@article {pmid41029149,
year = {2025},
author = {Feng, C and Zhong, S and Li, R and Lin, Y and Zhu, J and Liang, X and Xiao, C and Qin, C},
title = {Impact of smoking and alcohol consumption on telomere length: A univariable and multivariable Mendelian randomization study.},
journal = {Medicine},
volume = {104},
number = {39},
pages = {e44685},
doi = {10.1097/MD.0000000000044685},
pmid = {41029149},
issn = {1536-5964},
support = {Grant No.82060226//The National Natural Sciences Foundation of China/ ; GuikeAA22096030//The Guangxi Science and Technology Major Project/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Alcohol Drinking/genetics/adverse effects/epidemiology ; *Smoking/genetics/adverse effects/epidemiology ; *Telomere Shortening/genetics ; *Telomere/genetics ; Male ; },
abstract = {Telomere length is a potential biomarker for biological aging and is associated with many age-related pathologies. Although observational evidence has linked modifiable lifestyle factors to telomere attrition, the causal relationship between smoking, alcohol consumption, and telomere length remains controversial. This study aimed to investigate the causal effects of smoking and alcohol consumption on telomere length using Mendelian randomization (MR) analysis. Genetic data on smoking initiation (N = 805,431), alcohol consumption (N = 666,978), and telomere length (N = 472,174) were extracted from published summary statistics. Univariable and multivariable MR analyses were performed to comprehensively estimate the independent causal effects of smoking and alcohol consumption on telomere length. Cochran Q test and the MR Egger intercept test were used to detect heterogeneity and pleiotropy. A Steiger filtering test was conducted to confirm directional causal effects. Further sensitivity analyses were performed using the leave-one-out method and funnel plots. Inverse variance weighted (IVW) analysis showed that genetically predicted smoking initiation was significantly associated with shorter telomere length (univariable IVW: β = -0.08, 95% confidence interval [CI] = -0.11 to -0.04, P < .001; multivariable IVW: β = -0.06, 95% CI = -0.11 to -0.02, P = .007). Similarly, genetic predisposition to alcohol consumption was causally associated with shorter telomere length (univariable IVW: β = -0.06, 95% CI = -0.10 to -0.02, P = .006; multivariable IVW: β = -0.06, 95% CI = -0.11 to -0.01, P = .030). No pleiotropy was identified in either univariable or multivariable MR analyses. The Steiger filtering test validated the accuracy of directional causality (P < .001). Finally, leave-one-out analysis and funnel plots further confirmed the robustness and reliability of the findings. This study provides genetic evidence for the causal effects of smoking and alcohol consumption on telomere shortening. Interventions targeting tobacco smoking and alcohol consumption may slow down cellular senescence and mitigate the risk of age-related diseases.},
}

Humans
Mendelian Randomization Analysis
*Alcohol Drinking/genetics/adverse effects/epidemiology
*Smoking/genetics/adverse effects/epidemiology
*Telomere Shortening/genetics
*Telomere/genetics
Male

@article {pmid41027922,
year = {2025},
author = {Qiao, J and Wang, Q and Zhao, Y and Chang, M and Sun, S and Zhang, P and Yao, K and Chen, M and Zheng, L and Xing, X and Cai, L and Jegga, AG and Jiang, L and Pauklin, S and Zou, R and Yang, Y and Feng, Y},
title = {Contribution of leukocyte telomere length to cardiovascular disease onset from genome-wide cross-trait analysis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8677},
pmid = {41027922},
issn = {2041-1723},
support = {C59392/A25064//Cancer Research UK (CRUK)/ ; },
mesh = {Humans ; *Leukocytes/metabolism ; Genome-Wide Association Study ; *Cardiovascular Diseases/genetics ; *Telomere/genetics/metabolism ; Mendelian Randomization Analysis ; *Telomere Homeostasis/genetics ; Male ; Female ; Genetic Predisposition to Disease ; *Telomere Shortening/genetics ; Polymorphism, Single Nucleotide ; Middle Aged ; },
abstract = {Telomere shortening is a well-established marker of cellular aging and genomic instability. While the relationship between leukocyte telomere length and cardiovascular diseases has long been of interest, their genetic interplay remains incompletely understood. In this study, we observe substantial genetic overlap beyond genome-wide correlations and identify a potential causal relationship between leukocyte telomere length and coronary artery disease. Specifically, we discover 248 pleiotropic loci, 22 of which show strong evidence of colocalization. Some shared loci implicate multiple pleiotropic genes across different trait pairs, including ALDH2, ACAD10, TMEM116, SH2B3 (all at 12q24.12), TMED6 (16q22.1), SERPINF1 (17p13.3), and XPO7 (8p21.3). Functional analysis highlights key pathways involved in DNA biosynthesis and telomere maintenance. Notably, SH2B3 is validated through proteome-wide Mendelian randomization analysis, suggesting its potential as a therapeutic target. Here we report the shared genetic basis between leukocyte telomere length and cardiovascular diseases, providing valuable insights into future therapeutic developments.},
}

Humans
*Leukocytes/metabolism
Genome-Wide Association Study
*Cardiovascular Diseases/genetics
*Telomere/genetics/metabolism
Mendelian Randomization Analysis
*Telomere Homeostasis/genetics
Male
Female
Genetic Predisposition to Disease
*Telomere Shortening/genetics
Polymorphism, Single Nucleotide
Middle Aged

@article {pmid41027193,
year = {2025},
author = {Yang, L and Wang, W and Zhang, A},
title = {PARP1 promoter hypermethylation promotes arsenic-induced skin damage by driving telomere dysfunction-mediated keratinocyte senescence.},
journal = {Ecotoxicology and environmental safety},
volume = {304},
number = {},
pages = {119108},
doi = {10.1016/j.ecoenv.2025.119108},
pmid = {41027193},
issn = {1090-2414},
abstract = {Arsenic, a common environmental pollutant, causes skin damage with long-term exposure. Although its pathogenic mechanism remains unclear, skin cell senescence creates a microenvironment that promotes cancer development, with the mechanisms accelerating disease progression in arsenic-induced skin damage attracting significant attention. This study utilised previously collected skin samples to evaluate the associations between skin senescence and damage indicators. According to the presence or absence of arsenic exposure, participants were divided into a reference group and an arsenic exposure group. Additionally, the arsenic exposure group was further divided into a common pathological changes group, a hyperkeratosis group, and a skin cancer group, based on skin histopathological examination. Compared with the reference group, the arsenic exposure group exhibited increased expression of senescence-associated secretory phenotypes (IL-6 and IL-17) and shortened relative telomere length (RTL). With increasing severity of skin damage, IL-6 and IL-17 levels progressively increased, while RTL progressively decreased. Examination of representative indicators of arsenic-induced skin damage (epithelial-mesenchymal transition [EMT] indicators) revealed decreased E-cadherin expression and increased vimentin expression. With increasing severity of skin damage, E-cadherin expression progressively decreased, while vimentin expression progressively increased. Moreover, clear correlations were observed between senescence-related markers (IL-6, IL-17, and RTL) and arsenic-induced skin damage markers (E-cadherin, vimentin) in the human samples. In vitro experiments demonstrated that arsenic induced lower expression of the telomere-related gene PARP1, reducing its binding to TERF2 and weakening its recruitment of BLM, thereby causing telomere dysfunction, promoting the senescence of HaCaT cells, and resulting in EMT. Additionally, arsenic exposure induced high expression of DNMT3, which mediated PARP1 hypermethylation and low expression. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored PARP1 expression in arsenic-treated HaCaT cells, regulated telomere dysfunction, improved cellular senescence, and alleviated EMT. This study provides new insights into the mechanisms underlying arsenic-induced skin damage from an epigenetic and genetic perspective.},
}

@article {pmid41026782,
year = {2025},
author = {Sengupta, A and Vinayagamurthy, S and Soni, D and Deb, R and Mukherjee, AK and Dutta, S and Jaiswal, J and Yadav, M and Sharma, S and Bagri, S and Roy, SS and Poonia, P and Singh, A and Khanna, D and Bhatt, AKK and Sharma, A and Saurav, S and Motiani, RK and Chowdhury, S},
title = {Telomeres control human telomerase (TERT) expression through non-telomeric TRF2.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41026782},
issn = {2050-084X},
support = {IA/S/18/2/504021//Wellcome Trust/DBT India Alliance/ ; },
mesh = {Humans ; *Telomerase/genetics/metabolism/biosynthesis ; *Telomeric Repeat Binding Protein 2/metabolism ; *Telomere/metabolism ; Promoter Regions, Genetic ; Cell Line, Tumor ; },
abstract = {The function of the human telomerase reverse transcriptase (referred hereafter as TERT) in the synthesis and maintenance of chromosome ends, or telomeres, is widely understood. Whether and how telomeres, on the other hand, influence TERT regulation is relatively less studied. We found TERT was transcriptionally altered depending on telomere length (TL). This resulted from TL-dependent binding of TRF2 between telomeres and the TERT promoter. TERT promoter-bound TRF2 was non-telomeric and did not involve the looping of telomeres to the TERT promoter. Cell lines from different tissue types fibrosarcoma (HT1080), colon cancer (HCT116), and breast cancer (MDA-MB-231), engineered for either telomere elongation/shortening, gave an increase/decrease in TERT, respectively. Mechanistically, we show TERT promoter-bound non-telomeric TRF2 recruits the canonical PRC2-complex, inducing repressor histone H3K27-trimethylation in a TL-dependent fashion. This was further supported by TL-dependent promoter activity from an exogenously inserted TERT reporter. Increase in TL over days followed by a gradual decline, resulted in activation followed by repression of TERT in a concerted manner, further implicating TL as a key factor for TERT regulation. Notably, on reprogramming primary fibroblasts to induced pluripotent stem cells (iPSCs), TRF2 loss from the TERT promoter was evident along with telomere elongation and TERT upregulation. Conversely, on telomere shortening in iPSCs, TERT promoter-bound TRF2 was restored with a marked reduction in TERT, further supporting the causal role of TL in TERT transcription. Mechanisms of tight control of TERT by TL shown here are likely to have major implications in telomere-related physiologies, particularly, cancer, ageing, and pluripotency.},
}

Humans
*Telomerase/genetics/metabolism/biosynthesis
*Telomeric Repeat Binding Protein 2/metabolism
*Telomere/metabolism
Promoter Regions, Genetic
Cell Line, Tumor

@article {pmid41026280,
year = {2025},
author = {Zhao, J and Zhu, J and Zhu, K and Wang, M and Gong, W and Wang, J and Liu, S},
title = {TERT links telomere length to cancer risk by integrating genomic instability and immune modulation.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1788},
pmid = {41026280},
issn = {2730-6011},
support = {No. 82303289//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 23YF1426000//Shanghai Sailing Program/ ; },
abstract = {BACKGROUND: Telomere homeostasis serves as a key regulatory mechanism linking aging and cancer. While telomere attrition imposes a proliferative barrier by inducing cellular senescence, abnormal telomere elongation circumvents this constraint, thereby granting malignant cells unlimited replicative capacity. This study systematically explores the causal relationship between telomere length and cancer risk, with the goal of elucidating the molecular pathways involved in telomere-driven tumorigenesis.

METHOD: Mendelian randomization (MR) was employed to establish a causal link between telomere length and pan-cancer susceptibility. Multiple MR models were employed to ensure the robustness of the results. Telomere-associated genes were identified through SNPense analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Key gene regulatory networks were identified and visualized using the MCODE and cytoHubba algorithms. The expression profile of TERT across diverse cancer types was analyzed using TCGA datasets, and its diagnostic potential was evaluated via receiver operating characteristic (ROC) curve analysis. Correlations between TERT expression and immune cell infiltration were further explored.

RESULTS: Longer telomere length was significantly associated with an increased risk of 33 cancer types (IVW OR = 1.27-1.41, all P < 0.001). A total of 143 telomere-related genes were identified, with functional enrichment highlighting their involvement in genome integrity and telomere maintenance. TERT emerged as the most influential hub gene (MCC score = 169). Transcriptomic analyses from TCGA demonstrated widespread TERT overexpression in 16 cancers (e.g., CHOL, LIHC, LUAD), a finding corroborated by RT-qPCR validation. TERT exhibited high diagnostic performance (AUC > 0.85 in 16 cancers, peaking at AUC = 0.97 in LUSC). Immune infiltration analysis revealed a positive correlation with Th2 cells (r = 0.42) but negative correlations with dendritic cells (r = - 0.38) and macrophages (r = - 0.31).

CONCLUSION: This study proposes a comprehensive framework linking telomere length regulation to cancer progression through the TERT axis. Telomere dysfunction contributes to tumorigenesis via two key mechanisms: promoting genomic instability and altering the immune microenvironment. These findings offer new insights into telomere-driven oncogenesis and lay a conceptual foundation for precision diagnostics and targeted therapies in oncology.},
}

@article {pmid41024124,
year = {2025},
author = {Palomares, D and Vanparys, AAT and Jorgji, J and Paître, E and Kienlen-Campard, P and Suelves, N},
title = {Telomere-driven senescence accelerates tau pathology, neuroinflammation and neurodegeneration in a tauopathy mouse model.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {206},
pmid = {41024124},
issn = {2051-5960},
support = {40015405/40030154//FRS-FNRS (Fonds National pour la Recherche Scientifique)/ ; FNRS J.0106.22//FRS-FNRS (Fonds National pour la Recherche Scientifique)/ ; SAO-FRA 2018/0025//SAO-FRA Alzheimer Research Foundation/ ; SAO-FRA 2020/0028//SAO-FRA Alzheimer Research Foundation/ ; ARC21/26-114//UCLouvain Action de Recherche Concertée/ ; FMRE AlzHex//Queen Elisabeth Medical Foundation/ ; },
mesh = {Animals ; *Tauopathies/pathology/metabolism/genetics ; Mice ; *tau Proteins/metabolism/genetics ; Disease Models, Animal ; *Telomere/pathology/metabolism ; *Neuroinflammatory Diseases/pathology/metabolism ; *Cellular Senescence/physiology ; *Brain/pathology/metabolism ; Mice, Knockout ; Mice, Transgenic ; *Aging/pathology ; Mice, Inbred C57BL ; *Nerve Degeneration/pathology/metabolism ; Male ; },
abstract = {The connection between aging and neurodegenerative pathologies like Alzheimer's disease (AD) has long been recognized, with senescent brain cells building up in the brains of AD patients. A causal link has been established between senescence and AD-related tauopathy, but the mechanisms underlying these pathological changes remain largely unknown. To unravel the precise role of cellular senescence in tau-mediated neuropathology, we crossed the Terc knockout (Terc[-/-]) mouse model of telomere-induced senescence with the P301S tauopathy model (PS19 line). Using brain sections and protein extracts, an array of biochemical and molecular techniques was applied to investigate the expression of tau-related neuropathological features within a senescent context. Our results showed that the brains of 6- and 9-month-old Terc[-/-] mice exhibit significant telomere attrition and signs of cellular senescence. Additionally, we found evidence that the introduction of a senescent phenotype in a tauopathy mouse model results in increased tau phosphorylation at key residues, particularly in the hippocampus. Over time, this leads to enhanced tau truncation and aggregation, accompanied by exacerbated astrocyte and microglial activation, as well as selective neuronal loss in vulnerable brain regions. Overall, these findings place senescence as a key upstream regulator of tau pathology and tau-related neurodegeneration, suggesting that targeting senescent cells and their detrimental effects may offer promising therapeutic strategies for AD and other related tauopathies.},
}

Animals
*Tauopathies/pathology/metabolism/genetics
Mice
*tau Proteins/metabolism/genetics
Disease Models, Animal
*Telomere/pathology/metabolism
*Neuroinflammatory Diseases/pathology/metabolism
*Cellular Senescence/physiology
*Brain/pathology/metabolism
Mice, Knockout
Mice, Transgenic
*Aging/pathology
Mice, Inbred C57BL
*Nerve Degeneration/pathology/metabolism
Male

@article {pmid41024106,
year = {2025},
author = {Tire, B and Talibova, G and Bilmez, Y and Ozturk, S},
title = {Superovulation alters telomere length and telomerase component levels in mouse oocytes.},
journal = {Journal of ovarian research},
volume = {18},
number = {1},
pages = {210},
pmid = {41024106},
issn = {1757-2215},
mesh = {Animals ; *Telomerase/metabolism/genetics ; *Oocytes/metabolism ; *Superovulation ; Female ; Mice ; *Telomere/metabolism ; Estradiol/blood ; Progesterone/blood ; *Telomere Homeostasis ; },
abstract = {Assisted reproductive technologies (ARTs) are widely used to treat infertility and include the fundamental step, controlled ovarian stimulation (also known as superovulation). Superovulation involves the administration of gonadotropins to produce a sufficient number of oocytes, either through single or repeated applications. However, superovulation can cause certain adverse effects such as increased oxidative stress, decreased oocyte quality, and mitochondrial dysfunction. As oxidative stress and mitochondrial dysfunction are closely associated with alterations in telomere length, we investigated the effects of single and repeated superovulation on expression of the telomerase components and telomere length in mouse oocytes at germinal vesicle (GV) or metaphase II (MII) stage. Additionally, we measured serum levels of estradiol, progesterone, and oxidative markers. Our findings revealed that superovulation significantly affected telomere length, TERT protein level, telomerase RNA component (Terc), and telomerase reverse transcriptase (Tert) mRNA levels in these oocytes possibly due to altered estradiol and progesterone profiles (P < 0.05). These results suggest that altered telomerase expression and telomere length may contribute to emerging adverse effects of superovulation during oocyte maturation and early embryo development.},
}

Animals
*Telomerase/metabolism/genetics
*Oocytes/metabolism
*Superovulation
Female
Mice
*Telomere/metabolism
Estradiol/blood
Progesterone/blood
*Telomere Homeostasis

@article {pmid41022004,
year = {2025},
author = {Yang, Z and Li, J and Jin, W and Cai, D and Zhang, J and Hong, S},
title = {Kisspeptin-54 ameliorates chondrocyte senescence in osteoarthritis via SIRT3-mediated telomere protection and p53 acetylation inhibition.},
journal = {Neuropeptides},
volume = {114},
number = {},
pages = {102562},
doi = {10.1016/j.npep.2025.102562},
pmid = {41022004},
issn = {1532-2785},
abstract = {BACKGROUND: Osteoarthritis (OA), characterized by chondrocyte senescence and oxidative stress, affects over 300 million people globally. Kisspeptin-54, a neuropeptide with pleiotropic protective effects, was investigated for its role in chondrocyte senescence and its underlying mechanisms.

METHODS: Oxidative stress and senescence were induced in primary mouse chondrocytes by treating them with TBHP. Kisspeptin-54 was administered at varying concentrations (10-1000 nM) to assess cytoprotection, while SIRT3 was knocked down using adenoviral shRNA to validate mechanistic pathways. Telomere length, mTERT expression, telomerase activity, and p53 acetylation were evaluated via Southern blot, RT-PCR, and western blot techniques. Furthermore, senescence was evaluated through the application of SA-β-galactosidase staining alongside the measurement of PAI-1 expression.

RESULTS: TBHP induced dose-dependent GPR54 downregulation, oxidative stress (260 % increase in ROS), telomere attrition (41 % reduction in length), and senescence (270 % increase in SA-β-galactosidase-positive cells). Kisspeptin-54 (≤200 nM) rescued cell viability, reduced LDH release (57 % at 200 nM), and mitigated ROS and SOD activity decline. Mechanistically, Kisspeptin-54 restored SIRT3 expression, suppressed p53 acetylation (Acetyl-p53[K382] reduced by 56 % at 200 nM), and preserved telomere function (telomere length restored to 91 % of control). SIRT3 knockdown abrogated these effects, confirming its critical role.

CONCLUSION: Kisspeptin-54 alleviates chondrocyte senescence via a dual mechanism: (1) SIRT3-mediated restoration of mitochondrial antioxidant capacity and telomere homeostasis; (2) inhibition of p53 hyperacetylation and downstream senescence signaling. These findings establish Kisspeptin-54 as an innovative therapeutic candidate for OA acting through the modulation of the SIRT3/p53 axis to combat oxidative stress and telomere dysfunction.},
}

@article {pmid41016118,
year = {2025},
author = {Bountziouka, V and Nelson, CP and Codd, V and Samani, NJ},
title = {Higher dietary n - 3 PUFA and fiber intake are associated with longer leukocyte telomere length: Evidence from a substitution model analysis in the UK Biobank.},
journal = {Nutrition research (New York, N.Y.)},
volume = {142},
number = {},
pages = {63-75},
doi = {10.1016/j.nutres.2025.08.009},
pmid = {41016118},
issn = {1879-0739},
abstract = {Telomere attrition is a biomarker of cellular aging, influenced by lifestyle and dietary exposures. The specific role of macronutrient composition, particularly polyunsaturated fatty acids (PUFAs), in telomere dynamics remains insufficiently explored. We hypothesized that higher intake of specific macronutrients, particularly PUFAs, would be positively associated with leukocyte telomere length (LTL). In this cross-sectional study of 143,553 UK Biobank participants aged 40-69 years, we examined associations between macronutrient intake and standardized LTL (z-LTL), measured as the log-transformed telomere repeat to single-copy gene ratio. Dietary intake was assessed using repeated 24-hour web-based dietary recalls. Multivariable linear regression models were used to estimate associations between macronutrients (% of total energy intake) and z-LTL, adjusting for demographic, lifestyle, and clinical covariates. Effect estimates were translated into age-equivalent changes in LTL. Carbohydrate and total fat intake were positively associated with z-LTL, corresponding to age-related LTL differences of approximately 30-40 days. In energy substitution models, n - 3 PUFA intake showed a stronger positive association with z-LTL than other fats, with adherence to recommended intake associated with differences equivalent to over 2 years (P < .0001) of age-related telomere shortening, whereas no evidence of an association for MUFA was observed. Energy-adjusted fibre intake was associated with an age-related change of LTL equivalent to 1 year (P < .0001). These findings suggest that dietary composition, particularly n - 3 PUFA intake, may be linked with LTL in a manner consistent with healthier cellular aging. Further longitudinal and experimental studies are needed to confirm these associations and explore their implications for dietary guidance.},
}

@article {pmid41016064,
year = {2025},
author = {Shen, T and Ning, Y and Wang, Y and Song, Z and Xi, M and Pan, H and Xu, M},
title = {Haplotype-resolved telomere-to-telomere genome assembly of Populus lasiocarpa unveils retrotransposon-driven centromere evolution.},
journal = {The Plant journal : for cell and molecular biology},
volume = {123},
number = {6},
pages = {e70504},
doi = {10.1111/tpj.70504},
pmid = {41016064},
issn = {1365-313X},
support = {2022YFD2200301//National Key Research and Development Program of China/ ; },
mesh = {*Retroelements/genetics ; *Centromere/genetics ; *Populus/genetics ; *Telomere/genetics ; *Genome, Plant/genetics ; Evolution, Molecular ; Haplotypes/genetics ; Chromosomes, Plant/genetics ; },
abstract = {Centromeres, essential for chromosome segregation, exhibit remarkable evolutionary dynamism in sequence composition and structural organization. Here, we report the first haplotype-resolved, telomere-to-telomere genome assembly of Populus lasiocarpa (PLAS) and precisely map all 38 functional centromeres through CENH3 ChIP-Seq. Unlike classical satellite-rich centromeres in model plants, PLAS centromeres lack abundant satellite arrays but are dominated by retrotransposons, particularly RLG and RIL elements, which form intricate nested TE arrays within the functional centromeric regions, disrupting their structural integrity and driving their evolution. Comparative analysis with P. trichocarpa reveals a conserved retrotransposon-dominated architecture, despite minimal sequence conservation. We propose a cyclic model of centromere evolution in which autonomous retrotransposons destabilize functional centromeres through epigenetic erosion, triggering neocentromere formation at pericentromeric sites enriched in transposable elements (TEs) and tandem repeats (TRs). These neocentromeres either succumb to recurrent retrotransposon invasions or stabilize through KARMA-mediated TR expansion, ultimately giving rise to satellite-rich centromeres. Our work redefines centromeres as dynamic, epigenetically plastic domains shaped by retrotransposon-TR antagonism, challenging the satellite-centric paradigm and offering novel insights into plant genome evolution.},
}

*Retroelements/genetics
*Centromere/genetics
*Populus/genetics
*Telomere/genetics
*Genome, Plant/genetics
Evolution, Molecular
Haplotypes/genetics
Chromosomes, Plant/genetics

@article {pmid41015547,
year = {2025},
author = {Ginevičienė, V and Pranckevičienė, E and Urnikytė, A and Jurkūnaitė, L and Gutauskaitė, K and Dadelienė, R and Kilaitė, J and Jamontaitė, IE and Mastavičiūtė, A and Ahmetov, II and Alekna, V},
title = {A multi-omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP092853},
pmid = {41015547},
issn = {1469-445X},
support = {S-MIP-22-36//Research Council of Lithuania (LMTLT)/ ; },
abstract = {Sarcopenia and frailty are complex geriatric syndromes influenced by a combination of genetic and environmental factors. Recent studies suggest that specific genetic variants, DNA methylation patterns and shortened telomeres are associated with age-related diseases and might contribute to the development of both sarcopenia and frailty. In this study, we investigated the contribution of multi-omics data to sarcopenia, frailty, lean mass index (LMI) and handgrip strength in an elderly Lithuanian population. A total of 204 participants (age 82.2 ± 7.6 years) were included, comprising 122 individuals diagnosed with sarcopenia and/or frailty and 82 healthy, community-dwelling older adults. The results showed that LMI was associated with various health and lifestyle factors. Two genetic variants, CLIC5 rs75652203 and GHITM rs17102732, were found to be significantly associated with handgrip strength at the genome-wide level. Additionally, 12 polymorphisms previously linked to sarcopenia were replicated in relationship to LMI: BOK rs76993203, VAMP5 rs1374370, TMEM18 rs12714414, SFMBT1 rs36033494, BANK1 rs13136118, TET2 rs2647239, FOXO3 rs9384679, L3MBTL3 rs13209574, ZFAT rs13267329, CEP57 rs35793328, PCGF2 rs1985352 and MC4R rs66922415. Furthermore, several genes, many of which are involved in immune system processes, were significantly enriched with differentially methylated sites associated with LMI. Shorter telomeres were also associated with both sarcopenia and frailty. Notably, a significant relationship was observed between telomere length and methylation levels in genes related to lifestyle traits and the risk of developing these conditions. These findings provide new insights into the biological mechanisms underlying sarcopenia and frailty, underscoring the important roles of genetic and epigenetic factors in their pathogenesis among older adults.},
}

@article {pmid41014975,
year = {2025},
author = {Liu, Q and Lei, X and Fu, W and Fan, G and Fang, Q and Luo, F and Huang, X and Li, H and Guo, W and Liu, B and Yan, L and Wei, J and Wang, Y and Song, L and Hu, L},
title = {Associations of greenness and air pollution with leukocyte telomere length in Chinese children and adolescents.},
journal = {Ecotoxicology and environmental safety},
volume = {304},
number = {},
pages = {119122},
doi = {10.1016/j.ecoenv.2025.119122},
pmid = {41014975},
issn = {1090-2414},
abstract = {Evidence on the associations of greenness and air pollution with telomere length (TL) in children and adolescents remains scarce, and the potential role of air pollution in the greenness-TL association is unclear. We aimed to evaluate the relationships of greenness and air pollution with leukocyte TL (LTL) in children and adolescents and further explore further explore the interaction and mediation of air pollution on the greenness-LTL association. In this cross-sectional study, 1151 children and adolescents aged 6-18 years were recruited from Liuzhou, China. Greenness (measured by the soil-adjusted vegetation index [SAVI], normalized difference vegetation index [NDVI], and enhanced vegetation index [EVI]) and air pollution (PM2.5, PM10, NO2, SO2, and CO) were estimated based on participants' school and home addresses. Multiple linear regression models were employed to assess the associations of greenness and air pollution with LTL. An interquartile range (IQR) increment in SAVI500 m was associated 3.32 % (95 % confidence interval [CI]: 1.17 %, 5.51 %) longer LTL, while an IQR increment in PM2.5, PM10, NO2, SO2, and CO were associated with 2.26 % (95 % CI: -4.32 %, -0.16 %), 5.20 % (95 % CI: -7.48 %, -2.85 %), 9.90 % (95 % CI: -13.33 %, -6.34 %), 7.64 % (95 % CI: -11.21 %, -3.91 %), and 6.61 % (95 % CI: -9.77 %, -3.35 %) shorter LTL, respectively. Interaction and mediation were identified for PM10, SO2, NO2, and CO in the greenness-LTL association with mediation proportions from 37.90 % to 68.69 %. In conclusion, greenness exposure was positively associated with leukocyte telomere length in children and adolescents, and this association is primarily mediated by the attenuation of air pollution exposure.},
}

@article {pmid41013913,
year = {2025},
author = {Liu, Y and Zong, H and Xing, Y and Jiao, X and Liu, Z and Niu, Y and Yang, Z and Liu, S and Wang, Y and Zhao, H and Chen, X and Li, Z and Wang, X and Cai, J and Wang, W and Wang, Z},
title = {A Near Telomere-To-Telomere Genome Assembly of Coffea arabica (Mundo Novo) Provides Insights Into Its Secondary Metabolism.},
journal = {Molecular ecology resources},
volume = {},
number = {},
pages = {e70053},
doi = {10.1111/1755-0998.70053},
pmid = {41013913},
issn = {1755-0998},
support = {//The New Cornerstone Science Foundation (to WW)/ ; 32371499//National Natural Science Foundation of China/ ; },
abstract = {Arabica coffee (Coffea arabica) dominates global coffee production, accounting for over 60% of the world's coffee trade. The Mundo Novo cultivar, predominantly grown in Yunnan, China, represents a significant germplasm resource. However, the absence of a high-quality reference genome has hindered comprehensive genetic research and in-depth investigation of secondary metabolic pathways in Arabica. In this study, we present the first near telomere-to-telomere (T2T) genome assembly of Arabica, achieved through the integration of PacBio HiFi, Oxford Nanopore ultra-long, and Hi-C sequencing technologies, representing the highest-quality Arabica genome to date. Phylogenetic analysis of N-methyltransferases (NMTs), the key enzymes responsible for caffeine biosynthesis, revealed their independent evolution across caffeine-producing clades including coffee, cacao, and tea. Furthermore, GO enrichment analysis of expanded gene families at the Arabica ancestral node, combined with fruit-specific transcriptomic profiling, revealed that glycosyltransferases likely play a critical role in the secondary metabolism of Arabica. Notably, functional characterisation demonstrated that a UGT (uridine diphosphate glycosyltransferase, UGT) from the UGT29 subfamily, which exhibited increased gene copy number in the Arabica subgenome C than its ancestor, can directly convert Rebaudioside A (Reb A) into Rebaudioside M (Reb M) through a single-step enzymatic glycosylation. This direct pathway represents a crucial advancement over conventional multi-UGTs biosynthetic routes of Reb M, which is a highly desirable sweetener whereas with limited natural abundance. Taken together, this study not only provides a valuable genomic resource for studying the unique secondary metabolic processes in C. arabica but also accelerates innovative research frontiers for the synthetic biological production of the valuable sweetener Reb M.},
}

@article {pmid41010500,
year = {2025},
author = {Farhat, G and Malla, J and Hanson, L and Vadher, J and Al-Dujaili, EAS},
title = {Effects of Pomegranate Extract on IGF-1 Levels and Telomere Length in Older Adults (55-70 Years): Findings from a Randomised Double-Blinded Controlled Trial.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
pmid = {41010500},
issn = {2072-6643},
support = {Euromed Spain (No number)//Euromedik/ ; },
mesh = {Humans ; *Pomegranate/chemistry ; Middle Aged ; Double-Blind Method ; Aged ; *Insulin-Like Growth Factor I/metabolism ; Male ; Female ; *Plant Extracts/pharmacology ; *Telomere/drug effects ; Antioxidants/pharmacology ; },
abstract = {Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high antioxidant capacity, has shown promise in preventing telomere shortening and enhancing IGF-1 levels, but evidence in humans is lacking. Objective: To investigate the effects of pomegranate extract on telomere length and serum IGF-1 levels in older adults aged 55-70 years. Methods: Participants took part in a two-arm double-blind parallel trial, receiving either placebo capsules (maltodextrin) or pomegranate extract (740 mg) daily for 12 weeks. At baseline, week 6 and week 12, anthropometric measurements, blood pressure readings and blood samples were collected. Telomere length and serum IGF-1 levels were assessed. Results: A total of 72 participants completed the study. Analysis showed a significant effect of treatment and time on IGF-1 ((F2,136 = 3.43, p = 0.04), with levels significantly increasing in the pomegranate extract group at week 12. No significant effects on telomere length were noted. Weight status, physical activity, age, gender and energy intake did not impact the outcomes. Conclusions: Pomegranate extract significantly increased IGF-1 levels and could exert a positive role on vascular ageing. Further research is needed to replicate these findings and confirm its long-term benefits. Extended studies are required to elucidate its potential to counteract telomere shortening.},
}

Humans
*Pomegranate/chemistry
Middle Aged
Double-Blind Method
Aged
*Insulin-Like Growth Factor I/metabolism
Male
Female
*Plant Extracts/pharmacology
*Telomere/drug effects
Antioxidants/pharmacology

@article {pmid41010410,
year = {2025},
author = {Lin, CY and Chen, CW and Chu, PL},
title = {Examining the Relationships Between Blood Cadmium, DNA Methylation Biomarker, Telomere Length, and Their Associations with Mortality in U.S. Adults.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
pmid = {41010410},
issn = {2075-1729},
abstract = {Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = -0.043, 95% CI: -0.059 to -0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = -0.010, 95% CI: -0.014 to -0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of -0.044, a direct effect of -0.027, and an indirect effect of -0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results.},
}

@article {pmid41006252,
year = {2025},
author = {Fernandez, A and Zhou, T and Lei, Y and Liu, N and Esworthy, S and Shen, C and Liu, H and Hess, JD and Yuan, H and Shi, G and Zhou, M and Shen, L and Zhang, S and Kosiyatrakul, S and Gaur, V and Sommers, JA and Srivastava, N and Edelmann, W and Li, GM and Brosh, RM and Chai, W and Lee, MYWT and Zhang, D and Schildkraut, C and Zheng, L and Shen, B},
title = {DNA2 and MSH2 cooperatively repair stabilized G4 and allow efficient telomere replication.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8519},
pmid = {41006252},
issn = {2041-1723},
support = {R01 CA085344/CA/NCI NIH HHS/United States ; R50 CA211397/CA/NCI NIH HHS/United States ; },
mesh = {*MutS Homolog 2 Protein/metabolism/genetics ; *Telomere/metabolism/genetics ; *DNA Replication ; *G-Quadruplexes ; Humans ; *DNA Helicases/metabolism/genetics ; *DNA Repair ; Animals ; },
abstract = {G-quadruplexes (G4s) are widely existing stable DNA secondary structures in mammalian cells. A long-standing hypothesis is that timely resolution of G4s is needed for efficient and faithful DNA replication. In vitro, G4s may be unwound by helicases or alternatively resolved via DNA2 nuclease mediated G4 cleavage. However, little is known about the biological significance and regulatory mechanism of the DNA2-mediated G4 removal pathway. Here, we report that DNA2 deficiency or its chemical inhibition leads to a significant accumulation of G4s and stalled replication forks at telomeres, which is demonstrated by a high-resolution technology: Single molecular analysis of replicating DNA (SMARD). We further identify that the DNA repair complex MutSα (MSH2-MSH6) binds G4s and stimulates G4 resolution via DNA2-mediated G4 excision. MSH2 deficiency, like DNA2 deficiency or inhibition, causes G4 accumulation and defective telomere replication. Meanwhile, G4-stabilizing environmental compounds block G4 unwinding by helicases but not G4 cleavage by DNA2. Consequently, G4 stabilizers impair telomere replication and cause telomere instabilities, especially in cells deficient in DNA2 or MSH2.},
}

*MutS Homolog 2 Protein/metabolism/genetics
*Telomere/metabolism/genetics
*DNA Replication
*G-Quadruplexes
Humans
*DNA Helicases/metabolism/genetics
*DNA Repair
Animals

@article {pmid41004216,
year = {2025},
author = {Liu, X and Liu, S and Yu, Y and Song, P and Yang, L and Liu, Z and Zhou, J and Yan, X and Ma, K and Qiu, H and Wang, X and Dong, Q},
title = {Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: results from a large-scale longitudinal cohort study.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04228},
pmid = {41004216},
issn = {2047-2986},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/epidemiology ; *Leukocytes ; Longitudinal Studies ; Middle Aged ; Aged ; *Telomere/genetics ; Mendelian Randomization Analysis ; United Kingdom/epidemiology ; Prospective Studies ; Phenotype ; Risk Factors ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown inconsistent results. We aimed to clarify this association by leveraging a large-scale prospective design and Mendelian randomisation.

METHODS: We enrolled a total of 229 022 male individuals from the UK Biobank (UKB) to investigate the association between LTL and PCa risk. We employed both unadjusted and covariates-adjusted Cox proportional hazards regression models to assess this relationship. We defined the primary outcome as the diagnosis of incident PCa using in-patient data and the death registry of the UK Biobank cohort. To validate the reliability of the primary findings, we conducted secondary analyses, including Mendelian randomisation.

RESULTS: The primary analysis demonstrated that longer LTL was substantially associated with higher risk of PCa, with associations remaining robust after adjusting for potential covariates (hazard ratio (HR) = 1.444; 95% confidence interval (CI) = 1.247, 1.673, P < 0.001). We observed similar results when LTL was analysed as both a continuous and categorical variable, and the association was shown to be inversely U-shaped. We further validated the association at the genetic level using Mendelian randomisation across different PCa databases, with results consistent with our primary analysis.

CONCLUSIONS: Our findings offer evidence that leukocyte telomere length is an important risk factor for PCa. Further studies are needed to elucidate the underlying mechanisms linking leukocyte telomere length to PCa risk.},
}

Humans
Male
*Prostatic Neoplasms/genetics/epidemiology
*Leukocytes
Longitudinal Studies
Middle Aged
Aged
*Telomere/genetics
Mendelian Randomization Analysis
United Kingdom/epidemiology
Prospective Studies
Phenotype
Risk Factors
Proportional Hazards Models

@article {pmid41002620,
year = {2025},
author = {Canale, P and Andreassi, MG},
title = {Targeting Telomere Shortening in Vascular Aging and Atherosclerosis: Therapeutic Promise of Astragalus membranaceus.},
journal = {Journal of cardiovascular development and disease},
volume = {12},
number = {9},
pages = {},
pmid = {41002620},
issn = {2308-3425},
abstract = {Telomere dysfunction has emerged as a pivotal contributor to vascular senescence, a fundamental process in the pathogenesis of age-related cardiovascular diseases such as atherosclerosis. This connection underscores the therapeutic potential of targeting telomere biology to prevent or mitigate the progression of vascular aging. In this context, Astragalus membranaceus and its bioactive constituents, including astragaloside IV, cycloastragenol, and the commercial telomerase activator TA-65, demonstrate significant promise in attenuating vascular aging and atherosclerotic disease. These compounds exert a range of pleiotropic effects, including anti-inflammatory, antioxidant, endothelial-protective, and lipid-modulating actions, while also modulating telomerase activity and supporting telomere maintenance. This review provides an overview of the mechanistic basis underlying the anti-atherosclerotic effects of Astragalus-derived compounds and underscores critical key knowledge gaps. It also outlines future research directions necessary to validate their efficacy and therapeutic potential in the prevention and treatment of atherosclerosis and other age-related vascular disorders.},
}

@article {pmid41001417,
year = {2025},
author = {Wakai, TN and Anzaku, DO and Afolabi, IS},
title = {Plasmodium telomere maintenance: uncovering the Achilles' heel for novel antimalarials.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1659175},
pmid = {41001417},
issn = {2235-2988},
mesh = {*Antimalarials/pharmacology ; *Telomere/metabolism/drug effects/genetics ; Humans ; *Plasmodium/drug effects/genetics ; Telomerase/metabolism/antagonists & inhibitors ; Malaria/drug therapy/parasitology ; Animals ; G-Quadruplexes/drug effects ; *Telomere Homeostasis/drug effects ; Telomere-Binding Proteins/metabolism ; Protozoan Proteins/metabolism ; },
abstract = {This review examines the potential of disrupting telomere maintenance in Plasmodium as a novel antimalarial strategy. Telomeres are repetitive DNA-protein structures located at chromosome termini, where they preserve genome stability and protect against degradation. Telomere maintenance is crucial for rapid growth, genome integrity, and immune evasion in Plasmodium parasites. Unlike humans, Plasmodium maintains continuous telomerase activity and uses unique telomere-binding proteins across its lifecycle. These features drive parasite virulence and antigenic variation. Emerging evidence suggests that Plasmodium telomeres harbor G-quadruplex (G4) DNA structures, which help stabilize telomeres during replication and may be good targets for small molecules to disrupt their function. Additionally, the parasite depends heavily on its telomerase catalytic subunit, PfTERT, for survival. Inhibiting PfTERT has shown promising results in blocking telomere elongation and impairing replication. Targeting this parasite-specific telomere-telomerase axis may offer a strategic means to destabilize chromosomes, weaken immune evasion, and limit parasite survival, making it a promising antimalarial approach. However, researchers must consider the risks of off-target effects in future drug designs. Though current studies are limited and remain inconclusive, we suggest that future research should investigate combining telomere-directed therapies with existing antimalarials to help overcome resistance and improve treatment outcomes. Herein, we review advances in understanding Plasmodium telomere biology, highlighting its distinct structures, critical telomere-associated proteins, and roles in pathogenesis. We further explore how selective targeting could exploit an Achilles' heel in parasite survival, offering fresh possibilities for next-generation, parasite-specific malaria therapies.},
}

*Antimalarials/pharmacology
*Telomere/metabolism/drug effects/genetics
Humans
*Plasmodium/drug effects/genetics
Telomerase/metabolism/antagonists & inhibitors
Malaria/drug therapy/parasitology
Animals
G-Quadruplexes/drug effects
*Telomere Homeostasis/drug effects
Telomere-Binding Proteins/metabolism
Protozoan Proteins/metabolism

@article {pmid41000148,
year = {2025},
author = {Zhang, F and Cheng, D and Porter, KI and Wang, S and Zhu, J},
title = {Genetic Engineering of Humanized Telomere Mice.},
journal = {Bio-protocol},
volume = {15},
number = {18},
pages = {e5445},
pmid = {41000148},
issn = {2331-8325},
abstract = {Telomere shortening is a hallmark of human aging, and telomerase regulation plays a critical role in cellular proliferation and replicative senescence. In human cells, telomere length imposes a limit on proliferative potential, a phenomenon known as the Hayflick limit. However, species-specific differences in telomere dynamics and telomerase regulation between humans and mice present challenges to using mice as accurate models for human telomere-related research. To address this limitation, we engineered a humanized telomerase gene (hmTert) in mice by replacing the non-coding sequences within the mouse Tert locus (mTert) with corresponding regulatory sequences from the human TERT gene. Breeding of these genetically modified mice resulted in progressive telomere shortening over successive generations, ultimately reaching human-like lengths (below 10 kb). This protocol outlines the development of this humanized telomere mouse model, referred to as HuT mice, offering a robust platform for studying human telomere biology and aging-related diseases. Key features • This protocol describes methods to increase the success rates of knocking in large genomic fragments (~47 kb) by integrating CRISPR-Cas9 with homologous recombination. • It enables precise engineering of a humanized telomerase gene (hmTert), faithfully recapitulating human TERT regulation and telomere length dynamics in mice.},
}

@article {pmid40995488,
year = {2025},
author = {Tian, C and Wu, Q and Chen, F and Wu, Y and Wang, J and Zhang, A and Wang, W},
title = {Dynamic Telomere Length Response to Neurodevelopmental Arsenic Exposure: Insights into Transcriptional Regulation and Neuronal Morphogenesis.},
journal = {Environment & health (Washington, D.C.)},
volume = {3},
number = {9},
pages = {1031-1042},
pmid = {40995488},
issn = {2833-8278},
abstract = {Developmental exposure to arsenic (As) has been linked to irreversible adverse health outcomes in offspring. However, the underlying molecular mechanisms remain a mystery. Here, maternal mice were exposed to As via drinking water. Subsequently, the hippocampi of their offspring were collected at different developmental stages to explore the dynamic changes during hippocampal maturation and the effects of As. Time-series RNA-seq analysis revealed a significant temporal correlation between As neurodevelopmental toxicity and the mRNA expression profile of the hippocampal region during critical postnatal developmental windows. Further, downregulation of genes associated with neurogenesis and telomere maintenance was observed. Notably, dynamic changes in hippocampal telomeres were observed in response to As exposure, with critically shortened telomeres inhibiting neural stem cells (NSCs) proliferation, impairing neuroblast maturation, and reducing the number and size of neurospheres. Additionally, the populations of BrdU[+] and MAP2[+] cells were decreased while GFAP[+] cells were increased, indicating a decline in NSCs stemness. Furthermore, As exposure significantly impaired dendritic complexity in the hippocampus of mice, altered dendritic spine morphology, and disrupted synaptic ultrastructure, ultimately leading to cognitive impairment. These findings highlight the importance of analyzing telomere dynamics in environmental toxicology and offer insights into the neurotoxic mechanisms of maternal As on offspring development.},
}

@article {pmid40995413,
year = {2024},
author = {Hong, HG and Graubard, BI and Gastwirth, JL and Kim, MO},
title = {QUANTILE REGRESSION DECOMPOSITION ANALYSIS OF DISPARITY RESEARCH USING COMPLEX SURVEY DATA: APPLICATION TO DISPARITIES IN BMI AND TELOMERE LENGTH BETWEEN U.S. MINORITY AND WHITE POPULATION GROUPS.},
journal = {The annals of applied statistics},
volume = {18},
number = {3},
pages = {2012-2033},
pmid = {40995413},
issn = {1932-6157},
support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; },
abstract = {We develop a quantile regression decomposition (QRD) method for analyzing observed disparities (OD) between population groups in socioeconomic and health-related outcomes for complex survey data. The conventional decomposition approaches use the conditional mean regression to decompose the disparity into two parts, the part explained by the difference arising from the different distributions in the explanatory covariates and the remaining part, which is unexplained by the covariates. Many socioeconomic and health outcomes exhibit heteroscedastic distributions, where the magnitude of observed disparities varies across different quantiles of these outcomes. Thus, differences in the explanatory covariates may account for varying differences in the OD across the quantiles of the outcome. The QRD can identify where there are greater differences in the outcome distribution, for example, 90th quantile, and how important the covariates are in explaining those differences. Much socioeconomic and health research relies on complex surveys, such as the National Health and Nutrition Examination Survey (NHANES), that oversample individuals from disadvantaged/minority population groups in order to provide improved precision. QRD has not been extended to the complex survey setting. We improve the QRD approach proposed in Machado and Mata (2005) to yield more reliable estimates at the quantiles, where the data are sparse, and extend it to the complex survey setting. We also propose a perturbation-based variance estimation method. Simulation studies indicate that the estimates of the unexplained portions of the OD across quantiles are unbiased and the coverage of the confidence intervals are close to nominal value. This methodology is used to study disparities in body mass index (BMI) and telomere length between race/ethnic groups estimated from the NHANES data.},
}

@article {pmid40994876,
year = {2025},
author = {Farrukh, S and Baig, S and Hussain, R},
title = {Paternal contributions to telomere reprogramming in fetal development.},
journal = {International journal of biochemistry and molecular biology},
volume = {16},
number = {2},
pages = {16-23},
pmid = {40994876},
issn = {2152-4114},
abstract = {OBJECTIVES: Telomere length, the markers of biological aging, can be influenced by risk factors that may lead to health issues like chronic non-communicable diseases. This study explored the paternal telomere length influenced by diseases like diabetes and hypertension with age and its association with newborn telomere length (TL) and the telomerase gene.

METHODS: In this cross-sectional study, 204 father-newborn dyads were recruited. The qPCR was used for the quantification of TL (T/S ratio), and Sanger sequencing was done for telomerase (TERT) genotype identification. Statistical Package for Social Sciences (SPSS) and GraphPad Prism Software were used for data analysis. The Spearman correlation was used to find an association between father and newborn TL. The Kruskal-Wallis and Mann-Whitney test was used to find differences among disease groups and TL. The P<0.05 was considered statistically significant.

RESULTS: A positive correlation (r=0.39) (P<0.0001) was seen among fathers and newborn TL. The mean TL (T/S ratio) was found to be longer in healthy fathers and their newborns (1.67±1.18, 2.36±1.39), whereas significantly shorter TL (1.41±0.98, 2.02±1.58) (P=0.000) was seen in fathers suffering from diseases. The healthy fathers and their newborns TL (2.94±0.72, 3.10±0.61) were seen longer in the 15-20 (yrs) age category. Moreover, newborns of fathers (41-45 yrs) with both diabetes and hypertension had significantly longer telomere length (3.20±2.92) compared to their fathers (1.15±1.65) (P=0.006). The TERT risk genotype AC (rs2736100) was the most prevalent among the newborn girls.

CONCLUSION: A positive association with shorter TL in newborns was found in fathers having chronic diseases such as diabetes and hypertension, highlighting the contribution of fathers in reprogramming newborns' telomere biology.},
}

@article {pmid40994006,
year = {2025},
author = {Wei, Q and Wang, W and Wang, Y and Ai, J and Hu, T and Hu, H and Wang, J and Yan, Y and Pang, H and Hu, N and Bao, C},
title = {A complete telomere-to-telomere genome assembly of Solanum melongena uncovers key regulators in pan-tissue anthocyanin biosynthesis.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101533},
doi = {10.1016/j.xplc.2025.101533},
pmid = {40994006},
issn = {2590-3462},
abstract = {We present the first gap-free and integrated cytogenetic T2T genome assembly of eggplant (Smel HQ v2.0) and shed lights into the specific roles of the SmeMYBs in anthocyanin biosynthesis across various tissues. The complete T2T eggplant genome could substantially facilitate in-depth and refined genetic and genomic studies in eggplants.},
}

@article {pmid40988089,
year = {2025},
author = {DeCleene, NF and Nguyen, DT and Kirk, SE and Helber, HL and Sasa, GS and Bertuch, AA},
title = {The diagnostic performance of the basic versus the detailed telomere Flow FISH test in young patients with aplastic anaemia.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70155},
pmid = {40988089},
issn = {1365-2141},
support = {GM136554/GM/NIGMS NIH HHS/United States ; },
abstract = {Identifying telomere biology disorders (TBDs) in patients with aplastic anaemia (AA) is essential for guiding appropriate care. Telomere length (TL) measurement by flow cytometry with fluorescence in situ hybridization supports diagnosis, but the real-world performance of the basic test (lymphocytes and granulocytes) versus the detailed test (which includes four lymphocyte subsets) remains unclear. We retrospectively reviewed 439 patients who underwent detailed TL testing at our institution from 2008 to 2022. Haematological disease was present in 87%, with AA comprising 56%. We classified 23 subjects with TBD independently of TL, only one of whom had severe AA (SAA) at initial presentation. Granulocyte numbers were insufficient for TL analysis in 28% of subjects, precluding a rigorous assessment of the impact of granulocyte TL on identification of TBD. Very low TL in lymphocytes or ≥3 lymphocyte subsets identified all TBD cases across AA severity. However, positive predictive value (PPV) was low, particularly in SAA. The detailed test had greater specificity and PPV, particularly in mild AA, which had the greatest proportion of TBD cases among those with AA, supporting its use. However, additional diagnostics, such as genetic testing, remain necessary in many cases to confirm TBD and avoid misclassification.},
}

@article {pmid40987793,
year = {2025},
author = {Raza, W and Pudas, S and Kanninen, KM and Flanagan, E and Degerman, S and Adolfsson, R and Giugno, R and Topinka, J and Zeng, XW and Oudin, A},
title = {Associations between air pollution and relative leukocyte telomere length among northern Swedish adults based on findings from the Betula study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {32660},
pmid = {40987793},
issn = {2045-2322},
mesh = {Humans ; Sweden/epidemiology ; Male ; Female ; *Air Pollution/adverse effects ; *Leukocytes/metabolism ; Aged ; Middle Aged ; *Environmental Exposure/adverse effects ; *Telomere ; *Dementia/epidemiology/etiology/genetics ; *Telomere Homeostasis ; Adult ; Particulate Matter/adverse effects ; Air Pollutants/adverse effects ; Risk Factors ; },
abstract = {Air pollution is increasingly discussed as a risk factor for dementia, but the biological mechanisms are not yet fully understood. Biological markers like telomere length are relevant to study with air pollution, as they are associated with aging and dementia. The study aimed to investigate the relationship between source-specific air pollution exposure and telomere length in a low-level air pollution area, and whether this potential relationship depended on future dementia status. The data originated from the Betula study in Northern Sweden, where 509 participants recruited between 1988 and 1995 were included to investigate the association between annual mean air pollution concentrations at the participants' residences and relative leukocyte telomere length using a linear regression model. No association was observed between air pollution and telomere length, with regression slope estimates close to zero and p-values > 0.10 (e.g. PM2.5_total: β = 0.01 (-0.011, 0.025) and BC_total: β = 0.03 (95% CI: -0.046, 0.114). There were indications of a positive association between longer telomere length and higher exposure to air pollution among individuals later diagnosed with dementia (N = 74), but these findings were not conclusive (p-values > 0.10) (PM2.5_total: β = 0.03, p-value = 0.12; BC_total: β = 0.11, p-value = 0.17). Although not statistically significant, our findings contribute to the evidence from low-exposure settings, and it is important to report these types of findings for a balanced understanding of potential health effects.},
}

Humans
Sweden/epidemiology
Male
Female
*Air Pollution/adverse effects
*Leukocytes/metabolism
Aged
Middle Aged
*Environmental Exposure/adverse effects
*Telomere
*Dementia/epidemiology/etiology/genetics
*Telomere Homeostasis
Adult
Particulate Matter/adverse effects
Air Pollutants/adverse effects
Risk Factors

@article {pmid40987381,
year = {2025},
author = {Davis, RL and Mason, SD and Wake, C and Fabozzi, G and Catalano, WL and Schramm, CA and Henry, AR and Parker, CL and Laboune, F and McLaughlin, CL and Kittilson, JD and Swaddle, JP and Cristol, DA and Heidinger, BJ and Douek, DC},
title = {Chronic Sublethal Exposure to Methylmercury Lengthens Telomeres in Developing Zebra Finches.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127148},
doi = {10.1016/j.envpol.2025.127148},
pmid = {40987381},
issn = {1873-6424},
abstract = {Methylmercury (MeHg) is a widespread environmental pollutant known to cause DNA and chromosomal damage, in part through reactive oxygen species (ROS). Telomeres, essential for chromosomal protection, are highly sensitive to oxidative damage and consequent shortening. While ROS-dependent oxidative stress accelerates telomere attrition in vitro, the mechanisms by which chronic exposure to ROS-inducing exogenous agents affects telomere length in vivo remain unclear. We studied effects of sublethal, multi-generational MeHg exposure on telomere dynamics during early life in zebra finches (Taeniopygia guttata). Continuous exposure to an environmentally relevant concentration of dietary MeHg (1.2 mg/kg) resulted in longer relative telomeres in red blood cells, brain, liver, kidney and lung by sexual maturity. No evidence of selection for longer telomeres across generations of MeHg exposure was observed. Lung protein expression of proliferating cell nuclear antigen (PCNA), a DNA synthesis marker, remained unchanged, suggesting telomere maintenance or elongation occurs independently of proliferation. However, β-Catenin expression, a key transcription factor in Wnt signaling, increased in young MeHg-exposed birds. Transcriptomic analysis of bone marrow revealed up-regulation of oncogenic and pro-inflammatory signaling pathways and down-regulation of mitotic cell cycle pathways. Combined, our data reveal cellular processes reminiscent of tumorigenesis and suggestive of replicative immortality of telomeres under chronic stress.},
}

@article {pmid40986533,
year = {2025},
author = {Tunnicliffe, L and Muzambi, R and Bartlett, JW and Howe, LD and Basit, KA and Asare, K and Gore-Langton, G and Mansfield, KE and Codd, V and Warren-Gash, C},
title = {Infection and telomere length: A systematic review.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0333107},
pmid = {40986533},
issn = {1932-6203},
mesh = {Humans ; *Telomere/genetics ; *Telomere Homeostasis ; HIV Infections/genetics ; *Telomere Shortening ; *Infections/genetics ; Aging/genetics ; },
abstract = {BACKGROUND: Infections may increase the risk of age-related diseases such as dementia. Accelerated immunological ageing, measurable by telomere length (TL), may be a potential mechanism. However, the relationship between different infections and TL or telomere attrition remains unclear. This systematic review synthesises existing evidence on whether infections contribute to TL or telomere attrition and highlights research gaps to inform future studies.

OBJECTIVE: To summarise the literature on associations between infections and telomere length or attrition.

METHODS: We conducted comprehensive searches across six databases (MEDLINE, EMBASE, Web of Science, Scopus, Global Health, Cochrane Library) from inception to 22 May 2025, using concepts of infections, TL, and study type. Two researchers independently screened studies, extracted data, and assessed risk of bias (ROB) using the ROBINS-E tool. Meta-analysis was unfeasible due to heterogeneity, so a narrative synthesis was conducted. Studies were grouped by infection type, telomere measurement assay, cell type, and statistical approach. A GRADE assessment was performed to evaluate evidence quality.

RESULTS: Our searches identified 10,349 studies, of which 73 met eligibility criteria. Most (59) were cross-sectional and most were published after 2000, with the earliest from 1996. Most studies were from the USA (17). HIV was the most frequently studied infection (35 studies), with 79% (excluding overlapping samples) reporting an association between HIV and reduced TL or increased telomere attrition. Findings for other infections, including herpesviruses and Human Papillomavirus were more variable. Variation in infection type, measurement assay, cell type, and statistical approach made cross-study comparisons challenging. Most studies had a high ROB, mainly due to unmeasured confounding. The GRADE assessment rated evidence quality as very low.

CONCLUSIONS: Our review highlights a potential link between HIV and TL and telomere attrition. More robust longitudinal studies with standardised measurements and better confounder control are needed, particularly for non-HIV infections. PROSPERO (ID:CRD42023444854).},
}

Humans
*Telomere/genetics
*Telomere Homeostasis
HIV Infections/genetics
*Telomere Shortening
*Infections/genetics
Aging/genetics

@article {pmid40983946,
year = {2025},
author = {Nguyen, L and Choi, JY},
title = {Topsicle: a method for estimating telomere length from whole genome long-read sequencing data.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {295},
pmid = {40983946},
issn = {1474-760X},
support = {R35 GM154595/GM/NIGMS NIH HHS/United States ; R35GM154595/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Telomere/genetics ; *Whole Genome Sequencing/methods ; *Telomere Homeostasis ; *Software ; },
abstract = {Telomeres protect chromosome ends and their length varies significantly between organisms. Because telomere length variation is associated with various biomedical and eco-evolutionary phenotypes, many biological fields are interested in understanding its biological significance. Here, we introduce Topsicle, a computational method that estimates telomere length from whole genome long-read sequencing data using k-mer and change-point detection analysis. Simulations show Topsicle is robust to sequencing errors and coverage. Application of Topsicle to plant and human cancer cells shows high accuracy and comparable results to direct telomere length measurements. We predict Topsicle will be a useful tool for studying telomere biology.},
}

Humans
*Telomere/genetics
*Whole Genome Sequencing/methods
*Telomere Homeostasis
*Software

@article {pmid40983034,
year = {2025},
author = {Guarnera, L and Wahida, A and Gurnari, C and Hutter, S and Stainczyk, SA and Williams, N and Durmaz, A and Kubota, Y and Bravo-Perez, C and Kawashima, N and Orland, MD and Pagliuca, S and Huang, Y and LaFramboise, T and Visconte, V and Walter, W and Meggendorfer, M and Kern, W and Westermann, F and Feuerbach, L and Haferlach, T and Maciejewski, JP},
title = {Determining telomere content and genomics of myeloid neoplasia by whole-genome sequencing.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025028644},
pmid = {40983034},
issn = {1528-0020},
abstract = {Telomere length shortening has been associated with genomic instability and acquisition of molecular lesions, but these processes have not been systematically studied across large cohorts of myeloid neoplasia (MN). As proof of concept for a novel, cross-validated WGS-based method of telomere content (TC) determination combined with mutations, transcriptomics, and functional assays, we studied TC in correlation with specific molecular features of a large cohort (n=1804) of MN patients including acute myeloid leukemia (AML) and myelodysplastic syndrome. When compared to healthy subjects and patients with non-clonal diseases such as persistent polyclonal B cell lymphocytosis, both MN and non-malignant controls with clonal disease, such as paroxysmal nocturnal hemoglobinuria and aplastic anemia, exhibited decreased TC. Furthermore, we show that TC is lowered in adult MN abrogating correlation with age with considerable TC diversification among certain morphologic and molecular subtypes. For instance, AML harbored the lowest TC. Furthermore, MN originating from a more mature cell of origin (e.g., APL), and those characterized by hyperproliferative driver mutations (e.g., RAS pathway genes) had lower TC, possibly indicating a loss of telomere maintenance capacity. In contrast, MN subtypes arising in a context of profound genetic alterations, such as TP53 mutations and complex karyotype, exhibited a relatively higher/preserved TC compared to other mutations. This phenomenon did not involve alternative lengthening processes but was rather consistent with an increased TC due to preserved activity of the telomerase complex. Our results describe a common and genotype-specific telomeric make-up of a large cohort of patients with MN providing a molecular benchmark for future therapeutic targeting of the telomere machinery.},
}

@article {pmid40982395,
year = {2025},
author = {Clatterbuck Soper, SF and Meltzer, PS},
title = {A Flexible Procedure for Performing Telomere FISH and Immunofluorescence in Cells Expressing Fluorescent Proteins.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {223},
pages = {},
doi = {10.3791/68977},
pmid = {40982395},
issn = {1940-087X},
mesh = {*In Situ Hybridization, Fluorescence/methods ; *Telomere/genetics/chemistry/metabolism ; Humans ; *Luminescent Proteins/genetics/biosynthesis/analysis/chemistry ; *Fluorescent Antibody Technique/methods ; },
abstract = {Visualizing telomeres using fluorescence in situ hybridization (TelFISH) has long been an essential tool in telomere biology experiments. Combining TelFISH with immunofluorescence (IF) is also a well-established method (IF-TelFISH), for example, in identifying telomere dysfunction-induced foci, where telomeres co-localize with 53BP1. More recently, native telomere FISH (nTelFISH) has become an important tool for assaying Alternative Lengthening of Telomeres, a telomere maintenance mechanism used in some tumor cells. Expressing fluorescent proteins is also an essential tool in cell biology, allowing visualization of proteins and structures that may remain undetectable by other methods. Because FISH buffers denature proteins, performing the assay in cells with an expressed fluorescent protein (FP) results in loss of FP signal. A method for integrating IF and telomere FISH in cells with an expressed fluorescent protein that preserves the FP signal even after FISH is described here. Alternatives are provided for denaturing and native telomere FISH in combination with several IF and FP scenarios. Taken together, this protocol offers a flexible framework for exploring telomere biology in both normal and tumor cells.},
}

*In Situ Hybridization, Fluorescence/methods
*Telomere/genetics/chemistry/metabolism
Humans
*Luminescent Proteins/genetics/biosynthesis/analysis/chemistry
*Fluorescent Antibody Technique/methods

@article {pmid40982211,
year = {2025},
author = {Ruano, JL and Bejarano, L and Serrano, R and Diaz, RA and Flores, JM and López, AC and Blasco, MA},
title = {Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206320},
pmid = {40982211},
issn = {1945-4589},
abstract = {TRF1, a component of the telomere shelterin complex, plays crucial roles in telomere protection, telomere length regulation, and stemness. Here, we describe a previously unknown connection between TRF1 and metabolism. Telomere attrition has been linked to obesity. Our study reveals that Trf1-deficient mice exhibit a leaner phenotype, reduced adiposity, and improved glucose tolerance, even when subjected to a high-fat diet, independently of telomere shortening. These findings uncover a previously unknown role of TRF1 in regulating metabolism.},
}

@article {pmid40981352,
year = {2025},
author = {Ruiz-Arias, MA and Bernal-Hernández, YY and Medina-Díaz, IM and Herrera-Moreno, JF and Barrón-Vivanco, BS and Verdín-Betancourt, FA and González-Arias, CA and Flores-Alfaro, E and Ramos, KS and Ostrosky-Wegman, P and Rojas-García, AE},
title = {Comprehensive Biomarker Assessment of Pesticide Exposure and Telomere Attrition in Mexican Children from Agricultural Communities.},
journal = {Journal of xenobiotics},
volume = {15},
number = {5},
pages = {},
pmid = {40981352},
issn = {2039-4713},
support = {This work was partially supported by CONAHCyT (Grant #314829).//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; },
abstract = {Children are more vulnerable to the adverse effects of pesticides due to physiological factors and behavioral habits. This study aimed to evaluate the impact of pesticide exposure on telomere length (TL) and the enzymatic activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and β-glucuronidase (β-Glu) in children ages 6 to 12 from an agricultural area in Mexico. A cross-sectional, descriptive, and analytical study was conducted involving 471 children. Blood samples were collected to assess TL through qPCR and enzymatic activity using established protocols. A pesticide exposure index (PEI) was developed incorporating biomarker levels, urinary dialkylphosphates (DAP), and proximity to farmland. No significant differences were observed in AChE activity across communities; however, BuChE activity was significantly higher in agricultural communities, while β-Glu activity varied among communities. Notably, children aged 6 in agricultural areas showed TL values similar to 12-year-old children in the reference community. Adjusted regression models revealed significantly shorter TL in children from agricultural communities and in children with moderate to high PEI. The findings indicate that chronic pesticide exposure was associated with telomere shortening in children, suggesting accelerated biological aging and potential genomic instability during critical developmental periods.},
}

@article {pmid40979377,
year = {2025},
author = {Ershova, ES and Umriukhin, PE and Zinchenko, RA and Vasilieva, TP and Kostyuk, SE and Shabalin, NY and Salimova, TA and Malinovskaya, EM and Veiko, NN and Kostyuk, SV},
title = {Variation in the Content of Three Tandem Repeats of the Human Genome (Ribosomal, Satellite III, and Telomere) in Peripheral Blood Leukocyte DNA of People of Different Ages (5-101 Years).},
journal = {Journal of aging research},
volume = {2025},
number = {},
pages = {8847073},
pmid = {40979377},
issn = {2090-2204},
abstract = {The variation of ribosomal (parameter R), satellite III (1q12) (parameter S), and telomere (parameter T) tandem repeats content of the human genome was studied in DNA samples isolated from blood leukocytes of 535 people whose age varied from 5 to 101 years. For analysis we used the method of nonradioactive quantitative hybridization. The group of centenarians (90-101 years old, N = 106) differs from other age groups by a significantly narrower distribution of the ribosomal repeat content in DNA, a much higher content of satellite III, and a lower content of telomere repeat. A negative correlation was found between the S and T parameters (p < 10[-4]). The findings of this study suggest that the calculated parameters S/T and S/(R∗T) exhibit a marked increase with age, culminating in maximal values within the cohort of centenarians. These results imply that the parameters R, S/T, and S/(R∗T) may hold the potential to serve as reliable predictors of life expectancy for individuals in advanced age.},
}

@article {pmid40975488,
year = {2025},
author = {Xu, S and Liu, Q and Yang, T and Han, Z},
title = {A telomere-to-telomere genome assembly of the large yellow croaker provides insights into evolution of golden-yellow coloration.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2025.09.006},
pmid = {40975488},
issn = {1673-8527},
abstract = {The large yellow croaker (Larimichthys crocea) is a flagship marine fish in China given its extreme commercial value and golden-yellow coloration. However, the genetic mechanisms underlying golden-yellow coloration remain unclear. Here, we construct a telomere-to-telomere gap-free genome assembly (T2T-Larcro_1.0) spanning 716.87 Mb, with a contig N50 of 31.75 Mb. Compared to the current reference genome (L_crocea_2.0), T2T-Larcro_1.0 incorporates 112.70 Mb of previously unassembled regions and 2368 newly anchored genes. This assembly facilitates comparative genomics analyses in sciaenids by identifying several candidate genes (e.g., OPNVA, nNOS, RDH13) potentially involved in evolution of golden-yellow coloration. Transcriptomic analyses further confirm expression of OPNVA-encoded vertebrate ancient opsin (VA opsin) in skin tissues of the large yellow croaker, suggesting its role as an extraretinal photoreceptor regulating localized golden-yellow coloration. Integrating genomics and transcriptomics results, our results uncover the triggering effect of VA opsin linking skin and neural photoreception to physiological regulation of body color change (golden-yellow to silvery-white) in L. crocea. Collectively, our findings provide molecular evidence that elucidate the underlying evolutionary mechanism of golden-yellow coloration in L. crocea. This high-quality genome assembly also serves as an improved resource for biological evolution, genetic improvement, and selective breeding of L. crocea.},
}

@article {pmid40975053,
year = {2025},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance.},
journal = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2025.08.052},
pmid = {40975053},
issn = {1879-0445},
abstract = {Telomeres are composed of specialized DNA, RNA, and proteins that interact to preserve the integrity of chromosome termini.[1][,][2] Despite this vital function, telomere length varies dramatically within and between species. Genome-wide association studies have identified multiple genes that explain a portion of this variation,[3] suggesting that telomere length is inherited as a classic quantitative trait. However, telomere length is also directly inherited as a DNA sequence. Here, we show that neither the polygenic nor the direct inheritance paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict observed differences in adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the alternative lengthening of telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.},
}

@article {pmid40973456,
year = {2025},
author = {Červenák, F and Virágová, S and Sopkovičová, M and Kodada, D and Galla, E and Sepšiová, R and Procházková, K and Tomáška, Ľ},
title = {Runaway evolution of telomeres in ascomycetous yeasts was accompanied by the replacement of ancestral telomeric proteins.},
journal = {Nucleic acids research},
volume = {53},
number = {17},
pages = {},
pmid = {40973456},
issn = {1362-4962},
support = {APVV-19-0068//Slovak Research and Development Agency/ ; APVV-23-0056//Slovak Research and Development Agency/ ; 1/0031/24//Ministry of Education, Science, Research and Sport of the Slovak republic/ ; 1R01ES031635-05/NH/NIH HHS/United States ; //European Regional Development Fund/ ; APVV-23-0056//Slovak Research and Development Agency/ ; },
mesh = {*Telomere-Binding Proteins/metabolism/genetics/chemistry ; *Telomere/metabolism/genetics/chemistry ; *Evolution, Molecular ; Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry ; Schizosaccharomyces/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry ; Saccharomyces cerevisiae/genetics/metabolism ; Yarrowia/genetics ; Phylogeny ; Shelterin Complex ; *Fungal Proteins/metabolism/genetics/chemistry ; Protein Binding ; },
abstract = {Telomeres are crucial parts of eukaryotic chromosomes, contributing to DNA replication, chromosome segregation, and genome stability. While in most phylogenetic lineages, telomere-maintenance systems are conserved, ascomycetous yeasts exhibit a high degree of variability in telomeric repeats and the associated proteins. The determinants that enabled this divergent evolutionary process, however, have been unclear. Here, we show that DNA-binding properties of yeast telomere-binding proteins (TBPs) support the scenario where the gradual divergence of telomeric repeats led to their replacement. We analyzed the DNA-protein interactions between Tay1p from Yarrowia lipolytica, Rap1p from Saccharomyces cerevisiae, and Taz1p from Schizosaccharomyces pombe and a set of telomeric repeats from several yeast species and delineated how the ancestral (Tay1p-like) TBPs were replaced by Rap1p (in budding yeasts) or Taz1p (in fission yeasts). We also postulate two different driving forces for these replacements: (i) Tay1p-to-Rap1p transition appears to be driven by differences in sequence preferences of Tay1p and Rap1p, while (ii) Taz1p became the principal TBP in fission yeast presumably due to its DNA-binding flexibility. Together, our results suggest that in telomeric DNA-protein complexes, the replacement of protein component triggered by the initial variation in DNA sequence space opens the door to further divergence in a runaway-style evolution.},
}

*Telomere-Binding Proteins/metabolism/genetics/chemistry
*Telomere/metabolism/genetics/chemistry
*Evolution, Molecular
Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry
Schizosaccharomyces/genetics/metabolism
Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry
Saccharomyces cerevisiae/genetics/metabolism
Yarrowia/genetics
Phylogeny
Shelterin Complex
*Fungal Proteins/metabolism/genetics/chemistry
Protein Binding

@article {pmid40969732,
year = {2025},
author = {Bragina, A and Tarzimanova, A and Druzhinina, N and Vasileva, L and Novikov, K and Loriya, I and Avdeenko, O and Samohlib, Y and Vlasova, N and Savina, E and Makarenko, P and Podzolkov, V},
title = {Telomere Length in Young Patients: Relationship With Metabolic Syndrome and Its Components.},
journal = {Journal of clinical medicine research},
volume = {17},
number = {8},
pages = {460-467},
pmid = {40969732},
issn = {1918-3003},
abstract = {BACKGROUND: Previous studies have reported inconsistent findings on the relationship between telomere length and metabolic syndrome (MS). The aim of the work was to study leukocyte telomere length in young patients without cardiovascular diseases and its relationship with MS and its components.

METHODS: This study included 450 Caucasian patients with a median age of 30 (21 - 42) years. Glycemic parameters and lipid profile components were determined using the CardioChek PA (USA, 2017). Integral metabolic indices were calculated in all patients. To investigate leukocyte telomere length, 45 were randomly selected from the total cohort of 450 participants.

RESULTS: The selected patients were divided into two groups according to the presence of MS. The median telomere length in MS patients (7.36 (6.96 - 8.67) pn) was significantly lower than in the comparison group (8.72 (8.37 - 8.96) pn) (P = 0.016). Correlation analysis was performed to assess the relationship between telomere length and various traditional cardiovascular risk factors (sex, age, smoking, and blood pressure levels), MS components, and integral metabolic indices. Several linear regression analysis models were constructed to assess the independent associations between various factors and telomere length. Age, smoking, neck circumference, triglycerides, high-density lipoprotein levels, LAP index, and the presence of dyslipidemia were significantly associated with telomere length.

CONCLUSION: Our results are consistent with the notion of shorter leukocyte telomere length in individuals with MS and support an association with dyslipidemia in premature shortening of telomere length. The causal relationship between these changes requires further study.},
}

@article {pmid40967766,
year = {2025},
author = {El Husseini, K and Lee, JS and Juge, PA and Ebstein, E and Ottaviani, S and Borie, R and Bancal, C and Debray, MP and Kannengiesser, C and Ba, I and Marchand-Adam, S and Richez, C and Nunes, H and Avouac, J and Flipo, RM and Wemeau, L and Boissier, MC and Schaeverbeke, T and Kermanac'h, NS and Kawano-Dourado, L and Cottin, V and Wolters, PJ and Granger, B and Dieudé, P and Crestani, B},
title = {Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.00587-2025},
pmid = {40967766},
issn = {1399-3003},
abstract = {BACKGROUND: Shorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD.

METHODS: Patients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL<10th percentile. Lung disease progression was defined as death, lung transplant or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5%predicted, transfer capacity (TLCO) ≥10%predicted).

RESULTS: Among 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82% versus 93%predicted) and TLCO (49% versus 63%predicted) at enrolment, and greater 12-months decline in FVC and DLCO in mixed effects models (-7.7%pred. 95%CI[-11.6,-3.8] p<0.001, -4.5%pred. [-7.2, -1.8] p=0.001, respectively), although transplant-free survival was similar over a median follow-up of 3.6 years (IQR[1.8,7.0]). Lung disease progression was observed within 12 months of enrolment in 33 patients (33%), more frequently in patients with short LTL (47% versus 22%, p univariate=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 95%CI[0.94,1.00] p=0.031 and 2.80 [0.99,8.29] p=0.056, respectively).

CONCLUSIONS: Short LTL is associated with baseline severity and 12-month progression in RA-ILD.},
}

@article {pmid40964771,
year = {2025},
author = {Yang, MM and Liu, S and Wax, M and Lee, S and French, S and Wolters, PJ and Boin, F},
title = {Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43400},
pmid = {40964771},
issn = {2326-5205},
abstract = {OBJECTIVE: Peripheral blood leukocyte telomere length (PBL-TL) shortening is associated with systemic sclerosis related interstitial lung disease (SSc-ILD). However, its association with other organ involvement, disease severity, and survival remains unclear. This study aimed to define the relationship of TL with SSc-specific disease manifestations and outcomes.

METHOD: PBL-TL was measured by quantitative PCR in 244 patients with SSc and 314 healthy controls. Multivariate modeling was utilized to assess the association of PBL-TL with disease severity and event-free survival. Longitudinal changes in PBL-TL were measured in a subset of patients. Telomere length was quantified in SSc skin and lung tissues by telomere fluorescence in situ hybridization.

RESULTS: PBL-TL was significantly shorter in patients with SSc than healthy controls. Shortened PBL-TL was associated with presence and severity of ILD and pulmonary hypertension (PH) with the shortest PBL-TL found in subjects with concurrent ILD and PH (p=0.04). PBL-TL was not associated with skin disease or peripheral vascular disease. Shorter PBL-TL was associated with hospitalizations (p<0.01) and worse event-free survival (p=0.03). Patients with early SSc had a faster rate of PBL-TL shortening compared to patients with longer disease duration (p = 0.04). TL was shorter in SSc-ILD lung epithelial cells (p=0.01) while no difference was found in epithelial cells of SSc skin (p=0.82).

CONCLUSION: Short PBL-TL is associated with pulmonary disease severity and predicts worse SSc clinical outcomes. This study provides rationale to further investigate the role of telomere dysfunction in SSc pathogenesis and validate TL as a prognostic biomarker in SSc.},
}

@article {pmid40958330,
year = {2025},
author = {Liu, Q and Gu, Y and Huang, H and Ren, J and Liu, Y and Wang, D},
title = {Platelet-to-lymphocyte ratio and telomere length in older adults: An inverted U-shaped nonlinear relationship: A nationwide cohort study.},
journal = {Medicine},
volume = {104},
number = {37},
pages = {e44188},
pmid = {40958330},
issn = {1536-5964},
support = {2024ZZ2072//Shanghai Municipal Health Commission Medical New Technology Research and Transformation Seed Project/ ; 2024MZYS09//Training Program for High-Level Specialist Physicians under the Collaborative Health Service System of Education, Research, and Clinical Practice in Minhang District, Shanghai City(2024-2027)/ ; 2023MHZ046//The Natural Science Research Project in Minhang District, Shanghai City/ ; },
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Blood Platelets ; *Lymphocytes ; *Telomere ; Cohort Studies ; Platelet Count ; Nutrition Surveys ; Nonlinear Dynamics ; *Telomere Homeostasis ; Aged, 80 and over ; },
abstract = {This study aimed to investigate the association between the platelet-to-lymphocyte ratio (PLR) Log and telomere length in older adults, focusing on the potential nonlinear relationship within a nationwide cohort. Data were obtained from the National Health and Nutrition Examination Survey 1999 to 2000 and 2001 to 2002 cycles, including 2660 participants aged 60 years and older. PLR Log was calculated as the log-transformed value of PLR, which was further analyzed as both a continuous variable and in quartiles. Mean telomere length (TeloMean) was measured using quantitative PCR. Linear regression, trend tests, smooth curve fitting, and segmented regression were employed to evaluate the relationship between PLR Log and TeloMean, adjusting for potential confounders. Subgroup analyses were conducted to assess variations in associations across age, sex, and other variables. An inverted U-shaped nonlinear relationship was identified between PLR Log and TeloMean. Trend analysis demonstrated a significant trend across quartiles of PLR Log in both the minimally adjusted (P for trend = .021) and fully adjusted models (P for trend = .048). Threshold effect analysis identified a breakpoint at PLR Log = 5.564, where TeloMean significantly increased with PLR Log when below this threshold (β1 = 0.034, 95% CI: 0.012-0.057, P = .003), but decreased when PLR Log exceeded this threshold (β2 = -0.115, 95% CI: -0.221 to -0.009, P = .033). This association was more pronounced in participants aged 66 to 74 years (P for interaction = .005). This study provides new insights into the relationship between systemic inflammation and telomere dynamics in older adults. The observed inverted U-shaped relationship suggests that moderate levels of inflammation may help maintain telomere integrity, possibly through improved immune regulation, while excessive inflammation may accelerate telomere attrition due to increased oxidative stress and impaired DNA repair mechanisms. These findings highlight PLR Log as a potential inflammatory biomarker for aging-related telomere dynamics and emphasize the need for further longitudinal studies to validate these associations.},
}

Humans
Male
Female
Aged
Middle Aged
*Blood Platelets
*Lymphocytes
*Telomere
Cohort Studies
Platelet Count
Nutrition Surveys
Nonlinear Dynamics
*Telomere Homeostasis
Aged, 80 and over

@article {pmid40954016,
year = {2025},
author = {Sánchez-Vázquez, R and Burgaz García-Oteyza, S and Serrano, R and Flores, JM and Martínez, P and Blasco, MA},
title = {Mice carrying the homologous human shelterin POT1-L259S mutation linked to pulmonary fibrosis show a telomerase deficiency-like phenotype with telomere shortening with increasing mouse generations.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352855.125},
pmid = {40954016},
issn = {1549-5477},
abstract = {Pulmonary fibrosis is a lethal disease associated with damaging insults to the lung and with organismal aging. The presence of short and dysfunctional telomeres has been placed at the origin of this disease in a percentage of both familial and sporadic cases. Recently, a mutation in the telomere-binding protein protection of telomeres 1 in humans (hPOT1), the hPOT1 L259S mutation, was found in families with idiopathic pulmonary fibrosis. Here, we generated a Pot1a [L261S] knock-in mouse harboring the murine homologous hPOT1 L259S mutation. We found that the homozygous Pot1a [L261S] mice show shorter telomeres and degenerative pathologies in the intestine, testes, and lungs at old ages, a phenotype that is aggravated with increasing mouse generations, in striking analogy to the telomerase-deficient mouse models. Furthermore, we found that the POT1a-L261S mutant protein binds more strongly to TPP1 and to telomerase and impedes telomerase-dependent telomere lengthening in vivo. We show that telomerase activity at telomeres is reduced in the presence of POT1a-L261S, which behaves as a dominant negative mutant, thus providing a potential mechanism by which Pot1a [L261S] knock-in mice phenocopy the short telomere phenotype of the telomerase knockout model.},
}

@article {pmid40953361,
year = {2025},
author = {Le, AD},
title = {Tracing Toxic Stress Through Telomeres: A Future Physician-Scientist's Path.},
journal = {Academic medicine : journal of the Association of American Medical Colleges},
volume = {},
number = {},
pages = {},
doi = {10.1097/ACM.0000000000006283},
pmid = {40953361},
issn = {1040-2446},
}

@article {pmid40950970,
year = {2025},
author = {Matviichuk, A and Krasnienkov, D and Yerokhovych, V and Ilkiv, Y and Korcheva, V and Gurbych, O and Shcherbakova, A and Botsun, P and Falalyeyeva, T and Sulaieva, O and Kobyliak, N},
title = {Association of leukocyte telomere length and HbA1c with post-COVID-19 syndrome in type 2 diabetes: a cross-sectional pilot study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1628156},
pmid = {40950970},
issn = {2296-858X},
abstract = {INTRODUCTION: Leukocyte telomere length is considered a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, and respiratory support), and mortality. However, the contribution of telomere length to post-COVID-19 syndrome (PCS) development is unclear.

AIM: This study aimed to evaluate the association between telomere shortening and the course of PCS in patients with type 2 diabetes (T2D) and to determine whether telomere length is linked to clinical phenotype, gender, and biological age.

MATERIALS AND METHODS: In this cross-sectional study, 66 T2D patients who had recovered from COVID-19 were enrolled. Patients were divided into two groups depending on PCS development: the PCS group (n = 44) and patients who did not develop PCS (n = 22) within 6 months after COVID-19 infection. Relative telomere length was determined using the standardized method proposed by Cawthon et al. A range of machine learning models was developed for PCS prediction. These models underwent training utilizing a cross-validation approach, as well as internal validation.

RESULTS: We observed a significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09 ± 0.19 and 1.28 ± 0.24; p = 0.001). In the sub-analysis, shorter telomeres were observed in female patients and patients of older age in both groups. The mean telomere length did not differ significantly among clinical phenotypes of PCS (p = 0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM), which achieved an AUC of 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly greater impact than other features.

CONCLUSION: Shorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.},
}

@article {pmid40947687,
year = {2025},
author = {Khodabandelu, S and Jahankhah, S and Shabestari, NM and Eghbal, Y and Khaleghi, S and Hajizadeh, A and Ghaheri, SZ and Jafari, M and Vosough, M and Rahmanian, M},
title = {The Association Between Telomere Length and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240360593250805102356},
pmid = {40947687},
issn = {1875-5666},
abstract = {INTRODUCTION: Studies have stated that there has been a close association between the telomere length (TL) and the incidence of non-alcoholic fatty liver disease (NAFLD). The goal of this report is to explore the possible association between TL and NAFLD.

METHODS: This study adhered to the PRISMA guidelines for systematic reviews. An extensive literature search was conducted in the Cochrane Library, CINAHL, Scopus, PubMed, and Web of Science. The "meta" package in the R programming language, version 4.3.1, was used for statistical analysis.

RESULTS: The meta-analysis of the included studies showed a pooled standard mean difference (SMD) of -0.25 (95% CI: -0.39 to -0.10), indicating shorter TL in NAFLD patients. Subgroup analyses revealed significant TL shortening in NAFLD patients with body mass index (BMI) <28 (SMD = -0.68, 95% CI: -0.96 to -0.39) and in case-control (-0.35, 95% CI: -0.51 to -0.20) and cohort studies (-0.68, 95% CI: -1.19 to -0.17). An odds ratio (OR) meta-analysis of six studies found that individuals with short TL had 1.72 times higher odds of NAFLD, which was statistically significant (95% CI: 1.23- 2.42, I2 = 85%). Excluding one study reduced heterogeneity (I2 = 37%) and increased the OR to 1.93 (95% CI: 1.45-2.56), confirming a strong association between short TL and NAFLD risk.

DISCUSSION: The findings suggest a potential link between shorter TL and NAFLD. The odds ratio analyses further emphasized the increased risk of NAFLD in individuals with short TL. Nevertheless, the residual heterogeneity highlights the need for further high-quality, standardized research.

CONCLUSION: Our findings supported the connection between reduced TL and NAFLD. Regardless of significant between-study diversity, the results remained consistent even after repeated sensitivity evaluations. Despite these findings, the high heterogeneity highlights the need for further well-designed studies to confirm TL as a reliable biomarker for NAFLD risk and progression.},
}

@article {pmid40936085,
year = {2025},
author = {Giffoni, FC and Gomes, TEC and de Souza, PN and Silva, PVE and Magno, LAV and Cândido, AL and Lasmar, MF and de Oliveira Neto, SG and Ferreira, MVL and Araujo, TMG and Dos Santos, LI and Chrcanovic, BR and Gomez, RS and Martins-Chaves, RR},
title = {Investigation of the Telomere Length in PERI-Implant Oral Mucosa Cells.},
journal = {Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jop.70061},
pmid = {40936085},
issn = {1600-0714},
support = {//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {BACKGROUND: The biological effects of dental implants on peri-implant tissues have been widely investigated. Recent reports of oral squamous cell carcinoma (OSCC) cases adjacent to dental implants have raised concerns regarding the potential impact of implant materials on cellular aging and oncogenic transformation. Telomeres, which protect chromosome ends, undergo progressive shortening and play a critical role in cellular senescence and tumorigenesis. However, the impact of dental implants on telomere length in peri-implant mucosa remains unclear.

OBJECTIVE: This study aimed to compare telomere length in mucosa adjacent to dental implants with that of gingival tissue associated with healthy teeth.

METHODS: A paired cross-sectional study was conducted with 16 patients who had dental implants for at least 1 year. Swabs were collected from the peri-implant mucosa and healthy gingival mucosa of the same patient. Telomere length was assessed using quantitative PCR, with the relative telomere-to-single-copy-gene ratio (T/C) calculated using the 2[-∆∆Cq] method.

RESULTS: Telomere length in the peri-implant mucosa was not significantly different from that in the healthy gingival mucosa (p = 0.117).

CONCLUSION: These findings suggest that dental implants do not alter telomere length in adjacent mucosal cells.},
}

@article {pmid40934081,
year = {2025},
author = {Dufourd, J and Huynh, THY and Sauzet, S and Lai, QH and Abagnale, F and Zitouni, S and Giraud-Panis, MJ and Urbach, S and Gilson, E and Tardat, M and Déjardin, J},
title = {TELS1 stabilizes t-loops independently of TRF2 and controls telomere length in pluripotent cells.},
journal = {Cell reports},
volume = {44},
number = {9},
pages = {116260},
doi = {10.1016/j.celrep.2025.116260},
pmid = {40934081},
issn = {2211-1247},
abstract = {Telomeric loops (t-loops) are thought to protect chromosome ends, with their stabilization generally requiring the shelterin protein TRF2. However, the mechanisms operating in pluripotent cells remain unknown. Here, we identify TELS1 as a TRF2-independent t-loop stabilizer in pluripotent cells. TELS1 binds single-stranded, G-rich telomeric DNA tracts likely present within duplex telomeric regions and promotes strand invasion in vitro, consistent with a direct role in t-loop formation. When targeted to telomeres in differentiated cells, TELS1 is able to substitute for TRF2 in making the t-loop, which partially protects from ATM activation. In TELS1-deficient pluripotent cells, telomeres lack t-loops but remain protected and become more accessible to telomerase, resulting in elongation. A genome-wide CRISPR screen identifies Ubr5 as essential for this tolerance. These findings validate the t-loop as an essential structure for end protection and uncover a telomere protection pathway unique to pluripotent cells that appears to function independently of shelterin.},
}

@article {pmid40930178,
year = {2025},
author = {Wen, DN and Hu, JH and Ji, T and Xiao, XY and Huang, CX and Zhang, JF and Feng, WB and Zheng, S and Xiong, ZY and Hou, CL},
title = {Alterations of telomere length and mitochondrial DNA copy number in depressive adolescents with non-suicidal self-injury.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {120268},
doi = {10.1016/j.jad.2025.120268},
pmid = {40930178},
issn = {1573-2517},
abstract = {BACKGROUND: NSSI among adolescents is highly prevalent and serves as a significant indicator of subsequent suicidal ideation and behaviors. Recent studies have demonstrated a connection between accelerated cellular aging and a range of psychiatric conditions. The present study explored whether depressive adolescents with NSSI exhibited alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNAcn), both critical markers of cellular aging.

METHODS: The study comprised 70 depressive adolescents with NSSI (84.3 % female) and 34 depressive adolescents without NSSI (61.8 % female). The TL and mtDNAcn were determined by calculating the ratio of telomere repeats to the single-copy gene β-globin, or by measuring the relative quantity of mtDNA compared to β-globin.

RESULTS: In this study, the NSSI group demonstrated significantly shorter TL than the non-NSSI group (P < 0.01). This difference persisted after controlling for age, family history, sex, suicidality, childhood maltreatment, depressive symptoms, and psychotic symptoms (P = 0.005). Furthermore, regression analysis showed that TL was considerably shorter in the female NSSI group than in the non-NSSI group after adjusting for age, family history, suicidality, childhood maltreatment, depressive symptoms, and psychotic symptoms (P < 0.001). After controlling for these variables, mtDNAcn was markedly reduced in the male NSSI group compared to the non-NSSI group (P < 0.001).

CONCLUSIONS: This work is, to our knowledge, the first to demonstrate that NSSI correlates with alterations in TL and mtDNAcn. These findings suggest that molecular pathways associated with aging may play a crucial role in the pathogenesis of NSSI.},
}

@article {pmid40930086,
year = {2025},
author = {Rivadeneira, DB and Thosar, S and Quann, K and Gunn, WG and Dean, VG and Xie, B and Parise, A and McGovern, AC and Spahr, K and Lontos, K and Barnes, RP and Bruchez, MP and Opresko, PL and Delgoffe, GM},
title = {Oxidative-stress-induced telomere instability drives T cell dysfunction in cancer.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.08.008},
pmid = {40930086},
issn = {1097-4180},
abstract = {The tumor microenvironment (TME) imposes immunologic and metabolic stresses sufficient to deviate immune cell differentiation into dysfunctional states. Oxidative stress originating in the mitochondria can induce DNA damage, most notably telomeres. Here, we show that dysfunctional T cells in cancer did not harbor short telomeres indicative of replicative senescence but rather harbored damaged telomeres, which we hypothesized arose from oxidative stress. Chemo-optogenetic induction of highly localized mitochondrial or telomeric reactive oxygen species (ROS) using a photosensitizer caused the accumulation of DNA damage at telomeres, driving telomere fragility. Telomeric damage was sufficient to drive a dysfunctional state in T cells, showing a diminished capability for cytokine production. Localizing the ROS scavenger GPX1 directly to telomeres reduced telomere fragility in tumors and improved the function of therapeutic T cells. Protecting telomeres through expression of a telomere-targeted antioxidant may preserve T cell function in the TME and drive superior responses to cell therapies.},
}

@article {pmid40926757,
year = {2025},
author = {Pott, J and Höing, AS and Volk, A and Well, L and Beier, F and Lebrecht, D and Harbaum, L and Klose, H and Oqueka, T},
title = {Telomere biology disorder associated lung disease- case report of a TERT gene variant as the cause of pleuroparenchymal fibroelastosis.},
journal = {Chronic respiratory disease},
volume = {22},
number = {},
pages = {14799731251370357},
pmid = {40926757},
issn = {1479-9731},
mesh = {Humans ; Genetic Testing ; *Lung Diseases, Interstitial/genetics ; *Telomerase/genetics ; Telomere/genetics ; *Telomere Shortening/genetics ; Tomography, X-Ray Computed ; },
abstract = {Case presentationDescription of a patient with a progressive destructive lung disease resembling pleuroparenchymal fibroelastosis, liver cirrhosis and bone marrow changes. Genetic workup identified a rare heterozygous coding variant in the TERT (telomerase reverse transcriptase) gene c.472 C>T; p.(Leu158Phe) and telomere length testing revealed significant telomere shortening, supporting the diagnosis of telomere biology disorder (TBD).DiscussionTBD is an underrecognized cause of interstitial lung disease (ILD). It is a heterogeneous disease that can affect different organs, including lungs, liver and bone marrow. Genetic testing in ILD is crucial for early diagnosis, risk assessment, and family screening. Identifying this variant enables targeted genetic testing for relatives, allowing preventive measures and lifestyle modifications.},
}

Humans
Genetic Testing
*Lung Diseases, Interstitial/genetics
*Telomerase/genetics
Telomere/genetics
*Telomere Shortening/genetics
Tomography, X-Ray Computed

@article {pmid40925232,
year = {2025},
author = {Tara, SA and Zekri, A and Sotoodehnejadnematalahi, F and Modarressi, MH},
title = {Aurora B inhibition induces polyploidy and mitotic catastrophe in HER2-amplified breast cancer: Telomere shortening as a potential anticancer mechanism of AZD1152-HQPA.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {191},
number = {},
pages = {118509},
doi = {10.1016/j.biopha.2025.118509},
pmid = {40925232},
issn = {1950-6007},
abstract = {Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy. However, its role in chromosome ploidy and telomere length maintenance in breast cancer remains insufficiently explored. In this study, we identified a significant association between Aurora B overexpression and poor prognosis exclusively in patients with HER2-amplified breast cancer. Treatment with AZD1152-HQPA, a selective Aurora B kinase inhibitor, significantly reduced cell viability and colony-forming potential, with a pronounced effect on HER2-amplified breast cancer cell lines. Importantly, we found that Aurora B inhibition is sufficient to induce polyploidy/multinucleation (8 N and 16 N), cellular enlargement, and mitotic catastrophe. Furthermore, we observed telomere shortening, downregulation of the human telomerase reverse transcriptase (hTERT) and TERRA (telomeric repeat-containing RNA), and a concomitant increase in ROS production following Aurora B inhibition and polyploidization. Mechanistically, we investigated the protein-protein interaction between Aurora B kinase and upstream regulators of hTERT. Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells.},
}

@article {pmid40923810,
year = {2025},
author = {Wang, Y and Zhang, J and Chang, K and Liu, S and Ji, J and Han, M and Wei, J},
title = {Relationship between biotransformation enzyme genes in polycyclic aromatic hydrocarbon metabolism, telomere length and missed abortion.},
journal = {International journal of environmental health research},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/09603123.2025.2557430},
pmid = {40923810},
issn = {1369-1619},
abstract = {The mechanism underlying the effects of Polycyclic aromatic hydrocarbons (PAHs) on missed abortion (MA) remains unclear. This study explored the relationship between PAHs exposure, telomere length (TL), metabolizing enzyme gene polymorphism, and MA in a case-control study with 253 pregnant women. A competitive enzyme-linked immunosorbent assay (ELISA) was used to quantify PAH-DNA adducts. The DNA was extracted from villi tissue for the analysis of TL using the real-time quantitative polymerase chain reaction (qPCR) method. Single nucleotide polymorphism (SNP) genotyping was performed using multiplex PCR amplification and high-throughput sequencing methods. The adjusted logistic regression model was used to reveal the relationship between PAH-DNA adducts, TL and MA pairs. The Generalized Multifactor Dimensionality Reduction (GMDR) was used to analyze gene-gene and gene-environment interactions. Results showed higher PAH-DNA adducts in the case group (P = 0.009), shorter TL in MA cases (Z = -4.02, P < 0.001), and a variant site in glutathione S-transferase M1 (GSTM1) (rs1065411) were associated with MA. Higher PAH-DNA adducts level was significantly associated with MA occurrence. Significant interactions were observed between GSTM1 gene and GSTM1 (rs1065411) and PAH-DNA adducts. These findings highlight the importance of PAHs exposure in MA etiology.},
}

@article {pmid40923756,
year = {2025},
author = {Sepšiová, R and Procházková, K and Červenák, F and Majerčík, D and Hanáková, K and Lattová, E and Hajikazemi, M and Zdráhal, Z and Virágová, S and Brzáčová, Z and Paeschke, K and Nosek, J and Tomáška, Ľ},
title = {Poly (ADP-ribose) polymerase in yeasts: characterization and involvement in telomere maintenance.},
journal = {Nucleic acids research},
volume = {53},
number = {17},
pages = {},
pmid = {40923756},
issn = {1362-4962},
support = {APVV-23-0056//Slovak Research and Development Agency/ ; APVV-19-0068//Slovak Research and Development Agency/ ; APVV 22-0144//Slovak Research and Development Agency/ ; //Ministry of Education/ ; 1/0031/24//Sport of the Slovak republic/ ; 1/0234/23//Sport of the Slovak republic/ ; 1R01ES031635-01/NH/NIH HHS/United States ; //Operation Program of Integrated Infrastructure/ ; //European Regional Development Fund/ ; //MEYS/ ; //CR/ ; //CEITEC institutional/ ; //CANTAR project/ ; Az. 10.21.1.027MN//Fritz Thyssen Foundation/ ; },
mesh = {*Telomere Homeostasis ; *Yarrowia/enzymology/genetics ; *Poly(ADP-ribose) Polymerases/metabolism/genetics/chemistry ; *Telomere/metabolism ; *Fungal Proteins/metabolism/genetics/chemistry ; Telomerase/metabolism/genetics ; },
abstract = {Poly (ADP-ribose) polymerases (PARPs) are enzymes catalyzing the post-translational addition of chains of ADP-ribose moieties to proteins. In most eukaryotic cells, their primary protein targets are involved in DNA recombination, repair, and chromosome maintenance. Even though this group of enzymes is quite common in both eukaryotes and prokaryotes, no PARP homologs have been described so far in ascomycetous yeasts, leaving their potential roles in this group of organisms unexplored. Here, we characterize Pyl1 protein of Yarrowia lipolytica as the first candidate of PARP in yeasts. We show that the expression of PYL1 gene is increased in mutants lacking either subunit of telomerase and identified several of its candidate protein targets in vivo. We demonstrate that Pyl1p is a functional PARP that undergoes auto-PARylation and PARylates YlKu70/80 complex. We also show that overexpression of PYL1 in Y. lipolytica cells results in dissociation of YlKu80 from telomeres in vivo, supporting the role of Pyl1p in telomere protection and maintenance. Based on our observations, we propose Pyl1p and its homologs identified in other yeast species represent a distinct class of PARPs, thus substantiating a more detailed investigation of their roles in these organisms.},
}

*Telomere Homeostasis
*Yarrowia/enzymology/genetics
*Poly(ADP-ribose) Polymerases/metabolism/genetics/chemistry
*Telomere/metabolism
*Fungal Proteins/metabolism/genetics/chemistry
Telomerase/metabolism/genetics

@article {pmid40913436,
year = {2025},
author = {Conklin, QA and Smith, DL and Dai, G and King, BG and Saron, CD and Lin, J},
title = {Remote Blood Collection for Telomere Length Measurement: Assessing the Impact of Sample Characteristics and Handling on DNA Quality and Assay Outcomes.},
journal = {American journal of human biology : the official journal of the Human Biology Council},
volume = {37},
number = {9},
pages = {e70128},
pmid = {40913436},
issn = {1520-6300},
support = {//Hershey Family Foundation/ ; //Yoga Science Foundation/ ; R24AG048024/AG/NIA NIH HHS/United States ; U01AG064785/NH/NIH HHS/United States ; //Mind and Life Institute/ ; R24 AG048024/AG/NIA NIH HHS/United States ; 4333//Fetzer Institute/ ; //Tom and Nancy Driscoll Foundation/ ; U01 AG064785/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Blood Specimen Collection/methods ; *DNA ; Male ; Female ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Adult ; *Telomere ; Aged ; Reproducibility of Results ; },
abstract = {BACKGROUND: Telomere length (TL) is a valuable marker of aging and stress that reflects both genetic and environmental influences. Quantitative PCR (qPCR) TL measurement is a powerful and cost-effective assay, especially in population studies with limited quantities of source material. Nevertheless, collecting and transporting high-quality blood samples can be logistically challenging, and research suggests that several preanalytical and analytical factors can influence the reliability and precision of the qPCR assay. Here we describe a procedure for collecting blood remotely in a large-scale study. We then assess the influence of various features of the samples, as well as their collection, transportation, and storage on DNA quality and TL assay outcomes.

METHOD: Participants used at-home collection kits to collect a few drops of whole blood in BD Microtainers during a baseline (n = 265) and 1-year follow-up (n = 178) assessment. DNA was extracted using a magnetic-bead method, and DNA yield, purity, and integrity were assessed. TL was measured using qPCR. To assess inter-assay variation, the coefficient of variation (CV) was calculated across repeated TL measurements (three runs) for each sample. When there was adequate material for duplicate extractions of DNA from the same blood samples, we calculated the intra-class correlation (ICC) of the resultant TL values to assess assay precision.

RESULTS: Our analyses revealed that as little as 50 μL of blood yielded sufficient DNA for highly precise TL measurement (ICC = 0.962, n = 365). Transportation time and an additional year of storage time at -80°C did not meaningfully affect DNA quality or assay outcomes. However, blood clotting was associated with longer telomere estimates, whereas greater temperature exposure was related to shorter telomere estimates.

CONCLUSIONS: We established that whole blood collected remotely in BD Microtainers can provide a valid sample source for qPCR TL measurement. We also outline important logistical considerations related to sample collection and handling and provide recommendations for researchers who want to use this method.},
}

Humans
*Blood Specimen Collection/methods
*DNA
Male
Female
Middle Aged
Real-Time Polymerase Chain Reaction
Adult
*Telomere
Aged
Reproducibility of Results

@article {pmid40909680,
year = {2025},
author = {Rowe, M and Tober, J and Ortiz, V and Smoom, R and Tzfati, Y and Speck, N and Kaestner, KH},
title = {Human length telomeres restrict the regenerative potential of hematopoietic stem cells in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909680},
issn = {2692-8205},
support = {R01 CA249929/CA/NCI NIH HHS/United States ; R01 DK139049/DK/NIDDK NIH HHS/United States ; R01 HL091724/HL/NHLBI NIH HHS/United States ; },
abstract = {Extremely short telomeres cause bone marrow failure in telomere biology disorder (TBDs) patients. Here, we employed the recently developed 'Telomouse' with human-length telomeres resulting from a single amino acid substitution in the helicase Rtel1 (Rtel1 [M492K/M492K]) to determine the effects of the short telomeres on the bone marrow and hematopoiesis. Under homeostatic conditions, Telomice have notably short telomeres but normal hematopoiesis. However, when forced to repopulate following repeated treatment with 5-fluoro-uracil or upon bone marrow transplantation into lethally irradiated mice, bone marrow progenitor cells are significantly depleted in Telomice compared to wild-type controls. This effect is associated with increased frequency of telomere repeat arrays too short to be detected by fluorescence in situ hybridization in the bone marrow of Telomice.},
}

@article {pmid40908429,
year = {2025},
author = {Al-Dulaimi, S and Thomas, R and Matta, S and Roberts, T},
title = {Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.},
journal = {Biogerontology},
volume = {26},
number = {5},
pages = {178},
pmid = {40908429},
issn = {1573-6768},
mesh = {Humans ; *Telomerase/metabolism/genetics ; Up-Regulation/drug effects ; *Telomere Homeostasis/drug effects ; Cell Line, Tumor ; *Telomere/drug effects/metabolism ; *Oligopeptides/pharmacology ; Female ; RNA, Messenger/metabolism ; Fibroblasts/drug effects ; Breast Neoplasms/genetics/enzymology ; Cell Line ; },
abstract = {Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mammalian cells. This happens through the induction of telomerase enzyme activity, resulting in the extension of telomere length. A strong link exists between telomere length and aging-related diseases. Therefore, telomeres are considered to be one of the biomarkers of aging, and increasing or maintaining telomere length may contribute to healthy aging and longevity. Epitalon has been the subject of several anti-aging studies however, quantitative data on the biomolecular pathway leading to telomere length increase, hTERT mRNA expression, telomerase enzyme activity, and ALT activation have not been extensively studied in different cell types. In this article, the breast cancer cell lines 21NT, BT474, and normal epithelial and fibroblast cells were treated with epitalon then DNA, RNA, and proteins were extracted. qPCR and Immunofluorescence analysis demonstrated dose-dependent telomere length extension in normal cells through hTERT and telomerase upregulation. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation. Only a minor increase in ALT activity was observed in Normal cells, thereby showing that it was specific to cancer cells. Our data suggests that epitalon can extend telomere length in normal healthy mammalian cells through the upregulation of hTERT mRNA expression and telomerase enzyme activity.},
}

Humans
*Telomerase/metabolism/genetics
Up-Regulation/drug effects
*Telomere Homeostasis/drug effects
Cell Line, Tumor
*Telomere/drug effects/metabolism
*Oligopeptides/pharmacology
Female
RNA, Messenger/metabolism
Fibroblasts/drug effects
Breast Neoplasms/genetics/enzymology
Cell Line

@article {pmid40908046,
year = {2025},
author = {Yu, J and Zhang, Y and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327492},
pmid = {40908046},
issn = {1468-2079},
abstract = {PURPOSE: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.

METHODS: We conducted a longitudinal cohort study involving 332 123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).

RESULTS: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95% CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95% CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (β=-0.141 µm, 95% CI: -0.267 to -0.016; β=-0.345 µm, 95% CI: -0.649 to -0.041, p<0.05).

CONCLUSIONS: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.},
}

@article {pmid40907145,
year = {2025},
author = {Goetz, SMM and Lucas, T and Finegood, E and Lin, J and Granger, D},
title = {Age and gender intersectionality among African Americans: Salivary uric acid is associated with shorter telomere length in younger adults and men.},
journal = {Psychoneuroendocrinology},
volume = {181},
number = {},
pages = {107588},
doi = {10.1016/j.psyneuen.2025.107588},
pmid = {40907145},
issn = {1873-3360},
abstract = {Age related diseases present disproportionately among African Americans and have been tied to broad social inequalities and accompanying stress. Yet, there is considerable variability among African Americans in susceptibility, highlighting potential connections to both intersectionality and stress-related biological processes. A growing body of research links exposure to racism and discrimination to telomere length (TL)-an indicator of biological aging that is increasingly implicated in explaining stress-related racial health disparities. However, few studies have examined links to accompanying stress processes that may precede TL shortening. This includes examining Uric Acid (UA), which growing evidence suggests may comprise a unique biological aspect of the acute stress response, with implications for both racial health disparities and within-race heterogeneity. In a secondary analysis of a sample of healthy African Americans (N = 103, 33 men; M age = 31.41 years), we assessed the relationship between salivary UA (sUA) and TL. With an eye towards within-group heterogeneity, we also considered the moderating role of age and gender. Our findings revealed a negative association between UA and TL that was most pronounced in African American men and among younger African Americans. We apply an intersectional lens to interpret these results, revealing that different intersections of identity operate through distinct mechanisms. Among men, UA consistently predicted shorter telomeres regardless of discrimination exposure, suggesting biological pathways may be primary. However, among women, the UA/TL relationship was moderated by discrimination-with UA positively predicting TL under low discrimination but showing negative associations under high discrimination conditions. These findings demonstrate that intersectionality operates through multiple pathways simultaneously, with some intersections characterized by biological vulnerabilities while others are defined by social moderation effects. Future research directions should consider the multifaceted influences of UA on TL, recognizing that different intersectional positions may require examination of distinct biological and social mechanisms including potential interventions targeting UA levels to mitigate age-related illnesses and address health disparities among African Americans. Additionally, future studies should examine how additional intersecting systems of oppression might moderate the relationship between UA and TL.},
}

@article {pmid40907117,
year = {2025},
author = {Hu, G and Yu, Y and Yin, Y and Yang, X and Yu, R and Xiang, Q},
title = {Impact of telomere length on autoimmune thyroid disease in Europeans: insights from Mendelian randomization.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100765},
doi = {10.1016/j.clinsp.2025.100765},
pmid = {40907117},
issn = {1980-5322},
abstract = {OBJECTIVE: This study aimed to investigate the causal relationship between Telomere Length (TL) and Autoimmune Thyroid Disease (AITD) in Europeans using Mendelian Randomization (MR).

METHODS: Single nucleotide polymorphisms associated with TL and AITD were obtained from genome-wide association studies. MR analysis was conducted using inverse variance weighted as the primary method. Cochran's Q test and leave-one-out sensitivity analysis were employed to assess heterogeneity and robustness, respectively.

RESULTS: TL was significantly associated with reduced genetic susceptibility to Graves' Disease (GD) in Europeans (Odds Ratio [OR = 0.776], 95 % Confidence Interval [95 %CI 0.625-0.964]; p = 0.022). However, no association was found between TL and Autoimmune Thyroiditis (AIT) (OR = 1.474, 95 % CI 0.870-2.497; p = 0.149). Cochran's Q test and leave-one-out sensitivity analysis confirmed that the findings were free of heterogeneity and robust.

CONCLUSION: MR analysis revealed that TL shortening is associated with increased genetic susceptibility to GD in Europeans, but no such association was observed for AIT. Further research is needed to elucidate the mechanisms through which TL influences AITD.},
}

@article {pmid40905409,
year = {2025},
author = {He, H and Yang, X and Wang, K and Ye, Q},
title = {Oxidative DNA damage may promote the development of endometriosis by activating telomerase and extending telomere length: a meta-analysis.},
journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/1354750X.2025.2557452},
pmid = {40905409},
issn = {1366-5804},
abstract = {OBJECTIVE: To investigate the associations between oxidative DNA damage biomarkers [levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), telomere length (TL), human telomerase reverse transcriptase (hTERT), telomerase activity (TA) and polymorphisms of human 8-oxoguanine glycosylase 1 (hOGG1) or X-ray repair cross-complementing group 4 (XRCC4)] and endometriosis (EMT) by a meta-analysis.

METHODS: Five databases were searched until August 2024. Stata 15.0 was used to estimate pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CIs).

RESULTS: Forty-two studies were included. Overall meta-analysis revealed significantly elevated 8-OHdG (SMD = 1.84; 95%CI = 1.29 - 2.39), TA (SMD = 3.03; 95%CI = 2.07 - 4.00) and hTERT (SMD = 2.55; 95%CI = 1.55 - 3.55) in EMT women compared to controls. Women carrying GG genotype (vs GC + CC: OR = 1.34; 95%CI = 1.00 - 1.78) of hOGG1 rs1052133, TT genotype (vs TG + GG: OR = 2.67; 95%CI = 1.63 - 4.38) and T allele (vs G: OR = 3.49; 95%CI = 2.27 - 5.35) of XRCC4 rs6869366 had a higher risk of developing EMT. Subgroup and trim-and-fill analyses indicated longer TL was a risk factor for EMT.

CONCLUSIONS: 8-OHdG, TA, hTERT, TL, rs1052133 and rs6869366 represent potential prediction biomarkers and treatment targets for EMT.},
}

@article {pmid40903918,
year = {2025},
author = {Lowran, K and Campbell, L and Cismas, E and Wu, CG},
title = {Domain-Specific DNA Binding Activities of BRCA1 Reveal Substrate Preferences for Homologous Recombination and Telomere Regulation.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00333},
pmid = {40903918},
issn = {1520-4995},
abstract = {BRCA1 is a crucial component of homologous recombination (HR), a high-fidelity pathway for repairing double-stranded DNA breaks (DSBs) in human cells. The central region of the BRCA1 protein contains two putative DNA binding domains (DBDs), yet their relative substrate specificities and functional contributions to HR remain unclear. Here, we characterized the DNA binding properties of DBD1 (amino acids 330-554), DBD2 (amino acids 894-1057), and BRCA1 C-terminal (BRCT) repeats using biolayer interferometry. Affinities were determined for single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex (G4) DNA. DBD2 exhibited strong and nearly identical binding to all three substrates (Kd = ∼35-44 nM), while the BRCT also bound to each structure similarly, but with lower affinity (Kd = ∼149-184 nM). In contrast, DBD1 showed a distinct preference for dsDNA, binding approximately 2-fold tighter compared to ssDNA or G4. These findings support a model in which BRCA1 uses modular DNA binding domains to recognize diverse repair targets; DBD2 serves as a primary anchor to associate with a broad range of DNA structures with BRCT contributing to the contacts. DBD1 acts as the determinant of DNA structure-specific localization that may help direct BRCA1 to DSB sites during HR or to noncanonical elements such as chromatin and telomeres. These insights lay the groundwork for future studies examining how cancer-associated variants affect the DNA binding and repair phenotypes of BRCA1 and may inform the interpretation of variants of unknown clinical significance.},
}

@article {pmid40901206,
year = {2025},
author = {Luo, S and Chai, J and Cai, Y and Ding, L and Tang, S},
title = {Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {5551-5556},
pmid = {40901206},
issn = {2049-0801},
abstract = {BACKGROUND: The relationship between telomere length and breast diseases remains unclear, with conflicting evidence for breast cancer. Using an innovative genetic approach, we were the first to comprehensively assess their bidirectional causal relationship.

METHODS: Telomere length, breast cancer, benign neoplasm of breast, and breast inflammation were extracted from the genome-wide Association study (GWAS) database as the basis for large-scale population studies. The interaction of telomere length and breast diseases as exposure and outcome factors was analyzed by Mendelian randomization (MR).

RESULTS: When telomere length was used as an exposure factor and breast diseases as an outcome, the P value of MR was less than 0.05. Breast cancer (odds ratio (OR) = 1.130, 95% confidence interval (CI) = 1.047-1.219, P = 0.0016), benign neoplasm of breast (OR = 1.002, 95%CI = 1.001-1.004, P = 0.0007) and breast inflammation (OR = 1.487, 95%CI = 1.008-2.191, P = 0.0453). When breast diseases were taken as an exposure factor and telomere length was taken as an outcome, the P value of MR between breast cancer, benign neoplasm of breast, and telomere length was greater than 0.05, and breast inflammation could not be calculated by MR.

CONCLUSION: Telomere length is a risk factor for breast diseases, and longer telomeres increase the risk of breast cancer, benign neoplasm of breast, and breast inflammation. However, the reverse study showed no causal association between breast cancer, benign neoplasm of breast and telomere length, and the causal association between breast inflammation and telomere length was not clear. Moreover, further studies are needed to validate our findings in non-European populations.},
}

@article {pmid40900359,
year = {2025},
author = {Jaiswal, RK and Garibo Domingo, T and Grunchec, H and Singh, K and Pirooznia, M and Elhaik, E and Cohn, M},
title = {Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {19},
pmid = {40900359},
issn = {1432-0983},
mesh = {*Telomerase/genetics/metabolism ; *Telomere/genetics ; *Saccharomycetales/genetics ; *Telomere Homeostasis/genetics ; Telomere-Binding Proteins/genetics/metabolism ; *Telomere Shortening/genetics ; },
abstract = {Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast Naumovozyma castellii, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in N. castellii ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to all telomeres. Genome sequencing of the wild-type strain revealed variants of the TelKO element, differing in their lengths, and separate ALT strains are maintained by spreading of distinct TelKO element variants. Although short uniform telomere structures are predominant, sporadic telomere lengthening events occur by addition of long repeated arrays of TelKO elements. The telomere-binding protein Rap1 can bind to TelKO sequences in vitro, indicating a functional role of TelKO elements in providing stability to shortened ALT telomeres. Our results suggest that stable maintenance and telomere functionality may be achieved by incorporating the distal subtelomeric TelKO sequences into the telomeric chromatin cap.},
}

*Telomerase/genetics/metabolism
*Telomere/genetics
*Saccharomycetales/genetics
*Telomere Homeostasis/genetics
Telomere-Binding Proteins/genetics/metabolism
*Telomere Shortening/genetics

@article {pmid40894009,
year = {2025},
author = {Jain, N and Luo, J and Yang, Y and Aschebrook-Kilfoy, B and Ahsan, H and Chen, L and Pierce, B},
title = {Determinants of chromosome-specific telomere lengths among 2,573 All of Us participants.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7293781/v1},
pmid = {40894009},
issn = {2693-5015},
abstract = {Telomeres are DNA-protein structures that protect chromosome ends. The DNA component of telomeres shortens as cells divide, and telomere length (TL) is a key biomarker of aging and disease risk. Most previous studies in humans of TL have analyzed average TL; thus, our knowledge of TL variability across chromosome arms remains limited. The availability of long-read whole-genome sequencing (lrWGS) data has enabled the development of computational methods to measure chromosome-specific TL (csTL). We generated lrWGS-based csTLs for > 2,500 All of Us participants and characterized variability in csTL attributable to individuals, chromosome arms, participant characteristics, and technical factors. We found that TL varies by chromosome arm (9.1% of the variance in csTL), mirroring patterns observed in prior studies and highlighting the potential for chromosome-specific mechanisms of TL regulation. Substantial variance in csTL (8.9%) was attributable to individual, independent of age, supporting the hypothesis that individuals are endowed with short or long TL in early development, which is maintained throughout life. While age is inversely associated with TL across all arms, the strength of the association varied, with longer arms showing stronger associations. We demonstrate that csTL estimates can be used to estimate disease associations at individual telomeres, including outlying values in the csTL distribution. Our work identifies lrWGS quality metrics that impact csTL estimation, providing a framework to guide future studies. This study demonstrates the utility of lrWGS data for csTL profiling in population cohorts. Larger studies of csTL are needed to advance our understanding of telomeres in aging and disease.},
}

@article {pmid40893773,
year = {2025},
author = {Bansal, A and Phogat, P and Kukreti, S},
title = {Na[+] selective structural switch from an intramolecular triplex to tetrad stabilised by non-canonical mispairs in double repeat of Arabidopsis thaliana telomere (T3AG3)2.},
journal = {Biochemistry and biophysics reports},
volume = {43},
number = {},
pages = {102203},
pmid = {40893773},
issn = {2405-5808},
abstract = {DNA is polymorphic, as with four nucleobases, it can be configured in a number of secondary structures. The four-stranded DNA structures consisting of G-tetrads have especially been intriguing because of their proven existence in human cells. Due to the high prevalence of putative G-quadruplex-forming sequence motifs in the human genome, scientists in recent years have highlighted the potential of exploiting these exotic structures for targeted therapies for various cancers. G-quadruplexes are the most common and well-studied arrangements of four guanines; however, other possible non-canonical arrangements of nucleobases have also been reported. Herein, using Gel electrophoresis, Circular Dichroism, UV & CD-thermal denaturation methods, and NMR, we suggested that a double repeat of Arabidopsis thaliana telomere (T3AG3)2 shows a structural switch from a non-canonical intramolecular triplex to a non-conventional tetrad other than an antiparallel G-quadruplex. This transition is mediated by increasing Na[+] cation concentration from 0.1 M to 1.0 M, and the tetrad is fairly stabilised by a hydrogen-bonded cyclic array of non-canonical/mismatch base pairs (G∗G, G∗T, and T∗T). Intriguingly, such a structural transition was not manifested in the presence of K[+] ions. To the best of our knowledge, such a cation-specific non-canonical structural switch, in a telomeric sequence, has not been proposed to date.},
}

@article {pmid40891961,
year = {2025},
author = {Nasiri, L and Vaez-Mahdavi, MR and Ghazanfari, T and Hassanpour, H and Kaboudanian-Ardestani, S},
title = {Expression of telomere length and shelterin genes in men and women leukocytes and their correlations with lipid peroxidation in sulfur mustard gas intoxication.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/01480545.2025.2553203},
pmid = {40891961},
issn = {1525-6014},
abstract = {Sulfur mustard (SM), a chemical warfare agent, inflicts severe acute and chronic health effects. This study investigates the impact of SM-induced oxidative stress on telomere length (TL) and shelterin gene expression, which are crucial for telomere maintenance in exposed veterans. This study involved SM-exposed veterans and non-exposed controls. The SM-exposed group was divided into three subgroups based on exposure severity (severe, mild, and asymptomatic) and gender. Leukocyte TL, transcript of shelterin genes (TPP1, POT1, TIN2, TRF1, TRF2, RAP1), and plasma MDA were measured. TL was decreased in the SM-exposed group compared to the non-exposed group, while the MDA level was increased. The SM-exposed group showed lower expression of TIN2, TRF2, and the composite shelterin genes compared to the control group. In the SM-exposed subgroups, TL, TRF2 transcript, and composite shelterin gene expression were reduced compared to the non-exposed group, while the MDA levels were significantly increased. There are negative correlations between MDA and both TIN2/TRF2 expression and TL, and positive correlations between TL and composite shelterin gene expression. In the gender comparison, there were different effects of SM toxicity on TIN2, TPP1, TRF2, and the composite of shelterin gene expression between SM-exposed men and women. SM-exposed men had significantly higher MDA levels, while women showed no significant change. Also, there was no difference between non-exposed men and women. It is concluded that SM exposure increases lipid peroxidation, shortens telomeres, and alters shelterin genes in a gender-specific manner, suggesting accelerated biological aging as a delayed toxic effect.},
}

@article {pmid40884660,
year = {2025},
author = {M'kacher, R and Colicchio, B and Junker, S and Schabat, S and Belaiba, R and Sontos, L and Heidingsfelder, L and Najar, W and Plesch, A and Voisin, P and Dieterlen, A and Jeandidier, E and Carde, P},
title = {DNA Damage, Telomere and Centromere Dysfunction in Chromothripsis Rearrangements.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2968},
number = {},
pages = {441-455},
pmid = {40884660},
issn = {1940-6029},
mesh = {Humans ; *Chromothripsis ; *Telomere/genetics/metabolism ; *Centromere/genetics/metabolism ; *DNA Damage ; Neoplasms/genetics ; Chromosomal Instability ; Genomic Instability ; },
abstract = {The analysis of the origin of chromothripsis, catastrophic chromosomal rearrangements, has provided exceptional insights into various aspects of tumor progression and genetic disorders. Findings in chromothripsis have not only enhanced our understanding of genomic instability mechanisms, but also reshaped our views on chromosome mechanics. To date, the major mechanisms of chromothripsis described involve the incorporation of micronuclei into the primary nucleus and telomere crisis through the formation of dicentric chromosomes. Here, we reevaluated the impact of telomere and centromere sequences in the formation of micronuclei and anaphase bridges in cancer patients using our high throughput technique for the detection of telomere and centromere dysfunction and chromosomal instability biomarkers. We also discuss the emerging potential of exploiting telomere and centromere dysfunction combined with DNA damage as prognostic biomarkers and tools for personalized patient management.},
}

Humans
*Chromothripsis
*Telomere/genetics/metabolism
*Centromere/genetics/metabolism
*DNA Damage
Neoplasms/genetics
Chromosomal Instability
Genomic Instability

@article {pmid40879844,
year = {2025},
author = {Zhao, X and Shi, Y and Tang, M},
title = {Exploring the mediating role of telomere length in the association between physical activity and bone mineral density.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {263},
pmid = {40879844},
issn = {1720-8319},
mesh = {Humans ; *Bone Density/genetics/physiology ; *Exercise/physiology ; Female ; Middle Aged ; Male ; Aged ; *Telomere ; *Telomere Shortening ; Nutrition Surveys ; Osteoporosis/genetics ; DNA Methylation ; Telomere Homeostasis ; },
abstract = {BACKGROUND: Physical activity may mitigate osteoporosis progression by modulating telomere shortening processes.

AIMS: To explore the mediating role of telomere length (TL) in the relationship between physical activity and bone mineral density (BMD).

METHODS: This study enrolled 2,394 participants aged 50 years and older from the U.S. National Health and Nutrition examination Surveys. TL was measured by quantitative polymerase chain reaction (qPCR) method (TeloMean) and DNA methylation data (HorvathTelo), and accelerated telomere attrition was assessed through residual-based indices of TeloMeanAccel and HorvathTeloAccel. Physical activity was assessed via questionnaire and BMD was measured at multiple body sites. Multiple linear regression models were utilized to evaluate associations between TL metrics, physical activity, and BMD. Mediation analysis, restrict cubic spline (RCS) modeling, subgroup analyses and sensitivity analyses were further conducted.

RESULTS: After adjusting for covariates, TL metrics of TeloMean and HorvathTelo were found significantly positive correlations with BMD. HorvathTeloAccel, reflecting accelerated telomere shortening, also exhibited significant association with BMD. Physical activity demonstrated a significant positive association with total BMD (β = 0.046, 95%CI: 0.004-0.088). Mediation analysis revealed that TeloMean and HorvathTelo accounted for 4.78% and 20.86% of the total effect of physical activity on BMD, respectively, while HorvathTeloAccel explained 5.24% of the observed association.

CONCLUSION: Reduced physical activity and accelerated telomere attrition were related with BMD decline, and TL partially mediated the association. These findings suggest that enhancing physical activity could mitigate telomere shortening and promote bone health.},
}

Humans
*Bone Density/genetics/physiology
*Exercise/physiology
Female
Middle Aged
Male
Aged
*Telomere
*Telomere Shortening
Nutrition Surveys
Osteoporosis/genetics
DNA Methylation
Telomere Homeostasis

@article {pmid40880134,
year = {2025},
author = {Yuan, J and Li, J and Yong, J and Liao, X and Guo, H and Niu, Y},
title = {A telomere-to-telomere genome assembly of koi carp (Cyprinus carpio) using long reads and Hi-C technology.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40880134},
issn = {2047-217X},
support = {//Suxin Koi Farm/ ; },
mesh = {*Carps/genetics ; Animals ; *Genome ; *Telomere/genetics ; Genomics/methods ; Molecular Sequence Annotation ; },
abstract = {BACKGROUND: The common carp (Cyprinus carpio) is a key species in global freshwater aquaculture. One of its variants, the koi carp, is particularly prized for its aesthetic appeal. However, lacking a high-quality genome has limited genetic research and breeding efforts for common carp and koi carp.

FINDINGS: This study presents a gap-free genome for the Taisho Sansyoku koi carp strain (C. carpio). The assembly achieved a total size of 1,555.86 Mb with a contig N50 of 30.45 Mb, comprising 50 gap-free pseudochromosomes ranging in length from 20.70 to 49.02 Mb. The BUSCO completeness score reached 99.20%, and the Genome Continuity Inspector score was 85.82, indicating high genome integrity and accuracy. Notably, 83 out of 100 telomeres were detected, resulting in 33 chromosomes possessing complete telomeres. Comparative genomic analysis showed that the expanded gene families and unique genes play essential roles in various biological traits, such as energy metabolism, endocrine regulation, cell proliferation, and immune response, potentially related to multiple metabolic diseases and health conditions. The positively selected genes are linked to various biological processes, such as the metalloendopeptidase activity, which plays a significant role in the central nervous system and is associated with diseases.

CONCLUSIONS: The koi carp genome assembly (CC 4.0) fills a critical gap in understanding common carp's biology and adaptation. It provides an invaluable resource for molecular-guided breeding and genetic enhancement strategies, underscoring the importance of common carp and koi carp in aquaculture and ecological research.},
}

*Carps/genetics
Animals
*Genome
*Telomere/genetics
Genomics/methods
Molecular Sequence Annotation

@article {pmid40878745,
year = {2025},
author = {Li, W and Liang, H and Sun, J and Zhang, X and He, Q and Zhou, P and Huo, D},
title = {A Near Telomere-To-Telomere Genome Assembly and Graph-Based Pangenome of Tartary Buckwheat (Fagopyrum tataricum).},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70333},
pmid = {40878745},
issn = {1467-7652},
support = {2023ZD04076//Biological Breeding-National Science and Technology Major Project/ ; TYSGJ202201//Critical Talent Workstation Project/ ; 202203021222244//Basic Research Program of Shanxi Province/ ; },
}

@article {pmid40877435,
year = {2025},
author = {McLoughlin, MA and Cheloor Kovilakam, S and Dunn, WG and Gu, M and Tobin, J and Pershad, Y and Williams, N and Leongamornlert, D and Dawson, K and Bond, L and Marando, L and Wen, S and Wilson, R and Valenzano, G and Symeonidou, V and Rak, J and Damaskou, A and Gozdecka, M and Liu, X and Barcena, C and Nomdedeu, J and Costeas, P and Dimitriou, ID and Fiorillo, E and Orrù, V and de Almeida, JG and McKerrell, T and Cullen, M and Mohorianu, I and Foukaneli, T and Warren, AJ and Wong, C and Follows, G and Godfrey, AL and Gudgin, E and Cucca, F and McKinney, E and Baxter, EJ and Gerstung, M and Mitchell, J and Wiseman, D and Bick, AG and Fabre, M and Quiros, PM and Nangalia, J and Kar, S and Vassiliou, GS},
title = {Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40877435},
issn = {1546-1718},
support = {102160/B/13/Z//Wellcome Trust (Wellcome)/ ; CTRQQR-2021\100012//Cancer Research UK (CRUK)/ ; },
abstract = {The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454,098 UK Biobank participants, we find that, unlike most CH subtypes, splicing-factor-mutant CH is more common in those with shorter genetically predicted telomeres, as is CH with mutations in PPM1D and the TERT gene promoter. We go on to show that telomere attrition becomes an instrument for clonal selection in advanced age, with splicing factor mutations 'rescuing' HSCs from critical telomere shortening. Our findings expose the lifelong influence of telomere maintenance on hematopoiesis and identify a potential shared mechanism through which different splicing factor mutations drive leukemogenesis. Understanding the mechanistic basis of these observations can open new therapeutic avenues against splicing-factor-mutant CH and hematological or other cancers.},
}

@article {pmid40877081,
year = {2025},
author = {Karimi, B and Nabizadeh Nodehi, R and Yunesian, M},
title = {Retraction notice to "Serum level of PCBs and OCPs and leukocyte telomere length among adults in Tehran, Iran" [Chemosphere 248, June 2020, 126092].},
journal = {Chemosphere},
volume = {},
number = {},
pages = {144635},
doi = {10.1016/j.chemosphere.2025.144635},
pmid = {40877081},
issn = {1879-1298},
}

@article {pmid40872982,
year = {2025},
author = {Lim, J and Kim, J and Abdeahad, H and Hall, SA and Lesniewski, LA and Donato, AJ},
title = {Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone Aortic Regions.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70196},
doi = {10.1111/acel.70196},
pmid = {40872982},
issn = {1474-9726},
support = {R01 AG060395/NH/NIH HHS/United States ; R01 AG048366/NH/NIH HHS/United States ; T32 HL007576/NH/NIH HHS/United States ; T32 HL139451/NH/NIH HHS/United States ; I01 BX004492/BX/BLRD VA/United States ; },
abstract = {Cellular senescence is a state of persistent cell cycle arrest and is a critical contributor to arterial aging. The primary drivers of cellular senescence are the DNA damage response (DDR) and telomere dysfunction, which is induced by increasing exposure to DNA-damaging stimuli such as atheroprone shear stress. While late-life aerobic exercise is an effective intervention to mitigate arterial aging, its specific impact on the DDR and telomere dysfunction is unknown and may not show uniform benefits across aortic regions subjected to atheroprone and non-atheroprone shear stress. This study investigates the influence of late-life aerobic exercise on DDR and telomere dysfunction in endothelial cells (EC) and vascular smooth muscle cells (VSMC) within the aortic regions exposed to distinct shear stress patterns. Old male C57BL6 mice were randomly assigned to a negative control (NC) group and habitual voluntary wheel running (VWR) groups for 16 weeks. The habitual VWR groups were further categorized into low (LR), moderate (MR), and high running (HR) groups based on their daily running distance throughout the intervention. EC and VSMC DDR and telomere dysfunction in NC, LR, and MR groups were comparable across the aortic regions. Interestingly, EC DDR and telomere dysfunction were mitigated in the non-atheroprone aortic regions in HR, but not in VSMC. These improvements were independent of telomere length. Collectively, these data provide evidence that late-life aerobic exercise selectively mitigates DDR and telomere dysfunction in ECs within non-atheroprone aortic regions, rather than atheroprone aortic regions, in an exercise volume-dependent manner, independent of telomere length.},
}

@article {pmid40870925,
year = {2025},
author = {Moustakli, E and Grigoriadis, T and Stavros, S and Potiris, A and Zikopoulos, A and Gerede, A and Tsimpoukis, I and Papageorgiou, C and Louis, K and Domali, E},
title = {Artificial Intelligence in Assessing Reproductive Aging: Role of Mitochondria, Oxidative Stress, and Telomere Biology.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {16},
pages = {},
pmid = {40870925},
issn = {2075-4418},
abstract = {Fertility potential ever more diminishes due to the complex, multifactorial, and still not entirely clarified process of reproductive aging in women and men. Gamete quality and reproductive lifespan are compromised by biologic factors like mitochondrial dysfunction, increased oxidative stress (OS), and incremental telomere shortening. Clinically confirmed biomarkers, including follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), are used to estimate ovarian reserve and reproductive status, but these markers have limited predictive validity and an incomplete representation of the complexity of reproductive age. Recent advances in artificial intelligence (AI) have the capacity to address the integration and interpretation of disparate and complex sets of data, like imaging, molecular, and clinical, for consideration. AI methodologies that improve the accuracy of reproductive outcome predictions and permit the construction of personalized treatment programs are machine learning (ML) and deep learning. To promote fertility evaluations, here, as part of its critical discussion, the roles of mitochondria, OS, and telomere biology as latter-day biomarkers of reproductive aging are presented. We also address the current status of AI applications in reproductive medicine, promises for the future, and applications involving embryo selection, multi-omics set integration, and estimation of reproductive age. Finally, to ensure that AI technology is used ethically and responsibly for reproductive care, model explainability, heterogeneity of data, and other ethical issues remain as residual concerns.},
}

@article {pmid40868898,
year = {2025},
author = {Vakonaki, E and Vitiadou, MT and Panteris, E and Tzatzarakis, M and Tsatsakis, A and Hatzidaki, E},
title = {Maternal Lifestyle During Pregnancy and Its Influence on Offspring's Telomere Length.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {40868898},
issn = {2075-1729},
abstract = {Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring's TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring's TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors-including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality-remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes.},
}

@article {pmid40868226,
year = {2025},
author = {Diaconu, M and Olaru, F and Abu-Awwad, A and Abu-Awwad, SA and Dragomir, T and Sacarin, G and Pilut, NC and Sorop, B and Bicu, M and Nitu, R},
title = {The Influence of Maternal Inflammatory Status on Fetal Telomere Length at Birth.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868226},
issn = {2227-9059},
support = {without a specific grant number//This research was funded by "Victor Babes" University of Medicine and Pharmacy, Timisoara/ ; },
abstract = {Background/Objectives: Fetal telomere length (FTL) at birth is considered a key marker of early biological aging and future disease risk. While chronic inflammation is known to accelerate telomere attrition in adults, limited evidence exists on how maternal inflammation during pregnancy impacts FTL. This study aimed to investigate the association between maternal systemic inflammatory status in late pregnancy and FTL at birth. Methods: We conducted a prospective cohort study including 150 clinically healthy pregnant women recruited in the third trimester. Participants were stratified post hoc into an inflammation group (n = 67) and a control group (n = 83) based on circulating inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), TNF-α, and IL-10. Umbilical cord blood was collected at birth, and telomere length was quantified using real-time PCR. Correlation and multivariable linear regression analyses were performed to evaluate associations between maternal inflammation and FTL. Results: Mothers in the inflammation group had significantly elevated hsCRP, IL-6, and TNF-α levels, and lower IL-10 concentrations. FTL was significantly shorter in this group compared to the controls. Unlike previous investigations that relied on single pro-inflammatory markers, our study tests a composite immune-balance index (IL-6/IL-10 ratio) together with hsCRP in a prospectively followed cohort of clinically healthy pregnancies. Using its correlation coefficient, the IL-6/IL-10 ratio alone explained approximately 28% of the total variance in fetal telomere length-almost double the variance captured by IL-6 assessed in isolation. IL-6 and hsCRP emerged as independent negative predictors of FTL in multivariable models (β = -0.37 and -0.29, respectively). The IL-6/IL-10 ratio showed the strongest inverse correlation with FTL (r = -0.53, p < 0.001). Conclusions: Subclinical systemic inflammation in late pregnancy is independently associated with shorter fetal telomere length at birth, highlighting maternal immune imbalance (especially IL-6/IL-10 ratio) as a modifiable determinant of early biological aging. These findings underscore the need to consider maternal inflammatory profiling in pregnancy as a potential target for early-life preventive strategies.},
}

@article {pmid40867830,
year = {2025},
author = {Valeanu, A and Margina, D and Moreno-Villanueva, M and Blasco, M and Sikora, E and Mosieniak, G and Capri, M and Breusing, N and Bernhardt, J and Schön, C and Toussaint, O and Debacq-Chainiaux, F and Grubeck-Loebenstein, B and Weinberger, B and Fiegl, S and Gonos, ES and Hervonen, A and Slagboom, EP and de Craen, A and Dollé, MET and Jansen, EHJM and Mocchegiani, E and Giacconi, R and Piacenza, F and Malavolta, M and Weber, D and Stuetz, W and Grune, T and Franceschi, C and Bürkle, A and Gradinaru, D},
title = {Causal Inference Approaches Reveal Associations Between LDL Oxidation, NO Metabolism, Telomere Length and DNA Integrity Within the MARK-AGE Study.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080933},
pmid = {40867830},
issn = {2076-3921},
abstract = {Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35-75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.},
}

@article {pmid40867046,
year = {2025},
author = {Smoom, R and Lichtental, D and Kaestner, KH and Tzfati, Y},
title = {The house mouse maintains constant telomere length throughout life.},
journal = {Nucleic acids research},
volume = {53},
number = {16},
pages = {},
doi = {10.1093/nar/gkaf830},
pmid = {40867046},
issn = {1362-4962},
support = {2071/18//Israel Science Foundation/ ; 1342/23//Israel Science Foundation/ ; R37-DK053839/DK/NIDDK NIH HHS/United States ; R01-CA249929/DK/NIDDK NIH HHS/United States ; //Israel-UK-Palestine GROWTH Fellowship/ ; 1342/23//ISF/ ; },
mesh = {Animals ; Mice ; *Telomere Homeostasis/genetics ; *Telomere/genetics/metabolism ; *Aging/genetics ; Telomerase/metabolism/genetics ; Male ; Telomere Shortening ; Leukocytes/metabolism ; Female ; },
abstract = {Telomeres protect the chromosome ends from deleterious DNA damage response and repair activities. In humans, telomerase maintains telomere length in germ and stem cells, but not in most somatic cells. Consequently, telomeres shorten with cell division and age, limiting cell proliferation and protecting against cancer. When telomeres become critically short, they may also cause senescence, inflammation, and organ failure, which are major drivers of aging. Therefore, maintaining an optimal, age-appropriate telomere length is crucial for healthy aging. In the house mouse, Mus musculus, telomerase is active in most somatic tissues, yet its long telomeres were thought to shorten rapidly with age. We have followed telomere length over age in blood and tail of wild-type M. musculus and in two engineered mouse strains with shorter telomeres (Telomouse and HHS mouse). We also measured the precise length of single telomeres in blood leukocytes of these mouse strains by a long-read nanopore sequencing method, NanoTelSeq. We show that telomeres in blood and tail of these three mouse strains do not shorten with age. We conclude that M. musculus maintains long telomeres in blood and tail throughout life, excluding the possibility that global telomere shortening in these tissues contribute to aging-associated phenotypes.},
}

Animals
Mice
*Telomere Homeostasis/genetics
*Telomere/genetics/metabolism
*Aging/genetics
Telomerase/metabolism/genetics
Male
Telomere Shortening
Leukocytes/metabolism
Female

@article {pmid40866587,
year = {2025},
author = {DePinho, RA},
title = {Telescopes, telomeres and turning points.},
journal = {Nature cancer},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43018-025-01024-y},
pmid = {40866587},
issn = {2662-1347},
}

@article {pmid40862088,
year = {2025},
author = {Bhatt, SP and Pandey, S and Misra, A},
title = {Independent Effects of Vitamin D on Leukocyte Telomere Length and Activity: An RCT in Asian Indian Women With Prediabetes.},
journal = {Journal of the Endocrine Society},
volume = {9},
number = {9},
pages = {bvaf124},
pmid = {40862088},
issn = {2472-1972},
abstract = {INTRODUCTION: Prediabetes is increasing in India and progresses rapidly to type 2 diabetes. The impact of vitamin D3 supplementation on telomerase activity and leukocyte telomere length (LTL) among people with prediabetes has been poorly researched.

RESEARCH DESIGN AND METHODS: In this 18-month prospective trial, we enrolled 121 women with prediabetes and randomized them into intervention (vitamin D3 supplementation, n = 61) and placebo (n = 60) groups. LTL and telomerase activity were measured.

RESULTS: In the current study, LTL and telomerase activity were assessed at visit 1 (week 0), visit 2 (week 52), and visit 3 (week 78). LTL increased significantly in the intervention group by week 52 (P = .004) and became more pronounced at week 78 (P = .001), representing a 14.5% increase from baseline. Similarly, telomerase activity showed progressive enhancement with vitamin D treatment, achieving significance by week 52 (P = .001) and continuing through week 78 (P < .0001), reflecting a 16.2% increase from baseline. Within-group analysis confirmed significant improvements over time in the vitamin D group (P = .002) but not in placebo (P = .18) group. After adjusting for potential confounders including body mass index, subscapular skinfold thickness, fasting blood glucose, and PTH, serum 25-hydroxyvitamin D levels maintained a significant independent association with both LTL (OR = 2.053; 95% CI, 1.410-2.243; P = .001) and telomerase activity (OR = 2.032; 95% CI, 1.410-2.254; P = .001) in the intervention group.

CONCLUSION: Vitamin D supplementation, over 78 weeks, is independently associated with increased LTL and telomerase activity in Asian Indian women with prediabetes.},
}

@article {pmid40854872,
year = {2025},
author = {Güzel, N and Schumacher, Y and Kricheldorf, K and Vieri, M and Kirschner, M and Gerhard-le Gars, AC and Panse, J and Tometten, M and Walter, J and Gehrig, A and Kunstmann, E and Holthöfer, L and Schweiger, S and Wolff, D and Kraft, F and Elbracht, M and Kurth, I and Brümmendorf, TH and Meyer, R and Beier, F},
title = {Allogeneic stem cell transplantation from variant-carrying family donors leads to long-term engraftment in Telomere Biology Disorders.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {142},
pmid = {40854872},
issn = {2044-5385},
}

@article {pmid40854256,
year = {2025},
author = {Musa, AA and Mamat-Hamidi, K and Idrus, Z and Chung, ELT and Samat, N and Kassim, NA},
title = {Effects of heat stress on growth metrics, carcass characteristics, telomere length, and gene expression in chickens.},
journal = {Poultry science},
volume = {104},
number = {11},
pages = {105698},
doi = {10.1016/j.psj.2025.105698},
pmid = {40854256},
issn = {1525-3171},
abstract = {This study investigated the impact of heat stress (HS) on growth performance, carcass traits, telomere length (TL), and gene expression profiles in three chicken breeds with varying growth rates: slow-growing (SAGA), medium-growing (Sasso), and fast-growing (Cobb 500). Three hundred 14-day-old male chicks were exposed to either control (25°C) or HS (34°C for 6 hours/day) conditions for four weeks in a controlled environment. Weekly growth metrics, TL at two and four weeks, Heat Shock Protein 70 (HSP70) and Insulin-Like Growth Factor-1 (IGF-1) expression in muscle and liver at two and four weeks of HS exposure, and carcass/organ yields at four weeks were analyzed. Cobb 500 chickens exhibited significant growth reductions under HS, while SAGA showed resilience. Notably, SAGA chickens exhibited a significant increase in intestinal organ mass under HS, which may indicate an adaptive response to thermal stress. HS exposure significantly shortened TL across all breeds, suggesting its utility as a universal biomarker for HS in chickens. All breeds upregulated HSP70 expression, with the Cobb 500 showing the most prominent increase. Similarly, IGF-1 was expressed (upregulated), particularly in 500 broilers at both time-points, highlighting breed-specific differences in growth performance. These results demonstrate breed-specific physiological adaptations to HS. TL and stress-related gene expression are crucial indicators of heat susceptibility and adaptation. The study provides insights into developing breed-specific management and breeding strategies to enhance poultry resilience to increasing global temperatures.},
}

@article {pmid40851308,
year = {2025},
author = {Huang, SB and Wu, J and Xu, ZJ and Mo, WT and Yuan, S and Jiang, XY and Wang, HF and Xie, L},
title = {TeloComp: an efficient toolkit for accurate assembly of the telomeres in T2T genome.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101492},
doi = {10.1016/j.xplc.2025.101492},
pmid = {40851308},
issn = {2590-3462},
}

@article {pmid40849907,
year = {2025},
author = {Janovič, T and Perez, GI and Boelting, G and Schmidt, JC},
title = {TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.},
journal = {Cell reports},
volume = {44},
number = {9},
pages = {116178},
doi = {10.1016/j.celrep.2025.116178},
pmid = {40849907},
issn = {2211-1247},
abstract = {The shelterin complex protects chromosome ends from aberrant DNA repair 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, but their stoichiometry and dynamics in cells remain poorly understood. To quantitatively analyze shelterin function, we generated a panel of human cancer cell lines expressing HaloTagged shelterin proteins from their endogenous loci. We determined both the total and telomeric abundance of each subunit, demonstrating that shelterin proteins are present at telomeres in equal numbers. Using single-molecule live-cell imaging, we showed that TRF1-TIN2-TPP1-POT1 and TRF2-RAP1 form distinct subcomplexes that bind non-overlapping sites on telomeric chromatin. TRF1-TIN2-TPP1-POT1 tightly associates with telomeres, whereas TRF2-RAP1 binds more dynamically, facilitating the recruitment of co-factors that protect chromosome ends. Altogether, our work provides mechanistic insight into shelterin function in telomere maintenance and advances our understanding of telomeric chromatin architecture.},
}

@article {pmid40849514,
year = {2025},
author = {Li, D and Li, W and Liao, X and Jiang, S and Ma, M and Hu, Z and Lin, K and Yu, W and Sun, X and Fan, Y and Wu, H and Yin, M and Wang, L and Suo, L and Long, H and Lu, X and Kuang, Y and Lyu, Q},
title = {NAD[+]-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1275},
pmid = {40849514},
issn = {2399-3642},
support = {23ZR1437500//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; 81901478//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Sirtuins/metabolism/genetics ; Animals ; *Blastocyst/metabolism ; *Telomere Shortening ; Mice ; Female ; *NAD/metabolism/deficiency ; Mice, Knockout ; Embryo Culture Techniques ; Telomere/metabolism ; },
abstract = {Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD[+]-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report that NAD[+] deficiency in in vitro-cultured blastocysts impairs Sirt6 function, triggering telomere shortening of the inner cell mass and possibly affecting newborns. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NAD[+] precursor) during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. mtROS accumulation and epigenetic modifications may also be involved in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.},
}

*Sirtuins/metabolism/genetics
Animals
*Blastocyst/metabolism
*Telomere Shortening
Mice
Female
*NAD/metabolism/deficiency
Mice, Knockout
Embryo Culture Techniques
Telomere/metabolism

@article {pmid40848782,
year = {2025},
author = {Shiburah, ME and de Oliveira, BCD and Bisetegn, H and de Oliveira, LS and Passos, AO and Silva, DA and Assis, LHC and Alves, CS and Ernst, E and Barreto, RM and Batista, MM and Soeiro, MNC and Menozzi, BD and Langoni, H and Aoki, JI and Coelho, AC and Miranda Junior, AS and Machado, CR and Cano, MIN},
title = {The absence of the Leishmania major telomerase TERT component links telomeres and cell homeostasis with infectivity.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {147036},
doi = {10.1016/j.ijbiomac.2025.147036},
pmid = {40848782},
issn = {1879-0003},
abstract = {We studied the impacts of deleting the telomerase reverse transcriptase component of the Leishmania major (LmTERT) telomerase complex. The Leishmania genus comprises species that cause leishmaniasis, a neglected disease that lacks effective treatment and control options, highlighting the need for alternative therapeutics. Telomerase plays a crucial role in maintaining the integrity of eukaryotic genomes by synthesizing telomeres through its TERT and telomerase RNA components. Here, we show that the absence of TERT in L. major has a pleiotropic effect on parasite homeostasis, causing growth and proliferation alterations, progressive telomere shortening, increased TERRA expression, and γH2A signaling, besides the early onset of autophagosomes and mitochondrial insults. The proteomic analysis of LmTERT knockout promastigotes compared with the parental lineage confirmed some of these alterations, showing an imbalance in constituents of chromatin, plasma membrane, mitochondria, and cytoskeleton, and the unexpected presence of proteins involved in autophagy and virulence at this parasite life stage. Inactivating LmTERT also impaired metacyclogenesis, abolishing the parasite's infectivity. These results establish a strong link between telomeres, cell homeostasis, and the parasite's infective capability, highlighting LmTERT as a promising target for antiparasitic strategies.},
}

@article {pmid40848099,
year = {2025},
author = {Adhikari, S and Yasmin, R and Bandyopadhyay, A and Nayek, K and Haldar, A and Ghosh, S and Mandal, P},
title = {Identification of molecular heterogeneity in telomere maintenance pathway of aplastic anemia.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {843},
pmid = {40848099},
issn = {1573-4978},
support = {BT/PR18640/BIC/101/924/2016 DATED 20.09.2017//DBT-BIOCARE/ ; BT/PR18640/BIC/101/924/2016 DATED 20.09.2017//DBT-BIOCARE/ ; NTA Ref. No.: 201610124607 Dated 01.04.2021//CSIR-UGC/ ; ECR/2017/000595, Dated:16.07.2018//DST-SERB/ ; },
}

@article {pmid40847086,
year = {2025},
author = {Feng, Z and Li, J and Zhang, H and Liu, S and Wang, Y and Zhou, M and Ding, Z and Xiao, L},
title = {Obesity impact on leukocyte telomere shortening and immune aging assessed by Mendelian randomization and transcriptomics analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30983},
pmid = {40847086},
issn = {2045-2322},
support = {82103785 and 82273582//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Obesity/genetics/immunology ; Mendelian Randomization Analysis ; *Telomere Shortening/genetics ; Male ; Female ; Body Mass Index ; Middle Aged ; *Transcriptome ; *Leukocytes/metabolism ; Polymorphism, Single Nucleotide ; Adult ; *Leukocytes, Mononuclear/metabolism ; Gene Expression Profiling ; Cellular Senescence/genetics ; *Aging/genetics/immunology ; Waist-Hip Ratio ; Telomere/genetics ; },
abstract = {Obesity and aging are key research topics in contemporary biomedical science. While studies have explored the effects of obesity on various health indicators, the precise mechanisms through which obesity may affect leukocyte telomere length (LTL)-and whether this impact contributes to accelerated immune cell senescence-remain unclear and warrant further investigation. In this study, we employed single nucleotide polymorphisms (SNPs) associated with four obesity indices-body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and waist-hip ratio (WHR)-as instrumental variables (IVs) to assess the causal relationship between these indices and LTL through Mendelian randomization (MR) analysis. Additionally, we analyzed transcriptome sequencing data from peripheral blood mononuclear cells (PBMCs) across three groups: lean individuals, individuals with obesity before undergoing bariatric surgery, and individuals with obesity after surgery, and focus on the expression changes of cellular senescence and telomere dynamics related genes in PBMCs of individuals with obesity before and after weight loss intervention. The results showed a negative causal relationship between BMI (B=-0.04, P < 0.0001), BFP (B=-0.06, P < 0.0001) and LTL without being impacted by lipid profiles and T2D. The negative causal relationship between WC (B=-0.04, P < 0.0001) and LTL may be dependent on lipid levels, but not on T2D. WHR had no significant causal relationship (P > 0.05). Transcriptomic analysis further revealed that individuals with obesity had higher expression of cellular senescence-related genes such as ID2, LMNA, and TENT4B in PBMCs compared to lean individuals, with expression levels of these genes significantly decreasing after bariatric surgery. These findings underscore the detrimental impact of obesity on telomere attrition and immune cell senescence, highlighting the potential benefits of obesity management for slowing the biological process of cellular and immune aging.},
}

Humans
*Obesity/genetics/immunology
Mendelian Randomization Analysis
*Telomere Shortening/genetics
Male
Female
Body Mass Index
Middle Aged
*Transcriptome
*Leukocytes/metabolism
Polymorphism, Single Nucleotide
Adult
*Leukocytes, Mononuclear/metabolism
Gene Expression Profiling
Cellular Senescence/genetics
*Aging/genetics/immunology
Waist-Hip Ratio
Telomere/genetics

@article {pmid40844718,
year = {2025},
author = {Oh, JH and Lee, HJ and Kim, W and Oh, DE and Kim, HK and Kim, EH and Choe, J and Jun, HR and Park, CW and Kang, YG and Kim, CJ and Sung, CO and Kim, TW},
title = {Whole genome sequencing reveals telomere associated genomic differences between healthy and unhealthy aging in a Korean population.},
journal = {Biogerontology},
volume = {26},
number = {5},
pages = {167},
pmid = {40844718},
issn = {1573-6768},
support = {2018IP0622 and 2019IF0590//Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea/ ; },
mesh = {Humans ; Middle Aged ; Aged ; Male ; *Telomere/genetics ; Female ; Whole Genome Sequencing ; *Aging/genetics ; Republic of Korea ; Case-Control Studies ; *Healthy Aging/genetics ; Genomic Instability ; Oxidative Stress/genetics ; DNA Repair/genetics ; Aged, 80 and over ; Telomere Homeostasis/genetics ; Telomere Shortening ; },
abstract = {One of the major challenges in modern biogerontology is understanding the accumulation of molecular damage and the manifestation of phenotypic heterogeneity during aging. Notably, genomic instability caused by impaired DNA damage repair along with telomere attrition are primary drivers of aging. However, how these aging-related characteristics differ in individuals who age healthily without developing major age-associated diseases remains unclear. Here, whole genome sequencing (WGS) was performed on 100 healthy agers (≥ 60 years old, no age-related diseases) and 100 unhealthy agers (≥ 60 years old, at least one age-related disease/condition) based on a case-control study. Telomere length was measured using TelSeq and Computel. High-functional impact germline variant (gHFI) burden and alteration pattern at the pathway level were also analyzed. The GTEx dataset including 751 individuals was used to observe the functional impact of identified germline variants at the molecular level. Telomere length showed minimal differences before 65 years of age but declined rapidly in unhealthy agers beyond this age. Additionally, healthy agers had lower gHFI burden, particularly in DNA repair genes such as BLM. Pathway analysis revealed enrichment of oxidative stress-related mutations in healthy agers, correlated with reduced oxidative stress and upregulated antioxidant enzymes (SOD1 and SOD2). Overall, genomic instability preserved through slow telomere attrition and reduced DNA repair defects plays a key role in healthy aging. Improved oxidative stress resistance may contribute to healthier aging, highlighting the role of genetic factors in reducing age-related decline and supporting overall well-being in later life.},
}

Humans
Middle Aged
Aged
Male
*Telomere/genetics
Female
Whole Genome Sequencing
*Aging/genetics
Republic of Korea
Case-Control Studies
*Healthy Aging/genetics
Genomic Instability
Oxidative Stress/genetics
DNA Repair/genetics
Aged, 80 and over
Telomere Homeostasis/genetics
Telomere Shortening

@article {pmid40841804,
year = {2025},
author = {Zhang, X and Chen, J and Zhou, W and Wen, J and Shi, Q},
title = {A telomere-to-telomere gap-free genome assembly of the protandrous hermaphrodite Asian seabass (Lates calcarifer).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1457},
pmid = {40841804},
issn = {2052-4463},
mesh = {Animals ; *Telomere ; *Bass/genetics ; *Genome ; Female ; Male ; *Hermaphroditic Organisms/genetics ; },
abstract = {As a protandrous hermaphroditic fish species with natural sex change from male to female, Asian seabass (Lates calcarifer) represents an attractive model for studying sequential hermaphroditism. In this study, we constructed the first telomere-to-telomere (T2T) gap-free genome assembly of Asian seabass, by integration of MGI short-read, PacBio HiFi long-read, ONT ultra-long and Hi-C sequencing technologies. The haplotypic 614.19 Mb genome sequences were successfully anchored onto 24 chromosomes, demonstrating exceptional contiguity with a contig N50 of 26.57 Mb. Comprehensive annotation revealed precise localization of telomeric repeats and centromeric regions across various chromosomes. Good results from Merqury (QV: 57.8), CRAQ (99.45%) and BUSCO (100%) indicate a high level of accuracy for the assembled genome. ONT ultra-long and PacBio HiFi sequencing data were aligned with the assembly using minimap2, resulting in a mapping rate over 98%. Repetitive elements accounted for 18.18% (111.64 Mb) of the entire genome, and a total of 25,093 protein-coding genes were annotated. This high-quality T2T genome assembly provides a valuable genetic resource for in-depth comparative genomics, population genetics, molecular breeding, and functional studies of this economically important marine species. This reference assembly also facilitates investigations into the detailed molecular mechanisms underlying its unique reproductive strategy of the protandrous hermaphrodite Asian seabass.},
}

Animals
*Telomere
*Bass/genetics
*Genome
Female
Male
*Hermaphroditic Organisms/genetics

@article {pmid40834628,
year = {2025},
author = {Rodríguez-Fernández, B and González-Escalante, A and Genius, P and E Evans, T and Ortiz-Romero, P and Minguillón, C and Kollmorgen, G and Ashton, NJ and Zetterberg, H and Blennow, K and Gispert, JD and Navarro, A and Suárez-Calvet, M and Sala-Vila, A and Crous-Bou, M and Vilor-Tejedor, N and , },
title = {Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.},
journal = {EBioMedicine},
volume = {119},
number = {},
pages = {105886},
doi = {10.1016/j.ebiom.2025.105886},
pmid = {40834628},
issn = {2352-3964},
abstract = {BACKGROUND: Short telomere length (TL), a hallmark of biological ageing, has been associated with an increased risk of Alzheimer's disease (AD), but its pathophysiological role remains unclear. This study explored the relationship between blood leukocyte TL (LTL), cerebrospinal fluid (CSF) AD biomarkers changes, and brain structure across early stages of the AD continuum.

METHODS: We included 346 cognitively unimpaired participants (aged 49-71) from the ALFA cohort, enriched for AD risk (53.2% APOE-ε4 carriers; 34% amyloid-positive). LTL was measured at baseline (visit 0) using quantitative PCR. Associations were assessed between baseline LTL and CSF biomarkers at visit 1 (mean follow-up from baseline = 3.98 years, SD = 1.02), and with changes in CSF biomarkers between visits 1 and 2 (mean interval = 3.45 years, SD = 0.58). Cortical thickness in ageing- and AD-vulnerable brain regions was evaluated by magnetic resonance imaging (MRI) at visit 1. Analyses were stratified by APOE-ε4 status and amyloid-tau (AT) profiles. Mediation models tested whether CSF biomarkers mediated LTL-cortical thickness associations.

FINDINGS: Shorter LTL was associated with higher astrocytic reactivity at visit 1 and with increased synaptic dysfunction over time. Among APOE-ε4 carriers and AT-positive individuals, shorter LTL was associated with higher p-tau181 and neurodegeneration markers. Shorter LTL was associated with greater cortical thickness in ageing- and AD-vulnerable regions, partially mediated by astrocytic reactivity biomarkers.

INTERPRETATION: These findings suggest that shorter telomeres are associated with early AD-related biological changes, potentially via mechanisms involving astrocytic reactivity and brain structural alterations. LTL may serve as an early marker of vulnerability to neurodegenerative processes in at-risk populations.

FUNDING: AARG-19-618265; PI19/00119; LCF/PR/GN17/10300004; TriBEKa-17-519007; # SLT002/16/00201.},
}

@article {pmid40831801,
year = {2025},
author = {Vakonaki, E and Vitiadou, MT and Paraskevopoulou, NI and Tzatzarakis, M and Baliou, S and Ioannou, P and Alegakis, A and Lamprakis, T and Fragkiadaki, P and Mylonaki, E and Volonaki, Z and Anagnostatou, N and Makrygiannakis, F and Makrigiannakis, A and Spandidos, DA and Tsatsakis, A and Hatzidaki, E},
title = {Correlation of telomere length between full and preterm neonates and their mothers.},
journal = {Experimental and therapeutic medicine},
volume = {30},
number = {4},
pages = {187},
pmid = {40831801},
issn = {1792-1015},
abstract = {Telomeres are nucleoprotein complexes that serve as protective caps from the DNA damage response at the ends of chromosomes. During aging, telomeres gradually shorten, and genomic instability arises through the induction of senescence. The present study aimed to elucidate the association between maternal characteristics, their medical history and pregnancy details with the telomere length (TL) of neonates. Blood samples were collected from 54 mothers and their neonates, and DNA extraction and measurement of TL was performed by quantitavive PCR. The results showed that maternal TL was negatively correlated with body mass index before pregnancy. A weak to moderate significant correlation was observed between maternal and neonatal TL. Non-significant differences were found between the maternal TL and their smoking habits, as well as medical and gestation history.},
}

@article {pmid40829179,
year = {2025},
author = {Monroe, TO},
title = {Genetic risk in telomere biology disorders: it adds up.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {16},
pages = {},
pmid = {40829179},
issn = {1558-8238},
mesh = {Humans ; *Telomere/genetics/pathology ; Genetic Predisposition to Disease ; *Telomere Homeostasis/genetics ; Genetic Variation ; Penetrance ; Risk Factors ; },
abstract = {For many conditions, genotyping aids in clinical decision making. However, interpreting the clinical significance of genetic variants remains challenging, in part because a single risk variant does not always lead to disease, and variant carriers experience variable outcomes. One hypothesis underlying these phenomena, which are known as incomplete penetrance and variable expressivity, respectively, is that additional common genetic variation beyond the primary variant influences the presence and severity of disease. In this issue of JCI, Poeschla et al. present a compelling argument that common variants linked to telomere length act together with high-risk telomere biology disorder variants to scale outcomes. These data support a model in which many variants interact to shape cumulative risk.},
}

Humans
*Telomere/genetics/pathology
Genetic Predisposition to Disease
*Telomere Homeostasis/genetics
Genetic Variation
Penetrance
Risk Factors

@article {pmid40826164,
year = {2025},
author = {Ismail, A and Jaalouk, K and Koteish, J and Tarhini, Y and Sadier, NS and Abou-Abbas, L},
title = {Correction: Exploring the association between depression and telomere length: A systematic review and meta-analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30230},
doi = {10.1038/s41598-025-15646-w},
pmid = {40826164},
issn = {2045-2322},
}

@article {pmid40826141,
year = {2025},
author = {Hill, C and Smyth, L and Kilner, J and Quinn, K and Scott, A and Neville, C and Kee, F and McGuinness, B and McKnight, AJ},
title = {Telomere length measures in the Northern Ireland cohort for the longitudinal study of ageing (NICOLA).},
journal = {BMC research notes},
volume = {18},
number = {1},
pages = {359},
pmid = {40826141},
issn = {1756-0500},
support = {PF2502\5//Vivensa Foundation/ ; R01AG068937/AG/NIA NIH HHS/United States ; R01AG068937/AG/NIA NIH HHS/United States ; R01AG068937/AG/NIA NIH HHS/United States ; STL/5569/19//HSC R&D division/ ; STL/5569/19//HSC R&D division/ ; STL/5569/19//HSC R&D division/ ; MRC MC_PC_20026//UKRI MRC/ ; MRC MC_PC_20026//UKRI MRC/ ; MRC MC_PC_20026//UKRI MRC/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; },
abstract = {OBJECTIVES: Using blood derived DNA collected from individuals within the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA), quantitative real-time polymerase chain reaction (RT-PCR) based absolute telomere length measures were derived in triplicate. This data is generated on a subset of participants (n = 2,971) within the NICOLA cohort at Wave 1 baseline. NICOLA commenced Wave 3 of data collection in Autumn 2024.

DATA DESCRIPTION: The NICOLA study recruited approximately 8,500 people from across Northern Ireland, with individuals recruited as representative of the Northern Ireland population. At recruitment, the NICOLA cohort was 45% male and 55% female. Adults were recruited over the age of 50, with approximately 50% of participants aged between 50 and 65, and 10% of participants over the age of 80. Telomere length (TL) values were determined for 2,971individuals (47.7% male) across 33 batches using the Absolute Human Telomere Length Quantification qPCR Assay kit and Roche LightCycler 480 II. Within-batch duplicate measures were established, as were water controls and non-template controls.},
}

@article {pmid40825835,
year = {2025},
author = {Chung, YP and Chung, WS},
title = {Telomere shortening in middle-aged and elderly individuals with varying severities of obstructive sleep apnea.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30277},
pmid = {40825835},
issn = {2045-2322},
abstract = {Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction during sleep and leads to oxidative stress, systemic inflammation, and potentially accelerated telomere shortening. Studies comparing telomere length (TL) in individuals with and without OSA have obtained inconsistent results. This study compared TL across individuals without and with OSA of varying severity. We recruited 103 participants from a sleep clinic, all of whom underwent in-laboratory polysomnography and TL measurement. To assess TL, quantitative PCR was conducted for genomic DNA extracted from peripheral blood samples. Four participants were excluded because of sleep durations of < 4 h during polysomnography. The final analysis included 99 individuals (46 men and 53 women). Among these individuals, 13 did not have OSA; 28, 24, and 34 had mild OSA, moderate OSA, and severe OSA, respectively. Telomeres were significantly longer in individuals without OSA than in individuals with mild, moderate, and severe OSA (8.4 ± 5.1 kb, 5.7 ± 3.1 kb, 5.7 ± 2.2 kb, and 4.8 ± 2.6 kb, respectively; P = 0.009). Among individuals aged < 50 years, no significant difference was observed in TL between the non-OSA and OSA groups. However, among individuals aged ≥ 50 years, individuals without OSA had significantly longer telomeres than did individuals with moderate to severe OSA. Our findings indicate that telomere shortening was significantly more pronounced in patients with increasing OSA severity than in individuals without OSA. Nocturnal hypoxia-induced inflammation in patients with OSA may contribute to telomere shortening.},
}

@article {pmid40825569,
year = {2025},
author = {Patel, HR and Alreja, K and Reis, ALM and Chang, JK and Chew, ZA and Jung, H and Hammond, JM and Deveson, IW and Ruiz-Herrera, A and Marin-Gual, L and Holleley, CE and Zhang, X and Lister, NC and Whiteley, S and Xiong, L and Dissanayake, DSB and Waters, PD and Georges, A},
title = {A near telomere-to-telomere phased genome assembly and annotation for the Australian central bearded dragon Pogona vitticeps.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40825569},
issn = {2047-217X},
support = {//Bioplatforms Australia/ ; DP220101429//Australian Research Council/ ; APP2021172//National Health and Medical Research Council/ ; PID2020-112557GB-I00//Spanish Ministry of Science and Innovation/ ; //AEI/ ; 2021SGR00122//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; //Catalan Institution for Research and Advanced Studies/ ; FPU18/03867//Spanish Ministry of Science, Innovation and University/ ; EST22/00661//Spanish Ministry of Science, Innovation and University/ ; },
abstract = {BACKGROUND: The central bearded dragon (Pogona vitticeps) is widely distributed in central eastern Australia and adapts readily to captivity. Among other attributes, it is distinctive because it undergoes sex reversal from ZZ genotypic males to phenotypic females at high incubation temperatures. Here, we report an annotated near telomere-to-telomere phased assembly of the genome of a female ZW central bearded dragon.

RESULTS: Genome assembly length is 1.75 Gbp with a scaffold N50 of 266.2 Mbp, N90 of 28.1 Mbp, 26 gaps, and 42.2% GC content. Most (99.6%) of the reference assembly is scaffolded into 6 macrochromosomes and 10 microchromosomes, including the Z and W microchromosomes, corresponding to the karyotype. The genome assembly exceeds standard recommended by the Earth Biogenome Project (6CQ40): 0.003% collapsed sequence, 0.03% false expansions, 99.8% k-mer completeness, 97.9% complete single-copy BUSCO genes, and an average of 93.5% of transcriptome data mappable back to the genome assembly. The mitochondrial genome (16,731 bp) and the model ribosomal DNA repeat unit (length 9.5 Kbp) were assembled. Male vertebrate sex genes Amh and Amhr2 were discovered as copies in the small non-recombining region of the Z chromosome, absent from the W chromosome. This, coupled with the prior discovery of differential Z and W transcriptional isoform composition arising from pseudo-autosomal sex gene Nr5a1, suggests that complex interactions between these genes, their autosomal copies, and their resultant transcription factors and intermediaries determine sex in the bearded dragon.

CONCLUSION: This high-quality assembly will serve as a resource to enable and accelerate research into the unusual reproductive attributes of this species and for comparative studies across the Agamidae and reptiles more generally.},
}

@article {pmid40825568,
year = {2025},
author = {Guang, X and Yang, J and Zhang, S and Guo, F and Li, L and Lian, X and Zeng, T and Cai, C and Liu, F and Li, Z and Hu, Y and Fang, D and He, W and Sahu, SK and Li, W and Lu, H and Li, Y and Liu, H and Xu, X and Gu, Y and Hu, F and Dong, Y and Wei, T},
title = {Telomere-to-telomere African wild rice (Oryza longistaminata) reference genome reveals segmental and structural variation.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf074},
pmid = {40825568},
issn = {2047-217X},
support = {32322063 to S.Z.//National Natural Science Foundation of China/ ; KQTD20221101093603011 to J.Y.//Shenzhen Science and Technology Program/ ; },
abstract = {Rice (Oryza sativa) is one of the most important staple food crops worldwide, and its wild relatives serve as an important gene pool in its breeding. Compared with cultivated rice species, African wild rice (Oryza longistaminata) has several advantageous traits, such as resistance to increased biomass production, clonal propagation via rhizomes, and biotic stresses. However, previous O. longistaminata genome assemblies have been hampered by gaps and incompleteness, restricting detailed investigations into their genomes. To streamline breeding endeavors and facilitate functional genomics studies, we generated a 331-Mb telomere-to-telomere (T2T) genome assembly for this species using a hybrid approach combining PacBio HiFi, Hi-C, and CycloneSEQ ultra-long reads, covering all telomeres and centromeres across the 12 chromosomes. This newly assembled genome has markedly improved over previous versions. Comparative analysis revealed a high degree of synteny with previously published genomes. A large number of structural variations were identified between O. longistaminata, O. glaberrima, and O. sativa. A total of 2,466 segmentally duplicated genes were enriched in cellular amino acid metabolic processes. We detected slight expansion of some subfamilies of resistance genes and transcription factors. This newly assembled T2T genome of O. longistaminata provides a valuable resource for the exploration and exploitation of beneficial alleles present in wild relative species of cultivated rice.},
}

@article {pmid40820358,
year = {2025},
author = {Gao, H and Ma, K and Cao, Z and Hu, X and Wang, Y and Lu, M and Zhao, X and Zhou, J and Liu, Y and Wang, M and Zhao, Z and Wang, Z and Li, J and Li, Y and Qin, Y and Bao, X and Jing, Y and Wang, F and Yu, Z},
title = {Absolute Length Distribution of Human Telomeres with Single-Molecule Techniques.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c11090},
pmid = {40820358},
issn = {1936-086X},
abstract = {Human telomeres exhibit progressive shortening with each replication cycle. This phenomenon plays a critical role in the onset of senescence and the development of cancers. The measurement of absolute telomere length (TL) is not only serving as a marker of aging, but also holds substantial medical relevance. However, current TL measurement technologies face significant challenges, including limited precision, inability to resolve TL heterogeneity or distinguish telomeric signals from interstitial telomeric sequences (ITS), and data inconsistency. Single-molecule mechanical techniques have shown promise in manipulating DNA and providing precise contour length measurements of DNA, making them suitable for assessing TL quantitatively. In this study, we developed a method, named single-molecule terminal restriction fragment (smTRF) analysis, for measuring telomeres at single-molecule resolution. We applied smTRF to seven human cancer cell lines and successfully determined TL ranging from a few to tens of kilobases, highlighting the versatility and high-fidelity performance of the smTRF assay. The smTRF data were validated against results from standard TRF, qPCR, and Q-FISH analysis, demonstrating well agreement and confirming the assay's reliability in the measurement of average TL. To further test the robustness of smTRF, we measured TL distribution profiles for 48 individuals, establishing the smTRF assay as a reliable tool for the accurate and precise measurement of human TLs. The comprehensive telomere profiles obtained via the smTRF assay promise to provide in-depth insights into public health research, particularly in the study of aging, where TL serves as a critical biomarker.},
}

@article {pmid40816244,
year = {2025},
author = {Sharma, B and Jamwal, RS and Chander, G and Sharma, M and Shah, R and Shankarayan, R and Bhan, S and Bhat, A and Bhat, AA and Kumar, R},
title = {Genetic insight into idiopathic male infertility in North India: Role of telomere maintenance genes.},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {313},
number = {},
pages = {114653},
doi = {10.1016/j.ejogrb.2025.114653},
pmid = {40816244},
issn = {1872-7654},
abstract = {BACKGROUND: Despite having a sizeable population and an increasing incidence of infertility, South Asia is still underrepresented in genetic studies of male reproductive health. In this area, little is known about idiopathic male infertility, which is frequently associated with subtle genetic variations. Both TERT (chromosome 5 [5p15.33]) and TERF2 (chromosome 16 [16q22.1]) genes are essential for spermatogenesis, as TERT is needed to maintain the telomere length, and TERF2 aids in chromosomal integrity and cell division. The purpose of this study is to fill a regional gap in molecular reproductive research by examining the relationship between telomere related genes TERT and TERF2, and idiopathic male infertility in the Jammu and Kashmir population of North India.

METHODS: In this study, 634 cytogenetically normal individuals were enrolled, out of which 220 were male infertile patients and 414 were fertile male controls. Individuals who had AZF microdeletions in their Y chromosome were excluded from the study. TaqMan assay was used to genotype two SNP's, TERT (rs10069690) and TERF2 (rs251796), and statistical analysis was carried out using various genetic models.

RESULTS: Under the dominant model, a significant association was observed between TERT SNP rs10069690 (T > C) (OR = 6.17;95 % CI:3.5-10.6; p < 0.05). A statistically significant connection was not seen between male infertility and TERF2 variant rs251796 (G > A) (p = 0.09) CONCLUSIONS: This is the first report from North India to link male infertility to TERT gene polymorphism, suggesting that telomere maintenance may play a part in impaired spermatogenesis. These results highlight the significance of region-specific molecular screening in a larger population with increased sample size and may aid in advancement of predictive diagnosis for male reproductive health, particularly in South Asian populations that are undeserved.},
}