb, with only 3 gaps identified across the entire genome. Additionally, we successfully assembled the Y chromosome among the 31 chromosomes. Notably, 3 chromosomes were identified as having telomeres at both ends. The annotation data include 54.31% repetitive sequences and 29,794 coding genes. Furthermore, a population genetic variation analysis was conducted on 332 individuals from 56 breeds, through which we identified variant loci and potentially discovered genes associated with the formation of marbling patterns in beef, predominantly located on chromosome 12.

CONCLUSIONS: This study produced a genome with high continuity, completeness, and accuracy, marking the first assembly and annotation of a near telomere-to-telomere genome in cattle. Based on this, we generated a variant database comprising 332 individuals. The assembly of the genome and the analysis of population variants provide significant insights into cattle evolution and enhance our understanding of breeding selection.},
}

Animals
Cattle/genetics
*Telomere/genetics
*Genetic Variation
*Genome
Molecular Sequence Annotation
Red Meat/standards
Genetics, Population
Whole Genome Sequencing/methods
Male
Genomics/methods

@article {pmid39693366,
year = {2024},
author = {Sato, MP and Arafa, RA and Rakha, M and Emeran, AA and Isobe, S and Shirasawa, K},
title = {Near-complete telomere-to-telomere de novo genome assembly in Egyptian clover (Trifolium alexandrinum).},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {},
number = {},
pages = {},
doi = {10.1093/dnares/dsae036},
pmid = {39693366},
issn = {1756-1663},
abstract = {Egyptian clover (Trifolium alexandrinum L.), also known as berseem clover, is an important forage crop to Semi-arid conditions that was domesticated in ancient Egypt since 6,000 years BC and introduced and well adapted to numerous countries including India, Pakistan, Turkey, and Mediterranean region. Despite its agricultural importance, genomic research on Egyptian clover has been limited to developing efficient modern breeding programs. In the present study, we constructed near-complete telomere-to-telomere-level genome assemblies for two Egyptian clover cultivars, Helaly and Fahl. Initial assemblies were established by using highly-fidelity long-read technology. To extend sequence contiguity, we developed a gap-targeted sequencing (GAP-Seq) method, in which contig ends are targeted for sequencing to obtain long reads bridging two contigs. The total length of the resultant chromosome-level assemblies was 547.7 Mb for Helaly and 536.3 Mb for Fahl. These differences in sequence length can be attributed to the expansion of DNA transposons. Population genomic analysis using single-nucleotide polymorphisms revealed genomic regions highly differentiated between two cultivars and increased genetic uniformity within each cultivar. Gene ontologies associated with metabolic and biosynthetic processes and developmental processes were enriched in these genomic regions, indicating that these genes may determine the unique characteristics of each cultivar. Comprehensive genomic resources can provide valuable insights into genetic improvements in Egyptian clover and legume genomics.},
}

@article {pmid39692822,
year = {2024},
author = {Zhou, K and Liu, X and Wang, M and Duan, J and Zhao, X and Yin, H},
title = {The landscape in telomere related gene prognostic signature for survival and medication treatment effectiveness prediction in hepatocellular carcinoma.},
journal = {Discover oncology},
volume = {15},
number = {1},
pages = {765},
pmid = {39692822},
issn = {2730-6011},
abstract = {OBJECTIVE: Telomeres, made of repetitive DNA sequences and shelterin complexes, which were found at the ends of chromosomes and had been extensively studied in cancer research. However, in hepatocellular carcinoma (HCC) was still relatively scarce. In this study, we investigated the correlation between telomerase-related genes (TRGs) and the prognosis and immunotherapy of HCC patients to enhance clinical outcomes.

METHODS: In this work, TRGs were gathered using TelNet, while clinical information and gene expression data for HCC patients were retrieved from the Cancer Genome Atlas (TCGA) database. A risk prediction model based on TRGs was created using COX and Lasso regression analyses, with ROC curves used to assess prognostic efficacy. Univariate and multifactorial COX regression analyses were used to determine if the risk model had an independent impact on prognosis. Nomograms were created to enhance clinical usability, and calibration curves were used to assess predictive ability at various time points. The Tumor Immune Dysfunction and Exclusion (TIDE) score was used to analyze differences in immune infiltrating cells between risk groups. The study analyzed the relationship between risk ratings and drug treatment effectiveness using data from the CellMiner database. The hub gene was identified and its relationship to prognostic markers of HCC patients was examined. The expression of hub genes in immune cell subpopulations was also investigated by single-cell data.

RESULTS: 2093 TRGs were identified, with 949 showing significant differences in expression between HCC and paracancerous tissues. Seven risk genes were overexpressed in tumor tissues, leading to lower survival rates in high-risk patients. Risk model could independently predict the prognosis of HCC patients. Analysis of tumor immune infiltrating cells revealed significant differences in cell abundance between risk groups, with notable variations in immune subset enrichment between subgroups. Higher risk scores correlated with increased sensitivity to sorafenib, mitoxantrone, oxaliplatin, gemcitabine, and entinostat, while sensitivity decreased for vincristine, etc. CDCA8 was identified as a key gene in the Protein Interaction Network, while high expression associated with poorer overall survival, tumor proliferation and metastasis. The results of single-cell data analysis suggest that CDCA8 may promote the development of HCC by affecting T lymphocytes.

CONCLUSION: The TRG-based risk model could predict HCC patient prognosis and closely linked to tumor immune environment, which could offer new possibilities for clinical treatment.},
}

@article {pmid39689933,
year = {2024},
author = {van Duijvenboden, S and Nelson, CP and Raisi-Estabragh, Z and Ramirez, J and Orini, M and Wang, Q and Aung, N and Codd, V and Stoma, S and Allara, E and Wood, AM and Di Angelantonio, E and Danesh, J and Harvey, NC and Petersen, SE and Munroe, PB and Samani, NJ},
title = {Leucocyte telomere length and conduction system ageing.},
journal = {Heart (British Cardiac Society)},
volume = {},
number = {},
pages = {},
doi = {10.1136/heartjnl-2024-324875},
pmid = {39689933},
issn = {1468-201X},
abstract = {BACKGROUND: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.

METHODS: In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59 868 and 62 266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420 071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR).

RESULTS: Mean PR interval and QRS duration were 144.2 ms (± 20.4) and 92.3 ms (± 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95% CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered.

CONCLUSIONS: Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age.},
}

@article {pmid39689244,
year = {2024},
author = {Pickler, RH and Ford, JL and Tan, A and Browning, C and Tarrence, J and Kertes, DA},
title = {Childhood Adversity and Telomere Length.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004241309368},
doi = {10.1177/10998004241309368},
pmid = {39689244},
issn = {1552-4175},
abstract = {Purpose: Exposure to adversity during childhood and adolescence is associated with numerous health conditions in adulthood; telomere shortening may be a mechanism through which adversity contributes to poor outcomes. We studied three areas of adversity (parent relational instability, child household instability, and financial instability) occurring during three epochs across childhood and adolescence and their associations with telomere length during adolescence. Methods: Data were obtained from the first wave of a longitudinal cohort study of youth aged 11-17 and their primary caregiver. Caregivers completed demographic and adversity questionnaires; youth provided a saliva sample for DNA extraction for telomere analysis. Results: Of 879 youth, over half experienced some adversity. More than one third experienced parent relational instability in each age epoch, with nearly a quarter experiencing parent relational instability in all age epochs. Youth experienced a similar pattern of financial instability but lower rates of child household instability. Youth experiencing parent relational instability at two or three epochs had shorter telomeres compared to those without any parent relational instability (p < .004). Youth who experienced child household instability in two age epochs had shorter telomeres (p = .003) and youth who experienced financial instability across all three epochs had shorter telomeres (p = .013) compared to youth without these adversities. Conclusion: Continuing exposure to adversity in early childhood may be more likely to affect telomere length. Research is needed to further determine adversities exerting the most effect and to understand if early telomere shortening has long term health effects.},
}

@article {pmid39688874,
year = {2024},
author = {Olsson, M and Miller, E and Rollings, N and Lillie, M and Hufton, J and Hansson, A and Wapstra, E},
title = {The effects of costly telomere maintenance on lifespan - reproductive tradeoffs in sand lizards.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpae181},
pmid = {39688874},
issn = {1558-5646},
abstract = {Telomeres are DNA-protein structures that primarily protect chromosomes and serve multiple functions of gene regulation. When cells divide, telomeres shorten and their main repair system in ectotherms - telomerase - replaces lost nucleotide complexes ((T2AG3)n in vertebrates). It remains a challenge to experimentally investigate resource requirements for telomere maintenance and its effects on lifespan-reproductive tradeoffs in the wild. In sand lizards (Lacerta agilis), we show that higher female investments into reproduction results in corresponding shortening of telomeres and that males have less frequent and less profound telomere shortening than females; a contributing factor to this may be males' higher telomerase levels. To manipulate resource access for telomere maintenance, we exploit a pseudo-experimental opportunity to analyze 'onboard' resources long-term using lizards that drop their tails with fat and nutrient deposits when attacked by predators. Females with less resources due to regrown tails less often and less profoundly elongate telomeres. Adult lizards with the most TL elongation live the longest, females with the highest lifetime reproductive success shorten telomeres the most, whereas males with the most telomere elongation have the highest lifetime reproductive success. This suggests ongoing evolution of resource-constrained telomere maintenance.},
}

@article {pmid39681615,
year = {2024},
author = {Weisert, N and Majewski, V and Hartleb, L and Luko, K and Lototska, L and Krapoth, NC and Ulrich, HD and Janzen, CJ and Butter, F},
title = {TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30493},
pmid = {39681615},
issn = {2045-2322},
mesh = {*Trypanosoma brucei brucei/genetics/metabolism ; *Telomere/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Variant Surface Glycoproteins, Trypanosoma/genetics/metabolism ; Protein Binding ; Proteomics/methods ; },
abstract = {The extracellular parasite Trypanosoma brucei evades the immune system of the mammalian host by periodically exchanging its variant surface glycoprotein (VSG) coat. Hereby, only one VSG gene is transcribed from one of 15 subtelomeric so-called bloodstream form expression sites (BES) at any given timepoint, while all other BESs are silenced. VSG gene expression is altered by homologous recombination using a large VSG gene repertoire or by a so-called in situ switch, which activates a previously silent BES. Transcriptional activation, VSG switching and VSG silencing during developmental differentiation from the bloodstream form to the procyclic form present in the tsetse fly vector are tightly regulated. Due to their subtelomeric position, telomere-associated proteins are involved in the regulation of VSG expression. Three functional homologs of mammalian telomere complex proteins have been characterized thus far, and novel telomere-interacting proteins, such as telomere-associated protein 1 (TelAP1), have recently been identified. Here, we used mass spectrometry-based proteomics and interactomics approaches, telomere pull-down assays with recombinant material and immunofluorescence analysis to elucidate the interactions of 21 other putative TelAPs. We investigated the influence on VSG expression and showed that depletion of TelAPs does not ultimately lead to changes in VSG expression. Additionally, we examined the interaction patterns of four TelAPs with the TbTRF/TbTIF2/TbRAP1 telomere complex by reciprocal affinity purification. We further propose that TelAP1 interacts with Tb927.6.4330, now called TelAP2, and that TelAP1 depends on this interaction to form a complex with the telomeric proteins TbTRF, TbTIF2 and TbRAP1.},
}

*Trypanosoma brucei brucei/genetics/metabolism
*Telomere/metabolism/genetics
*Protozoan Proteins/metabolism/genetics
Telomere-Binding Proteins/metabolism/genetics
Variant Surface Glycoproteins, Trypanosoma/genetics/metabolism
Protein Binding
Proteomics/methods

@article {pmid39680438,
year = {2024},
author = {Pearce, EE and Majid, A and Brown, T and Shepherd, RF and Rising, C and Wilsnack, C and Thompson, AS and Gilkey, MB and Ribisl, KM and Lazard, AJ and Han, PK and Werner-Lin, A and Hutson, SP and Savage, SA},
title = {"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.},
journal = {JMIR formative research},
volume = {8},
number = {},
pages = {e64343},
doi = {10.2196/64343},
pmid = {39680438},
issn = {2561-326X},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Aged ; *Qualitative Research ; *Internet ; *Social Support ; Information Seeking Behavior ; Telomere/genetics ; Caregivers/psychology ; },
abstract = {BACKGROUND: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.

OBJECTIVE: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.

METHODS: Our qualitative descriptive study used semistructured interviews of patients with TBDs and caregivers. Data were transcribed verbatim and thematically analyzed by an interdisciplinary team.

RESULTS: A total of 32 adults completed interviews. Participant ages ranged from 27 to 74 years. The majority (n=28, 88%) were female, occupied multiple TBD roles (eg, patient and parent), and had undergone genetic testing. Most engaged in web-based information-seeking (n=29, 91%) and TBD-specific social media (n=26, 81%). Participants found web-based resources useful for information-seeking but reported privacy concerns and frustration with forming supportive relationships. Most participants described ambivalence toward web-based resource use, citing tensions between hunger for information versus distrust, empowerment versus overwhelm, disclosure versus privacy, and accessibility versus connection. Fluctuations in web-based support use arose from perceived harms, information saturation, or decreased relevance over the course of TBD illness experience.

CONCLUSIONS: Individuals with TBDs and their caregivers reported frequent use of web-based informational and emotional support. However, ambivalence about the benefits and liabilities of web-based resources and persistent medical uncertainty may impact the adoption of and adherence to web-based support among patients with TBD and caregivers. Our findings suggest web-based psychosocial support should target long-term and multifaceted informational and emotional needs, be user-initiated, be offered alongside in-person formats, provide expert-informed information, and be attentive to personal privacy and evolving support needs of the TBD community. This study suggests web-based resources will be most effective in the TBD context when they achieve the following features: (1) offer a variety of ways to engage (eg, active and passive), (2) provide privacy protections in moderated "safe spaces" designed for personal disclosure, (3) offer separate venues for informational versus emotional support, (4) combine web-based relationship formation with opportunities for in-person gathering, (5) provide information that is reliable, easy to access, and informed by medical professionals, (6) remain mindful of user distress, and (7) are responsive to variations in levels and types of engagement. Additionally, advocacy organizations may wish to avoid traditional social media platforms when designing safe spaces for web-based emotional support, instead pivoting to internet-based tools that minimize privacy threats and limit the perpetual public availability of shared information.},
}

Humans
Female
Male
Middle Aged
Adult
Aged
*Qualitative Research
*Internet
*Social Support
Information Seeking Behavior
Telomere/genetics
Caregivers/psychology

@article {pmid39675625,
year = {2024},
author = {Xie, JW and Wang, HL and Lin, LQ and Guo, YF and Wang, M and Zhu, XZ and Niu, JJ and Lin, LR},
title = {Telomere-Methylation Genes: Novel Prognostic Biomarkers for Hepatocellular Carcinoma.},
journal = {Clinics and research in hepatology and gastroenterology},
volume = {},
number = {},
pages = {102516},
doi = {10.1016/j.clinre.2024.102516},
pmid = {39675625},
issn = {2210-741X},
abstract = {BACKGROUND: Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.

METHOD: This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.

RESULT: The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.

CONCLUSION: This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.},
}

@article {pmid39667908,
year = {2024},
author = {Jung, JH and Byun, MS and Yi, D and Ahn, H and Lee, JH and Lee, JS and Lee, HS and Lee, JY and Kim, YK and Lee, YS and Kang, KM and Sohn, CH and Lee, DY and , },
title = {Telomere length, in vivo Alzheimer's disease pathologies and cognitive decline in older adults.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2024-334314},
pmid = {39667908},
issn = {1468-330X},
abstract = {BACKGROUND: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults.

METHODS: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years.

RESULTS: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group.

CONCLUSION: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations.},
}

@article {pmid39665795,
year = {2024},
author = {Ying, C and Han, C and Li, Y and Zhang, M and Xiao, S and Zhao, L and Zhang, H and Yu, Q and An, J and Mao, W and Cai, Y},
title = {Plasma circulating cell-free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy: a cross-sectional study.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-00599},
pmid = {39665795},
issn = {1673-5374},
abstract = {In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell-free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson's disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson's disease (stage 1-2 of Hoehn & Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls (P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter (P = 0.003 for Parkinson's disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson's disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54-24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55-122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease (OR: 0.16; 95% CI: 0.04-0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01-0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.},
}

@article {pmid39664691,
year = {2024},
author = {Wang, J and Xu, D and Sang, YL and Sun, M and Liu, C and Niu, M and Li, Y and Liu, L and Han, X and Li, J},
title = {A telomere-to-telomere gap-free reference genome of Chionanthus retusus provides insights into the molecular mechanism underlying petal shape changes.},
journal = {Horticulture research},
volume = {11},
number = {12},
pages = {uhae249},
pmid = {39664691},
issn = {2662-6810},
abstract = {Chionanthus retusus, an arbor tree of the Oleaceae family, is an ecologically and economically valuable ornamental plant for its remarkable adaptability in landscaping. During C. retusus breeding, we observed diverse floral shapes; however, no available genome for C. retusus has hindered the widespread identification of genes related to flower morphology. Thus, a de novo telomere-to-telomere (T2T) gap-free genome was generated. The assembly, incorporating high-coverage and long-read sequencing data, successfully yielded two complete haplotypes (687 and 683 Mb). The genome encompasses 42 864 predicted protein-coding genes, with all 46 telomeres and 23 centromeres in one haplotype. Whole-genome duplication analysis revealed that C. retusus underwent one fewer event of whole-genome duplication after differentiation compared to other species in the Oleaceae family. Furthermore, flower vein diversity was the main reason for the differences in floral shapes. Auxin-related genes were responsible for petal shape formation on genome-based transcriptome analysis. Specifically, the removal and retention of the first intron in CrAUX/IAA20 resulted in the production of two transcripts, and the differences in the expression levels of CrAUX/IAA20 resulted in the variations of flower veins. Compared to transcripts lacking the first intron, transcripts with intron retention caused more severe decreases in the number and length of flower veins in transgenic Arabidopsis thaliana. Our findings will deepen our understanding of flower morphology development and provide important theoretical support for the cultivation of Oleaceae.},
}

@article {pmid39662066,
year = {2024},
author = {Fragkiadaki, P and Apetroaei, MM and Kouvidi, E and Vakonaki, E and Renieri, E and Fragkiadoulaki, I and Spanakis, M and Baliou, S and Alegakis, A and Tsatsakis, A},
title = {The association between short telomere length and cardiovascular disease.},
journal = {Cytogenetic and genome research},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000542795},
pmid = {39662066},
issn = {1424-859X},
abstract = {INTRODUCTION: Telomeres, repetitive DNA sequences at chromosome ends, shorten with cell division, countered by telomerase. Short telomeres are linked to cardiovascular disease (CVD), alongside its risk factors like aging, hypertension, diabetes, obesity, inactivity, and smoking. Many studies have claimed the implication of TL in cardiac diseases. This study examines telomere length's (TL) impact on heart conditions using quantitative fluorescence in situ hybridization (Q-FISH) technology.

METHODS: Thirteen CVD patients (nine men and four women) aged 30 to 70 years and aged-matched healthy participants from BIOTEL population TL database, were included in the study. Each chromosome's TL from peripheral blood cells (PBCs) was measured using metaphase Q-FISH. An independent samples t-test was used to compare participants' mean or median TL with various medical factors and habits Results: The mean TL of whole and short telomeres in cardiac disease patients was lower compared to aged-matched healthy controls; however, there was no statistical significance due to the limited patient sample. The mean TL of short telomeres in cardiac disease patients showed a remarkable decline with advanced age. Accordingly, the mean TL of whole and short telomeres in patients with cardiac diseases showed a similar reduced trend.

CONCLUSION: In our study, shorter TL was observed in cardiac disease patients compared to those of healthy controls by using metaphase Q-FISH. However, more cases need to be studied to elucidate the use of TL as a potential biomarker for the diagnosis of patients with CVD.},
}

@article {pmid39661724,
year = {2024},
author = {Peng, D and Hong, Z and Kan, S and Wu, Z and Liao, X},
title = {The telomere-to-telomere (T2T) genome provides insights into the evolution of specialized centromere sequences in sandalwood.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae096},
pmid = {39661724},
issn = {2047-217X},
support = {2021QN02N792//Guangdong Provincial Pearl River Talents Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; },
mesh = {*Centromere/genetics ; *Telomere/genetics ; *Genome, Plant ; *Evolution, Molecular ; Chromosomes, Plant ; Genomics/methods ; },
abstract = {BACKGROUND: Sandalwood, a prized hemiparasitic plant, is highly sought in the commercial market because of its aromatic core materia. The structure and stability of the genome are instrumental in the rapid adaptation of parasitic plants to their surroundings. However, there is a conspicuous lack of research on the genomic-level adaptive evolution of sandalwood.

RESULTS: In this study, we assembled a gap-free telomere-to-telomere (T2T) reference genome for Santalum album using PacBio HiFi, Hi-C, and ultra-long ONT data. The T2T reference genome (Sal_t2t) encompassed annotations of 24,171 genes and 25.34% repetitive sequences, in addition to all 10 centromeres and 20 telomeres across the 10 chromosomes. The results revealed that the 3 distinct parasitic species of Santalales had diverse centromeric compositions. The Copia-type long terminal repeat transposon emerged as the most significant in the S. album genome, constituting the primary sequence of the centromere and influencing gene expression. Third, in sandalwood, the presence of Copia affected the size of the centromeres and, consequently, the genome size. Identification of the sandalwood T2T genome in this study also enabled the identification of more precise organelle transfer fragments.

CONCLUSIONS: Our research provides a sandalwood T2T genome, laying the groundwork for future investigations on the evolution of energy organs in parasitic plants. Moreover, it offers novel insights into the function and evolution of centromeres, as well as the mechanisms of adaptation and parasitism.},
}

*Centromere/genetics
*Telomere/genetics
*Genome, Plant
*Evolution, Molecular
Chromosomes, Plant
Genomics/methods

@article {pmid39661387,
year = {2024},
author = {Niewisch, MR and Kim, J and Giri, N and Lunger, JC and McReynolds, LJ and Savage, SA},
title = {Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders.},
journal = {JAMA network open},
volume = {7},
number = {12},
pages = {e2450111},
doi = {10.1001/jamanetworkopen.2024.50111},
pmid = {39661387},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; Adult ; *Neoplasms/genetics/epidemiology ; Longitudinal Studies ; Middle Aged ; Genotype ; Telomere/genetics ; Aged ; Risk Factors ; Genetic Predisposition to Disease ; Bone Marrow Failure Disorders/genetics ; Incidence ; Young Adult ; Adolescent ; },
abstract = {IMPORTANCE: Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance.

OBJECTIVE: To quantify cancer risks in TBDs by genetic subgroups.

This longitudinal cohort study of TBDs assessed cancer occurrences from 2002 through 2022. Participants were individuals with a TBD-associated pathogenic germline variant recruited across institutions by self-referral. Data were collected and analyzed through June 30, 2022.

EXPOSURES: The exposure was TBD genotypes, with subgroups defined by inheritance pattern (autosomal-dominant [AD-non-TINF2] vs autosomal-recessive/X-linked [AR/XLR] vs AD-TINF2).

MAIN OUTCOMES AND MEASURES: The main outcome was cancer; secondary outcomes included death, or organ transplant. Cumulative cancer incidence was determined considering death or transplant as competing events. Observed:expected (O:E) ratios of cancer before and after any organ transplant were calculated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.

RESULTS: Among 230 individuals with TBD (135 [58.7%] male; median [range] age at last follow-up, 34.6 [1.4-82.2] years) included, the risk of cancer was 3-fold higher than the general population (O:E, 3.35 [95% CI, 2.32-4.68]). The highest risk was observed in individuals with AR/XLR (O:E, 19.16 [95% CI, 9.19-35.24]) with a significantly younger cancer onset than in individuals with AD-non-TINF2 (median [range] age, 36.7 [25.2-53.6] years vs 44.5 [32.2-67.5] years; P = .01). The risk of solid tumors was highest in individuals with AR/XLR (O:E = 23.97 [95% CI, 10.96-45.50]), predominantly head and neck squamous cell carcinomas (O:E, 276.00 [95% CI, 75.20-706.67]). Hematologic malignant neoplasm risk was highest in individuals with AD-non-TINF2 (O:E, 9.41 [95% CI, 4.30-17.86]). Solid tumor cumulative incidence increased to 12% for individuals with AR/XLR by age 45 years and to 13% for individuals with AD-non-TINF2 by age 70 years. The cumulative incidence of hematologic malignant neoplasms leveled off at 2% by age 30 years and 19% by age 70 years in individuals with AR/XLR and AD-non-TINF2, respectively. Individuals with AD-TINF2 showed the highest cumulative incidence for transplant or death (49% by age 15 years). Following transplant, individuals with AR/XLR (O:E, 136.11 [95% CI, 54.72-280.44) or AD-TINF2 (O:E, 81.07 [95% CI, 16.72-236.92]) had the highest cancer risk, predominantly young-onset head and neck squamous cell carcinomas (median [range] age, 32.2 [10.5-35.5] years).

CONCLUSIONS AND RELEVANCE: This cohort study of individuals with TBDs found an increased cancer risk compared with the general population, with the earliest age at onset for individuals with AR/XLR inheritance. Cancer risks increased after organ transplant across all subgroups. These differences in TBD-associated cancer risks by mode of inheritance suggest cancer screening could be tailored by genotype, but additional research is warranted.},
}

Humans
Male
Female
Adult
*Neoplasms/genetics/epidemiology
Longitudinal Studies
Middle Aged
Genotype
Telomere/genetics
Aged
Risk Factors
Genetic Predisposition to Disease
Bone Marrow Failure Disorders/genetics
Incidence
Young Adult
Adolescent

@article {pmid39658339,
year = {2024},
author = {Lame-Jouybari, AH and Fahami, MS and Hosseini, MS and Moradpour, M and Hojati, A and Abbasalizad-Farhangi, M},
title = {Association Between Maternal Prepregnancy and Pregnancy Body Mass Index and Children's Telomere Length: A Systematic Review and Meta-analysis.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuae187},
pmid = {39658339},
issn = {1753-4887},
support = {75731//Tabriz University of Medical Sciences/ ; },
abstract = {CONTEXT: Telomeres maintain chromosome stability and mark cellular aging, and their shortening with age compromises genomic stability.

OBJECTIVE: The purpose of this study was to conduct a meta-analysis of existing evidence to evaluate the relationship between the maternal pregnancy body mass index (BMI) and children's telomere length (TL).

DATA SOURCE: Web of Science, Scopus, and PubMed databases were systematically searched from their inception to August 27, 2023, for pertinent observational studies.

DATA EXTRACTION: The random-effects meta-analysis was conducted on eligible studies that investigated the linear relationship between exposure and the outcomes of interest, utilizing the reported β-coefficient. Cochran's Q test and I2 statistics were used to assess heterogeneity.

DATA ANALYSIS: A significant association was observed between maternal pregnancy BMI and children's TL (32 studies, pooled effect size [ES]: -0.04; 95% CI: -0.06 to -0.01; I2 = 47.51%, P < .001) and maternal prepregnancy BMI and children's TL at birth (16 studies; pooled ES: -0.05; 95% CI: -0.08 to -0.02; I2 = 53.49%, P < .001).

CONCLUSION: The findings indicate an inverse association between maternal prepregnancy BMI and TL in infants, which is evident within the normal to obese BMI range. This underscores the significance of maternal weight status before pregnancy as a determinant of offspring TL.

PROSPERO registration no. CRD42023466425.},
}

@article {pmid39653745,
year = {2024},
author = {Banu, S and Mk, K and George, JK and Siby, E and Bhagat, R and Ms, S and Patil, SJ and Phadke, SR and Sowpati, DT and Tallapaka, KB},
title = {Enhanced resolution of optical genome mapping utilizing telomere-to-telomere reference in genetic disorders.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39653745},
issn = {1476-5438},
abstract = {Reference genomes serve as a baseline criterion for comparison of personal genomes to deduce clinical variants. The widely used reference genome, GRCh38, contains stretches of gaps and unresolved bases particularly in complex regions which could obscure variant discovery. In contrast, the gapless telomere-to-telomere CHM13 (T2T-CHM13) reference genome can be used to assess difficult regions of the genome. Optical genome mapping (OGM), an imaging technique for structural variation identification has improved resolution compared to traditional cytogenetic methods. Our study showcases the utility of the T2T-CHM13 reference genome for enhanced structural variant (SV) detection in complex regions. We illustrate this through two clinical cases, where improved alignment with T2T-CHM13 led to significantly higher confidence scores for critical SVs. We demonstrate improved clinical diagnostic outcomes with the updated T2T-CHM13 reference and advocate its adoption.},
}

@article {pmid39652599,
year = {2024},
author = {Syed, S and Aloe, S and Sutherland, JH and Holloman, WK and Lue, NF},
title = {Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations.},
journal = {PLoS genetics},
volume = {20},
number = {12},
pages = {e1011515},
doi = {10.1371/journal.pgen.1011515},
pmid = {39652599},
issn = {1553-7404},
abstract = {TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungus Ustilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed that UmTrf2 binds to Blm in vitro and inhibits Blm-mediated unwinding of telomeric DNA substrates. Consistent with a similar inhibitory activity in vivo, over-expression of Trf2 induces telomere shortening, just like deletion of blm, which is required for efficient telomere replication. While the loss of Trf2 engenders growth arrest and multiple telomere aberrations, these defects are fully suppressed by the concurrent deletion of blm or mre11 (but not other DNA repair factors). Over-expression of Blm alone triggers aberrant telomere recombination and the accumulation of aberrant telomere structures, which are blocked by concurrent Trf2 over-expression. Together, these findings highlight the suppression of Blm as a key protective mechanism of Trf2. Notably, U. maydis harbors another double-strand telomere-binding protein (Tay1), which promotes Blm activity to ensure efficient replication. We found that deletion of tay1 partially suppresses the telomere aberration of Trf2-depleted cells. Our results thus point to opposing regulation of Blm helicase by telomere proteins as a strategy for optimizing both telomere maintenance and protection. We also show that aberrant transcription of both telomere G- and C-strand is a recurrent phenotype of telomere mutants, underscoring another potential similarity between double strand breaks and de-protected telomeres.},
}

@article {pmid39650708,
year = {2024},
author = {Wang, J and Xie, F and Zhu, W and Ye, D and Xiao, Y and Shi, M and Zeng, R and Bian, J and Xu, X and Chen, L and Zhu, A and Zhu, K and Fan, T and Liu, B and Xiao, L and Zhang, X},
title = {Relationship between serum carotenoids and telomere length in overweight or obese individuals.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1479994},
doi = {10.3389/fnut.2024.1479994},
pmid = {39650708},
issn = {2296-861X},
abstract = {BACKGROUND: Previous researches have demonstrated an association between carotenoids and elongated telomeres. Nonetheless, there is scant scientific evidence examining this relationship in individuals who are overweight or obese, a demographic more predisposed to accelerated aging. This study aims to elucidate the correlation between serum carotenoid concentrations and telomere length within this population group.

METHODS: Data were sourced from the 2001-2002 National Health and Nutrition Examination Survey, encompassing 2,353 overweight or obese participants. The levels of α-carotene, β-carotene (both trans and cis isomers), β-cryptoxanthin, lutein/zeaxanthin, and trans-lycopene were quantified via high-performance liquid chromatography. Telomere length was assessed using quantitative polymerase chain reaction.

RESULTS: Following adjustment for potential confounders, telomere length exhibited an increase of 1.83 base pairs (bp) per unit elevation in β-carotene levels (β = 1.83; 95% CI: 0.48, 3.18). Within the fully adjusted model, telomere length incremented by 1.7 bp per unit increase in serum β-carotene among overweight individuals (β = 1.7; 95% CI: 0.1, 3.3), and by 2.6 bp per unit increase among obese individuals (β = 2.6; 95% CI: 0.1, 5.0). Furthermore, restricted cubic spline analysis revealed a linear relationship between β-carotene levels and telomere length, whereas a non-linear association was observed between β-cryptoxanthin levels and telomere length.

CONCLUSION: This investigation indicates that higher serum β-carotene concentrations are linked with extended telomere length in overweight and obese populations in the United States. These findings warrant further validation through prospective studies.},
}

@article {pmid39647990,
year = {2024},
author = {Yang, H and Chen, L and Liu, Y},
title = {Association of leukocyte telomere length with the risk of digestive diseases: A large-scale cohort study.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {39647990},
issn = {2542-5641},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases.

METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity.

RESULTS: After a mean follow-up time of 11.8 years, over 20 the International Classification of Diseases 10th Revision (ICD-10) codes were observed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL.

CONCLUSIONS: This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.},
}

@article {pmid39647324,
year = {2024},
author = {Li, X and Wang, X and Yu, F and Li, Z and Chen, D and Qi, Y and Lu, Z and Liu, Y and Chen, D and Wu, Y},
title = {Development and validation of a prognostic and drug sensitivity model for gastric cancer utilizing telomere-related genes.},
journal = {Translational oncology},
volume = {52},
number = {},
pages = {102232},
doi = {10.1016/j.tranon.2024.102232},
pmid = {39647324},
issn = {1936-5233},
abstract = {BACKGROUND: Gastric cancer (GC) poses a major global health challenge because of its unfavorable prognosis. Elevated telomerase activity has been linked to the rapid growth and invasiveness of GC tumors. Investigating the expression profiles of telomerase could improve our understanding of the mechanisms underlying telomere-related GC advancement and its applicability as potential targets for diverse therapeutic strategies for GC.

METHODS: The TCGA and GEO databases were utilized to access transcriptome and clinical data related to GC. After assessing differentially expressed genes (DEGs), a prognostic risk model was developed through Cox univariate regression, LASSO-Cox regression. The prognostic risk model was validated using data from the GSE62254 cohort. The significant influence of the risk model on the tumor immune microenvironment (TIME) and its sensitivity to various drugs was assessed.

RESULTS: Differential expression analysis identified 328 significantly telomere-related DEGs in GC, with 35 of them showing a significant association with GC prognosis. A predictive risk model composed of four telomere-related genes (TRGs) was established, enabling the accurate stratification of GC patients into two distinct prognostic groups. The LASSO risk model demonstrated notable variations in immune-cell infiltration and drug sensitivity patterns between high- and low-risk groups.

CONCLUSIONS: The study establishes suggestive relationships between four TRGs (LRRN1, SNCG, GAMT, and PDE1B) and the prognosis of GC. The comprehensive characterization of the TRG model reveals their possible roles in the prognosis, TIME, and drug sensitivity in GC.},
}

@article {pmid39642730,
year = {2024},
author = {Li, R and Chen, G and Liao, W and Yuchi, Y and Yang, X and Zhang, Z and Liu, X and Mao, Z and Li, L and Zhao, J and Li, H and Huo, W and Guo, Y and Li, S and Wu, W and Wang, C and Hou, J},
title = {The role of telomere shortening in ambient ozone exposure-related insulin resistance.},
journal = {Journal of hazardous materials},
volume = {484},
number = {},
pages = {136768},
doi = {10.1016/j.jhazmat.2024.136768},
pmid = {39642730},
issn = {1873-3336},
abstract = {BACKGROUND: Ozone (O3) exposure and telomere shortening are associated with insulin resistance (IR). However, the role of telomere shortening in ambient O3 exposure-related IR is largely unclear.

METHODS: The Henan Rural Cohort recruited participants and performed a random forest method to estimate residential O3 concentration. IR was reflected by homeostasis model assessment-IR, quantitative insulin sensitivity check index, triglyceride and glucose index, etc. Generalized linear model, quantile regression model, and mediation effects analysis were utilized to assess the associations of O3 exposure and relative telomere length (RTL) with longitudinal IR markers and their change rates. Furthermore, the role of telomere homeostasis in O3-exposure-induced IR in vivo and in vitro experiments was verified.

RESULTS: O3 exposure was positively associated with longitudinal IR. The proportions of RTL mediated associations between O3 exposure and longitudinal IR markers ranged from 11.92 % to 60.36 %. O3-exposed mice exhibited a higher glucose load, upregulation of GSK-3β and G-6-Pase expression at mRNA levels, glycogen accumulation reduction, telomere shortening, and decreased telomerase reverse transcriptase activity relative to air-exposed mice. In vitro experiments reveal that overexpression of TERT in HepG2 cells up-regulated G-6-Pase mRNA expression level.

CONCLUSIONS: Impaired telomere homeostasis may be involved in O3 exposure-related IR via inhibition of glycogen synthesis and acceleration of gluconeogenesis and the specific mechanisms are still further elucidated.},
}

@article {pmid39639361,
year = {2024},
author = {Tan, L and Zhong, MM and Zhao, YQ and Feng, Y and Ye, Q and Hu, J and Ou-Yang, ZY and Chen, NX and Su, XL and Zhang, Q and Liu, Q and Yuan, H and Wang, MY and Feng, YZ and Guo, Y},
title = {The role of circulating polyunsaturated fatty acids in mediating the effect of BMI on leukocyte telomere length: analysis using Mendelian randomization.},
journal = {Nutrition & metabolism},
volume = {21},
number = {1},
pages = {104},
pmid = {39639361},
issn = {1743-7075},
support = {202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; },
abstract = {BACKGROUND: polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies.

METHODS: Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL.

RESULTS: None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: -0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: -0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p < 0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from β = -0.039 (95% CI: -0.058 to -0.020, p < 0.001) to -0.034 (95% CI: -0.054 to -0.014, p < 0.001).

CONCLUSIONS: This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL.},
}

@article {pmid39639031,
year = {2024},
author = {Dai, M and Li, K and Sacirovic, M and Zemmrich, C and Ritter, O and Bramlage, P and Persson, AB and Buschmann, E and Buschmann, I and Hillmeister, P},
title = {Cell-free plasma telomere length correlated with the risk of cardiovascular events using machine learning classifiers.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30390},
pmid = {39639031},
issn = {2045-2322},
mesh = {Humans ; *Machine Learning ; Male ; Female ; Middle Aged ; *Coronary Artery Disease/blood/diagnosis ; Retrospective Studies ; Aged ; *Heart Failure/blood/diagnosis ; Telomere ; Biomarkers/blood ; Telomere Homeostasis ; Risk Factors ; },
abstract = {This retrospective study explored the association between circulating cell-free plasma telomere length (cf-TL) and coronary artery disease (CAD) and heart failure (HF). Data from 518 participants were collected, including clinical and laboratory data. cf-TL was measured in plasma samples and machine learning (ML) classification models were developed to differentiate between CAD, HF and control conditions. Our results showed that cf-TL was significantly prolonged in HF patients compared to controls, but no significant difference was observed between CAD patients and controls. Additionally, cf-TL was significantly correlated with nitric oxide metabolites (NOx) and flow-mediated dilation (FMD), suggesting a potential link with endothelial function. To avoid data leakage and ensure the model captured only relationships relevant to the research question, we utilized a temporal data split, holding out the last year's data for testing (n = 81) and using the remaining data for training (n = 324) and validation (n = 109). The ML models using four variables achieved an area under the curve (AUC) of 0.795 in the validation dataset and 0.717 in the test dataset for CAD classification, and 0.829 in the validation dataset and 0.806 in the test dataset for HF classification. SHAP analysis revealed that cf-TL had minimal impact on the predictions of the CAD model, as indicated by consistently low SHAP values, whereas in the HF model, cf-TL exhibited a broader range of SHAP values, indicating a greater contribution to the model's classification. These findings suggest that cf-TL may play a more prominent role in HF pathophysiology and could serve as a valuable biomarker for predicting HF risk. Further studies are warranted to explore cf-TL's diagnostic and prognostic potential across different cardiovascular diseases.},
}

Humans
*Machine Learning
Male
Female
Middle Aged
*Coronary Artery Disease/blood/diagnosis
Retrospective Studies
Aged
*Heart Failure/blood/diagnosis
Telomere
Biomarkers/blood
Telomere Homeostasis
Risk Factors

@article {pmid39638969,
year = {2024},
author = {Sadr, Z and Ghasemi, M and Jafarpour, S and Seyfi, R and Ghasemi, A and Boustanipour, E and Khorshid, HRK and Ehtesham, N},
title = {Beginning at the ends: telomere and telomere-based cancer therapeutics.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {1},
pmid = {39638969},
issn = {1617-4623},
mesh = {Humans ; *Neoplasms/genetics/therapy/drug therapy ; *Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; *Telomere Homeostasis ; Animals ; },
abstract = {Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85-95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5-15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies.},
}

Humans
*Neoplasms/genetics/therapy/drug therapy
*Telomere/genetics/metabolism
*Telomerase/genetics/metabolism
*Telomere Homeostasis
Animals

@article {pmid39638831,
year = {2024},
author = {Zhu, N and Wang, X and Zhu, H and Zheng, Y},
title = {Exploring the role of alternative lengthening of telomere-related genes in diagnostic modeling for non-alcoholic fatty liver disease.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30309},
pmid = {39638831},
issn = {2045-2322},
mesh = {*Non-alcoholic Fatty Liver Disease/genetics/pathology/diagnosis/metabolism ; Animals ; Mice ; Humans ; Telomere Homeostasis/genetics ; Disease Models, Animal ; Gene Regulatory Networks ; Gene Expression Profiling ; Telomere/genetics/metabolism ; Prognosis ; },
abstract = {Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms.},
}

*Non-alcoholic Fatty Liver Disease/genetics/pathology/diagnosis/metabolism
Animals
Mice
Humans
Telomere Homeostasis/genetics
Disease Models, Animal
Gene Regulatory Networks
Gene Expression Profiling
Telomere/genetics/metabolism
Prognosis

@article {pmid39636971,
year = {2024},
author = {Liu, J and Li, Q and Hu, Y and Yu, Y and Zheng, K and Li, D and Qin, L and Yu, X},
title = {The complete telomere-to-telomere sequence of a mouse genome.},
journal = {Science (New York, N.Y.)},
volume = {386},
number = {6726},
pages = {1141-1146},
doi = {10.1126/science.adq8191},
pmid = {39636971},
issn = {1095-9203},
mesh = {Animals ; Mice ; *Telomere/genetics ; *Genome ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Mouse Embryonic Stem Cells ; Haploidy ; },
abstract = {The current reference genome of Mus musculus, GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.7% of previously uncovered sequences of the mouse genome, including ribosomal DNA arrays and pericentromeric and subtelomeric regions, as well as an additional 140 genes predicted to be protein-coding. This study helps to address knowledge gaps in the mouse genome.},
}

Animals
Mice
*Telomere/genetics
*Genome
Repetitive Sequences, Nucleic Acid
Sequence Analysis, DNA
Mouse Embryonic Stem Cells
Haploidy