@article {pmid39432594,
year = {2024},
author = {Dai, H and Chen, Z},
title = {Association between dietary vitamin K and telomere length: Based on NHANES 2001 to 2002.},
journal = {Medicine},
volume = {103},
number = {42},
pages = {e40157},
doi = {10.1097/MD.0000000000040157},
pmid = {39432594},
issn = {1536-5964},
mesh = {Humans ; Male ; Female ; *Nutrition Surveys ; Middle Aged ; *Telomere/drug effects ; *Vitamin K/administration & dosage ; *Diet/statistics & numerical data ; Adult ; Aged ; Cross-Sectional Studies ; Body Mass Index ; },
abstract = {As an anti-inflammatory and antioxidant, vitamin K has the potential to reduce telomere attrition. However, the correlation between dietary vitamin K and telomere length (TL) has not been reported. We aimed to investigate the association between these 2 variables. This study included 3754 participants from the National Health and Nutrition Examination Survey 2001-2002 database. We used multivariate linear regression and restricted cubic splines to assess the relationship between dietary vitamin K intake and TL. Subgroup analyses and interaction tests were utilized to examine the stability of the results. After adjusting for all variables, each unit increase in daily dietary intake of vitamin K lengthened telomeres by 0.22 base pairs (β = 0.22, 95% CI: 0.09-0.36, P = .001). Individuals with the highest dietary vitamin K intake had significantly longer TL (β = 80.27, 95% CI: 20.83-139.71, P = .008). Subgroup analyses suggested that this association persisted in populations stratified by gender, age, diabetes, cardiovascular disease (CVD), body mass index and total energy intake (P for interaction > .05). A linear relationship between dietary vitamin K intake and TL was observed in restricted cubic splines (P for nonlinear = .554). In conclusion, our findings suggest that dietary vitamin K intake is positively associated with TL, providing recent evidence to guide the management of healthy diets.},
}

Humans
Male
Female
*Nutrition Surveys
Middle Aged
*Telomere/drug effects
*Vitamin K/administration & dosage
*Diet/statistics & numerical data
Adult
Aged
Cross-Sectional Studies
Body Mass Index

@article {pmid39430825,
year = {2024},
author = {Ding, X and Zhang, Y and You, S},
title = {A novel prognostic model based on telomere-related lncRNAs in gastric cancer.},
journal = {Translational cancer research},
volume = {13},
number = {9},
pages = {4608-4624},
pmid = {39430825},
issn = {2219-6803},
abstract = {BACKGROUND: Telomeres are specialized structures at the ends of chromosomes that are important for their protection. Over time, long non-coding RNAs (lncRNAs) have gradually come into the spotlight as essential biomarkers of proliferation, migration, and invasion of human malignant tumors. Nevertheless, the impact of telomere-related lncRNAs (TRLs) in gastric cancer is currently unknown. In the present study, we screen the TRLs and identify a prognostic TRLs signature in gastric cancer.

METHODS: First, telomere-related genes (TRGs) were retrieved from the website, and RNA sequencing (RNA-seq) data and clinical data of stomach adenocarcinoma (STAD) patients were gathered from The Cancer Genome Atlas (TCGA) database. Gastric cancer patients' lncRNAs and overall survival (OS) were found to be related using univariate Cox regression analysis. Next, least absolute shrinkage and selection operator (LASSO) regression analysis and multifactorial Cox regression analysis were used to further screen telomere-related differentially expressed lncRNAs (TRDELs), and finally six lncRNAs were obtained, including LINC01537, CFAP61-AS1, DIRC1, RABGAP1L-IT1, DBH-AS1, and REPIN1-AS1. According to these six TRDELs, a prognostic model for gastric cancer was constructed. The samples were divided into the training group and the testing group at random, and the reliability of prognostic model was validated in both groups and overall samples. In addition, we performed Kaplan-Meier (K-M) survival curve analysis, independent prognostic analysis, and functional enrichment analysis to validate the predictive value and independence of the model, as well as immune cell correlation analysis, clustering analysis, and principal component analysis (PCA) to further explore the relationship between this model and the tumor cells. Finally, we performed the drug sensitivity analysis to identify a few small molecules that may have a therapeutic effect on gastric cancer.

RESULTS: Finally, we constructed a prognostic model for gastric cancer consisting of six TRDELs. According to the K-M curve, the prognosis of the low-risk group was noticeably superior than that of the high-risk group. Multivariate Cox regression analysis suggested that risk score was an independent prognostic element. Receiver operating characteristic (ROC) curves, nomogram, and calibration curve indicated that the prognostic model had good predictive ability. Functional enrichment analysis demonstrated major pathways with high- and low-risk groups. Next, both tumor microenvironment (TME) and immune correlation analysis showed discrepancy in the high- and low-risk groups. Through drug sensitivity analysis, we screened four small molecules that might be beneficial for gastric cancer treatment.

CONCLUSIONS: A prognostic model consisting of these six TRDELs was capable to predict the prognosis of gastric cancer patients.},
}

@article {pmid39430816,
year = {2024},
author = {Lin, H and Yin, W},
title = {Telomere-related prognostic signature for survival assessments in lung adenocarcinoma.},
journal = {Translational cancer research},
volume = {13},
number = {9},
pages = {4520-4533},
pmid = {39430816},
issn = {2219-6803},
abstract = {BACKGROUND: Telomere-related genes (TRGs) are important in many different types of cancers. However, there is a lack of research on the relationship between their expression and prognosis in lung adenocarcinoma (LUAD) patients. This study is to investigate the prognostic value of TRGs in LUAD and to develop a TRG signature that can predict patient survival.

METHODS: A total of 2,086 TRGs were obtained from a database of genes involved in telomere maintenance (TelNet), while the clinical information and tumor RNA expression profiles of 513 LUAD patients were acquired from The Cancer Genome Atlas (TCGA) database. Statistical methodologies, such as least absolute shrinkage and selection operator (LASSO)-Cox, were employed to construct a prognostic model with predictive capabilities.

RESULTS: We analyzed 1,339 telomere-associated differentially expressed genes and identified a ten-gene predictive signature for LUAD. This signature exhibited effective prognostic classification capabilities across multiple datasets, including GSE3141 (58 samples), GSE8894 (63 samples), GSE50081 (127 samples), and GSE72094 (398 samples). Furthermore, we screened tumor-sensitive drugs targeting this signature. High telomere levels were associated with reduced survival in lung cancer patients who underwent surgery. Compared to the traditional TNM (tumor node metastasis classification) grading method, our telomere-associated gene panel demonstrated superior prediction accuracy. Notably, patients in the high-risk group, defined by the telomere-associated signature, exhibited improved responses to immunotherapy, suggesting potential benefits for this subgroup of patients.

CONCLUSIONS: This study presents a comprehensive molecular signature comprising TRGs, which holds potential for functional and therapeutic investigations. Additionally, it serves as an integrated tool to identify crucial molecules for immunotherapy in lung cancer.},
}

@article {pmid39429092,
year = {2024},
author = {Rubio-Carrasco, K and de la Torre, PG and Martínez-Ezquerro, JD and Sánchez-García, S and García-Vences, E and Camacho-Arroyo, I and Rodríguez-Dorantes, M and González-Covarrubias, V},
title = {Hypertension Control Is Associated with Telomere Length in Older Adults.},
journal = {DNA and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1089/dna.2024.0173},
pmid = {39429092},
issn = {1557-7430},
abstract = {Hypertension is the leading risk for cardiovascular disease and worldwide mortality. Uncontrolled blood pressure worsens with age and its control is part of public health strategies especially for older adults. Telomere length (TL) has been associated with hypertension, with age and sex as relevant confounding factors, but it is not clear whether hypertension control in older adults impacts on TL and if this relationship is consistently age and sex dependent. TL was assessed in leukocytes of 369 hypertensive patients. Individuals were >60 years male (169) and female (200) and have been diagnosed and treated for hypertension for at least four years. TL was measured by RT-PCR using a commercial probe. Regression models were developed considering systolic and diastolic blood pressure control as dependent variables and age, sex, glucose, and lipid levels as confounding factors. TL showed a mean of 7.5 ± 5.1 Kb, and no difference between males and females was observed. We identified a significant association between systolic blood pressure control and TL (p value = 0.039) and a trend for diastolic blood pressure (p value = 0.061). These observations confirm and expand previous reports showing that hypertension control can have an impact on TL and consequently on other factors of healthy aging.},
}

@article {pmid39426946,
year = {2024},
author = {Wang, B and Kou, H and Wang, Y and Zhang, Q and Jiang, D and Wang, J and Zhao, Z and Zhou, Y and Zhang, M and Sui, L and Zhao, M and Liu, Y and Liu, Y and Shi, L and Wang, F},
title = {LAP2α orchestrates alternative lengthening of telomeres suppression through telomeric heterochromatin regulation with HDAC1: unveiling a potential therapeutic target.},
journal = {Cell death & disease},
volume = {15},
number = {10},
pages = {761},
pmid = {39426946},
issn = {2041-4889},
support = {32170762//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; Animals ; *Telomere Homeostasis/drug effects ; *Telomere/metabolism ; *Heterochromatin/metabolism ; Mice ; Cell Line, Tumor ; Osteosarcoma/genetics/pathology/metabolism/drug therapy ; Sister Chromatid Exchange ; DNA-Binding Proteins/metabolism/genetics ; Methotrexate/pharmacology/therapeutic use ; Cell Proliferation/drug effects ; Membrane Proteins ; },
abstract = {In response to the challenge of telomere attrition during DNA replication, cancer cells predominantly employ telomerase or, in 10-15% of cases, the alternative lengthening of telomeres (ALT). The intricate details of ALT, however, remain elusive. In this study, we unveil that the knockdown of lamina-associated polypeptide 2 alpha (LAP2α) in ALT cells results in telomere dysfunction, triggering a notable increase in ALT-associated hallmarks, including high frequencies of PML bodies (APBs), C-rich extrachromosomal circles (C-circles), and telomere sister chromatid exchange (T-SCE). Furthermore, LAP2α emerges as a crucial player in break-induced telomere replication for telomerase-positive cells following telomeric double-strand breaks. Mechanistically, our investigation suggests that LAP2α may influence the regulation of the heterochromatic state of telomeres, thereby affecting telomeric accessibility. In line with our findings, LAP2α expression is markedly reduced in ALT-positive osteosarcoma. And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion. This is evidenced by a significant inhibition of tumor proliferation in ALT-positive patient-derived xenograft (PDX) mouse models. These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.},
}

Humans
Animals
*Telomere Homeostasis/drug effects
*Telomere/metabolism
*Heterochromatin/metabolism
Mice
Cell Line, Tumor
Osteosarcoma/genetics/pathology/metabolism/drug therapy
Sister Chromatid Exchange
DNA-Binding Proteins/metabolism/genetics
Methotrexate/pharmacology/therapeutic use
Cell Proliferation/drug effects
Membrane Proteins

@article {pmid39426311,
year = {2024},
author = {Douglas, ME},
title = {How to write an ending: Telomere replication as a multistep process.},
journal = {DNA repair},
volume = {144},
number = {},
pages = {103774},
doi = {10.1016/j.dnarep.2024.103774},
pmid = {39426311},
issn = {1568-7856},
abstract = {Telomeres are protective nucleoprotein caps found at the natural ends of eukaryotic chromosomes and are crucial for the preservation of stable chromosomal structure. In cycling cells, telomeres are maintained by a multi-step process called telomere replication, which involves the eukaryotic replisome navigating a complex repetitive template tightly bound by specific proteins, before terminating at the chromosome end prior to a 5' resection step that generates a protective 3' overhang. In this review, we examine mechanistic aspects of the telomere replication process and consider how individual parts of this multistep event are integrated and coordinated with one-another.},
}

@article {pmid39422841,
year = {2024},
author = {Fu, H and Zhu, Y and Lin, L and Jiang, P and Cai, G and Zeng, L and Li, X and Zhang, Y and Li, C and Zhan, H and Zhang, B and Yang, Z},
title = {Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.},
journal = {Journal of cardiovascular translational research},
volume = {},
number = {},
pages = {},
pmid = {39422841},
issn = {1937-5395},
support = {82171578//National Natural Science Foundation of China/ ; 2023B03J0121//Science and Technology Project of Guangzhou City/ ; 20221800906192//Dongguan Science and Technology of Social Development Program/ ; },
abstract = {The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95% CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.},
}

@article {pmid39420560,
year = {2024},
author = {Lu, D and Liu, C and Ji, W and Xia, R and Li, S and Liu, Y and Liu, N and Liu, Y and Deng, XW and Li, B},
title = {Nanopore Ultra-long Sequencing and Adaptive Sampling Spur Plant Complete Telomere-to-Telomere Genome Assembly.},
journal = {Molecular plant},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molp.2024.10.008},
pmid = {39420560},
issn = {1752-9867},
abstract = {The pursuit of complete telomere-to-telomere (T2T) genome assembly in plants, challenged by genomic complexity, has been advanced by Oxford Nanopore Technologies (ONT), which offers ultra-long, real-time sequencing. Despite its promise, sequencing length and gap filling remain significant challenges. This study optimized DNA extraction and library preparation, achieving DNA lengths exceeding 485 Kb, average N50 read lengths of 80.57 Kb, with reaching up to 440 Kb, and maximum reads of 5.83 Mb. Importantly, it demonstrated that combining ultra-long sequencing and adaptive sampling can effectively fill gaps during assembly, evidenced by successfully achieving the Arabidopsis genome remaining gaps and an unknown telomeric region in watermelon. Our methodologies improve the feasibility of complete T2T genomic assemblies across plants, enhancing genome-based research in diverse fields.},
}

@article {pmid39420004,
year = {2024},
author = {Lam, SY and van der Lugt, R and Cerutti, A and Yalçin, Z and Thouin, AM and Simonetta, M and Jacobs, JJL},
title = {OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1[S824].},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8960},
pmid = {39420004},
issn = {2041-1723},
support = {812829//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions)/ ; 2019-2/12826//KWF Kankerbestrijding (Dutch Cancer Society)/ ; institutional grant to the Netherlands Cancer Institute//KWF Kankerbestrijding (Dutch Cancer Society)/ ; Institutional grant to the Netherlands Cancer Institute//Dutch Ministry of Health, Welfare and Sport | Rijksinstituut voor Volksgezondheid en Milieu (Netherlands National Institute for Public Health and the Environment)/ ; },
mesh = {Phosphorylation ; *Tripartite Motif-Containing Protein 28/metabolism/genetics ; *Ataxia Telangiectasia Mutated Proteins/metabolism/genetics ; *Telomere/metabolism ; Humans ; *DNA End-Joining Repair ; DNA Damage ; Ubiquitin-Protein Ligases/metabolism/genetics ; Heterochromatin/metabolism ; Endopeptidases/metabolism/genetics ; HEK293 Cells ; Ubiquitination ; },
abstract = {Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres. Hence, we performed a functional genetic screen to search for ubiquitin system factors that promote KAP1[S824] phosphorylation, a robust DDR marker at deprotected telomeres. We identified that the OTU family deubiquitinase (DUB) OTUD5 promotes KAP1[S824] phosphorylation by facilitating ATM activation, through stabilization of the ubiquitin ligase UBR5 that is required for DNA damage-induced ATM activity. Loss of OTUD5 impairs KAP1[S824] phosphorylation, which suppresses end-joining mediated DNA repair at deprotected telomeres and at DNA breaks in heterochromatin. Moreover, we identified an unexpected role for the heterochromatin factor KAP1 in suppressing DNA repair at telomeres. Altogether our work reveals an important role for OTUD5 and KAP1 in relaying DDR-dependent kinase signaling to the control of DNA repair at telomeres and heterochromatin.},
}

Phosphorylation
*Tripartite Motif-Containing Protein 28/metabolism/genetics
*Ataxia Telangiectasia Mutated Proteins/metabolism/genetics
*Telomere/metabolism
Humans
*DNA End-Joining Repair
DNA Damage
Ubiquitin-Protein Ligases/metabolism/genetics
Heterochromatin/metabolism
Endopeptidases/metabolism/genetics
HEK293 Cells
Ubiquitination

@article {pmid39416992,
year = {2024},
author = {Cadiñanos, J and Rodríguez-Centeno, J and Montejano, R and Esteban-Cantos, A and Mena-Garay, B and Jiménez-González, M and Saiz-Medrano, G and de Miguel, R and Rodríguez-Artalejo, F and Bernardino, JI and Marcelo-Calvo, C and Gutierrez-García, L and Martínez-Martín, P and Díez Vidal, A and de Gea Grela, A and Ortolá, R and Rodés, B and Arribas, JR},
title = {Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1.},
journal = {Open forum infectious diseases},
volume = {11},
number = {10},
pages = {ofae550},
pmid = {39416992},
issn = {2328-8957},
abstract = {BACKGROUND: People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown.

METHODS: This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S).

RESULTS: A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95-1.17] vs 1.28 [IQR, 1.12-1.48]; P < .001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77-0.98], P < .001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, -0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, -0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI, .87-.94]; P < .001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02-1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population.

CONCLUSIONS: PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general population.},
}

@article {pmid39413125,
year = {2024},
author = {Zhang, Y and Ma, Z and Kang, L and Yang, L},
title = {Effect of telomere shortening on disease progression in patients with inflammatory bowel disease: A systematic review and meta-analysis protocol.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0311662},
doi = {10.1371/journal.pone.0311662},
pmid = {39413125},
issn = {1932-6203},
mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/pathology ; *Systematic Reviews as Topic ; *Disease Progression ; *Telomere Shortening ; *Meta-Analysis as Topic ; Telomere/genetics ; },
abstract = {INTRODUCTION: Inflammatory bowel disease (IBD) remains a major public health challenge worldwide. In recent years, it has been discovered that a link between telomere shortening and disease progression in IBD patients has been present. However, there is controversy as to whether telomere shortening precipitates disease progression or disease progression causes telomere shortening. There is also a shortage of systematic reviews and data synthesis to explain the association between telomere shortening and disease progression in individuals with IBD. We aimed to systematically review the association between telomere shortening and disease advancement in individuals with IBD to inform future studies.

METHODS AND ANALYSIS: We will undertake a thorough search of the electronic database from the beginning until December 31, 2023. We will search the databases: MEDLINE/PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Database (Wanfang), CMB, Cochrane Library, Cochran Clinical Trials Registry, and the World Health Organization International Clinical Trials Registry Platform. Two reviewers will assess the discovered citations for eligibility based on the title and abstract before proceeding to the full-text and data extraction phases. These reviewers will debate and settle any conflicts that arise during the inclusion process; a third reviewer will settle any issues that remain. The validated data extraction form will be used to collect data for eligible research. The included studies will undergo a quality and bias check and will proceed meta-analysis.

DISCUSSION: This systematic review and meta-analysis will reveal a positive correlation between illness progression and telomere shortening in individuals with IBD, perhaps demonstrating three causal links between them. This study will conduct the first systematic review and meta-analysis examining the correlation between telomere shortening and illness advancement in individuals with IBD. Exploring the connection between these two situations can enhance the comprehension of the development and advancement of IBD.

PROSPERO registration number: CRD42024501171.},
}

Humans
*Inflammatory Bowel Diseases/genetics/pathology
*Systematic Reviews as Topic
*Disease Progression
*Telomere Shortening
*Meta-Analysis as Topic
Telomere/genetics

@article {pmid39410901,
year = {2024},
author = {Polo, CM and Pereira de Brito, TR and Roberto Silva, W and Lima, DB and Nunes, DP and Colombo, FA and Orlandi, AADS and Corona, LP},
title = {Shorter Telomere Length is Associated with Food Insecurity in Older People: A Cross-Sectional Study.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098320942240924074044},
pmid = {39410901},
issn = {1874-6128},
abstract = {BACKGROUND: Telomere length has been investigated as a biomarker of biological aging and is associated with several diseases, lifestyle, and socioeconomic factors.

OBJECTIVE: This study aimed to verify whether food insecurity is associated with shorter telomere length in older people.

METHODS: This is a cross-sectional study carried out in a municipality in the interior of Brazil, with a sample of 440 older people from the community. For telomere length analysis, a blood sample was obtained from each participant, followed by real-time qPCR, and sociodemographic and health information was collected through interviews. Food security/insecurity was measured using the reduced version of the Brazilian Food Insecurity Scale. Descriptive analysis and multiple logistic regression were performed to analyze the factors associated with shorter telomere length, adopting a significance level of 5%.

RESULTS: We found that food insecurity was significantly associated with shorter telomere length, regardless of age group, skin color, tabagism, physical activity, milk and dairy consumption, living arrangement, and basic activities of daily life.

CONCLUSION: The findings show the importance of ensuring full access to adequate nutrition for the older population, who are physiologically and socially vulnerable.},
}

@article {pmid39409990,
year = {2024},
author = {Loukopoulou, C and Nikolouzakis, T and Koliarakis, I and Vakonaki, E and Tsiaoussis, J},
title = {Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer.},
journal = {Cancers},
volume = {16},
number = {19},
pages = {},
doi = {10.3390/cancers16193370},
pmid = {39409990},
issn = {2072-6694},
abstract = {Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.},
}

@article {pmid39408829,
year = {2024},
author = {Rubtsova, MP and Nikishin, DA and Vyssokikh, MY and Koriagina, MS and Vasiliev, AV and Dontsova, OA},
title = {Telomere Reprogramming and Cellular Metabolism: Is There a Link?.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
doi = {10.3390/ijms251910500},
pmid = {39408829},
issn = {1422-0067},
support = {23-SH04-20//Development Program of the MSU Interdisciplinary Scientific and Educational School "Molecular technologies of living systems and synthetic biology" at the Lomonosov Moscow State University/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; Animals ; *Telomere Homeostasis ; Cell Proliferation ; Cellular Reprogramming/genetics ; Germ Cells/metabolism ; },
abstract = {Telomeres-special DNA-protein structures at the ends of linear eukaryotic chromosomes-define the proliferation potential of cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with the increased proliferative potential of specific cell types, such as stem and germ cells. This elongation can be permanent in these cells and is activated temporally during immune response activation and regeneration processes. The activation of telomere lengthening mechanisms is coupled with increased proliferation and the cells' need for energy and building resources. To obtain the necessary nutrients, cells are capable of finely regulating energy production and consumption, switching between catabolic and anabolic processes. In this review, we focused on the interconnection between metabolism programs and telomere lengthening mechanisms during programmed activation of proliferation, such as in germ cell maturation, early embryonic development, neoplastic lesion growth, and immune response activation. It is generally accepted that telomere disturbance influences biological processes and promotes dysfunctionality. Here, we propose that metabolic conditions within proliferating cells should be involved in regulating telomere lengthening mechanisms, and telomere length may serve as a marker of defects in cellular functionality. We propose that it is possible to reprogram metabolism in order to regulate the telomere length and proliferative activity of cells, which may be important for the development of approaches to regeneration, immune response modulation, and cancer therapy. However, further investigations in this area are necessary to improve the understanding and manipulation of the molecular mechanisms involved in the regulation of proliferation, metabolism, and aging.},
}

Humans
*Telomere/metabolism/genetics
Animals
*Telomere Homeostasis
Cell Proliferation
Cellular Reprogramming/genetics
Germ Cells/metabolism

@article {pmid39408588,
year = {2024},
author = {Kim, M and Kang, D and Kim, HS and Lee, JM and Park, S and Kwag, D and Lee, C and Hong, Y and Na, D and Koh, Y and Sun, CH and An, H and Kim, YJ and Kim, Y},
title = {Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
doi = {10.3390/ijms251910258},
pmid = {39408588},
issn = {1422-0067},
support = {NRF-2022R1A2C2006746//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; Male ; Middle Aged ; Female ; *Clonal Hematopoiesis/genetics ; Adult ; *Hematopoietic Stem Cells/metabolism ; *Telomere/genetics ; Aged ; Transplantation, Homologous ; Mutation ; Myelodysplastic Syndromes/genetics/therapy/etiology ; Bone Marrow/metabolism ; },
abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
Male
Middle Aged
Female
*Clonal Hematopoiesis/genetics
Adult
*Hematopoietic Stem Cells/metabolism
*Telomere/genetics
Aged
Transplantation, Homologous
Mutation
Myelodysplastic Syndromes/genetics/therapy/etiology
Bone Marrow/metabolism

@article {pmid39406502,
year = {2024},
author = {Kamath, SS and Bindra, M and Pal, D and Jain, C},
title = {Telomere-to-telomere assembly by preserving contained reads.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.279311.124},
pmid = {39406502},
issn = {1549-5469},
abstract = {Automated telomere-to-telomere (T2T) de novo assembly of diploid and polyploid genomes remains a formidable task. A string graph is a commonly used assembly graph representation in the assembly algorithms. The string graph formulation employs graph simplification heuristics, which drastically reduce the count of vertices and edges. One of these heuristics involves removing the reads contained in longer reads. In practice, this heuristic occasionally introduces gaps in the assembly by removing all reads that cover one or more genome intervals. The factors contributing to such gaps remain poorly understood. In this work, we mathematically derived the frequency of observing a gap near a germline and a somatic heterozygous variant locus. Our analysis shows that (i) an assembly gap due to contained read deletion is an order of magnitude more frequent in Oxford Nanopore reads than PacBio HiFi reads due to differences in their read-length distributions, and (ii) this frequency decreases with an increase in the sequencing depth. Drawing cues from these observations, we addressed the weakness of the string graph formulation by developing the RAFT assembly algorithm. RAFT addresses the issue of contained reads by fragmenting reads and producing a more uniform read-length distribution. The algorithm retains spanned repeats in the reads during the fragmentation. We empirically demonstrate that RAFT significantly reduces the number of gaps using simulated datasets. Using real Oxford Nanopore and PacBio HiFi datasets of the HG002 human genome, we achieved a twofold increase in the contig NG50 and the number of haplotype-resolved T2T contigs compared to Hifiasm.},
}

@article {pmid39401753,
year = {2023},
author = {Baser, E and Inandiklioglu, N and Aydogan Kırmızı, D and Ercan, F and Caniklioğlu, A and Kara, M and Onat, T and Yalvac, ES},
title = {Correction: Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {227},
number = {2},
pages = {e267},
doi = {10.1055/a-2416-9430},
pmid = {39401753},
issn = {1439-1651},
}

@article {pmid39400911,
year = {2024},
author = {Machelová, A and Dadejová, MN and Franek, M and Mougeot, G and Simon, L and Le Goff, S and Duc, C and Bassler, J and Demko, M and Schwarzerová, J and Desset, S and Probst, AV and Dvořáčková, M},
title = {The histone chaperones ASF1 and HIRA are required for telomere length and 45S rDNA copy number homeostasis.},
journal = {The Plant journal : for cell and molecular biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/tpj.17041},
pmid = {39400911},
issn = {1365-313X},
support = {23-06643S//Grantová Agentura České Republiky/ ; MUNI/R/1364/2023//Grant Agency of Masaryk University/ ; ANR-11 JSV2 009 01//French National Research Agency/ ; ANR-12 ISV6 0001//French National Research Agency/ ; CZ.02.01.01/00/22_008/0004581//European Regional Development Fund Programme Johannes Amos Comenius/ ; },
abstract = {Genome stability is significantly influenced by the precise coordination of chromatin complexes that facilitate the loading and eviction of histones from chromatin during replication, transcription, and DNA repair processes. In this study, we investigate the role of the Arabidopsis H3 histone chaperones ANTI-SILENCING FUNCTION 1 (ASF1) and HISTONE REGULATOR A (HIRA) in the maintenance of telomeres and 45S rDNA loci, genomic sites that are particularly susceptible to changes in the chromatin structure. We find that both ASF1 and HIRA are essential for telomere length regulation, as telomeres are significantly shorter in asf1a1b and hira mutants. However, these shorter telomeres remain localized around the nucleolus and exhibit a comparable relative H3 occupancy to the wild type. In addition to regulating telomere length, ASF1 and HIRA contribute to silencing 45S rRNA genes and affect their copy number. Besides, ASF1 supports global heterochromatin maintenance. Our findings also indicate that ASF1 transiently binds to the TELOMERE REPEAT BINDING 1 protein and the N terminus of telomerase in vivo, suggesting a physical link between the ASF1 histone chaperone and the telomere maintenance machinery.},
}

@article {pmid39399813,
year = {2024},
author = {Yerukala Sathipati, S and Jeong, S and Sharma, P and Mayer, J and Sharma, R and Ho, SY and Hebbring, S},
title = {Exploring prognostic implications of miRNA signatures and telomere maintenance genes in kidney cancer.},
journal = {Molecular therapy. Oncology},
volume = {32},
number = {4},
pages = {200874},
pmid = {39399813},
issn = {2950-3299},
abstract = {Kidney cancer, particularly clear cell renal cell carcinoma (KIRC), presents significant challenges in disease-specific survival. This study investigates the prognostic potential of microRNAs (miRNAs) in kidney cancers, including KIRC and kidney papillary cell carcinoma (KIRP), focusing on their interplay with telomere maintenance genes. Utilizing data from The Cancer Genome Atlas, miRNA expression profiles of 166 KIRC and 168 KIRP patients were analyzed. An evolutionary learning-based kidney survival estimator identified robust miRNA signatures predictive of 5-year survival for both cancer types. For KIRC, a 37-miRNA signature showed a correlation coefficient (R) of 0.82 and mean absolute error (MAE) of 0.65 years. Similarly, for KIRP, a 23-miRNA signature exhibited an R of 0.82 and MAE of 0.64 years, demonstrating comparable predictive accuracy. These signatures also displayed diagnostic potential with receiver operating characteristic curve values between 0.70 and 0.94. Bioinformatics analysis revealed targeting of key telomere-associated genes such as TERT, DKC1, CTC1, and RTEL1 by these miRNAs, implicating crucial pathways such as cellular senescence and proteoglycans in cancer. This study highlights the significant link between miRNAs and telomere genes in kidney cancer survival, offering insights for therapeutic targets and improved prognostic markers.},
}

@article {pmid39388510,
year = {2024},
author = {Song, X and Lin, D and Wang, D and Weng, S and Qiu, S and Zhou, W and Xiao, A and Zhang, N},
title = {Association of lymphocyte count and serum albumin concentration with telomere length in Chinese sanitation workers.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0311736},
doi = {10.1371/journal.pone.0311736},
pmid = {39388510},
issn = {1932-6203},
mesh = {Humans ; Male ; Lymphocyte Count ; Adult ; China ; Female ; Case-Control Studies ; Middle Aged ; *Sanitation ; *Serum Albumin/analysis ; Telomere/metabolism ; Lymphocytes/metabolism ; Inflammation/blood ; Telomere Homeostasis ; East Asian People ; },
abstract = {OBJECTIVE: This study aimed to examine the association between inflammation-related indicators (IRIs) and telomere length (TL) in Chinese sanitation workers.

METHODS: This study adopted a case-control design, conducted from January to December 2022 in Shenzhen, a city in eastern China. A total of 80 sanitation workers, as well as 80 matched controls, were randomly recruited from the Luohu district of Shenzhen city in China. Their blood samples were collected and analyzed for the IRIs and TL in the Medical Laboratory of Shenzhen Prevention and Treatment Center for Occupational Diseases. The relationship between IRIs and TL was analyzed using multivariate linear regression, and their dose-response relationship was explored using restricted cubic spline analysis.

RESULTS: The systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in the sanitation workers in comparison to the controls. Moreover, the lymphocyte count (LYM), serum albumin concentration (ALB), and TL were found to be lower in the sanitation workers compared to the controls (P < 0.05). After adjusting for potential confounding variables, LYM was negatively correlated with TL in the sanitation workers (β = -0.31, 95% CI: -0.57, -0.05), whereas no correlation was observed in the controls. Furthermore, ALB demonstrated a non-linear relationship with TL in sanitation workers.

CONCLUSION: We found higher novel inflammatory markers (SII, PLR, and NLR) in the sanitation workers, and identified a correlation between LYM and ALB with shortened TL in them, providing new evidence for the effect of elevated inflammation on accelerated aging in Chinese sanitation workers.},
}

Humans
Male
Lymphocyte Count
Adult
China
Female
Case-Control Studies
Middle Aged
*Sanitation
*Serum Albumin/analysis
Telomere/metabolism
Lymphocytes/metabolism
Inflammation/blood
Telomere Homeostasis
East Asian People

@article {pmid39385582,
year = {2024},
author = {Fernández de la Puente, M and Marti, A and Canudas, S and Zalba, G and Razquin, C and Boccardi, V and Mecocci, P and Babio, N and Castañer-Niño, O and Toledo, E and Buil-Cosiales, P and Salas-Salvadó, J and García-Calzón, S},
title = {Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.},
journal = {Age and ageing},
volume = {53},
number = {10},
pages = {},
doi = {10.1093/ageing/afae216},
pmid = {39385582},
issn = {1468-2834},
support = {021/CB07/03/2004//CIBEROBN/ ; //Instituto de Salud Carlos III/ ; //Fondo de Investigación para la Salud/ ; PI13/00462//European Regional Development Fund/ ; //Institución Catalana de Investigación y Estudios Avanzados/ ; IJC2019-040796-I//Juan de la Cierva-Incorporación/ ; 2020-PMF-PIPF-8//Rovira i Virgili University and Diputació de Tarragona/ ; },
mesh = {Humans ; Male ; Aged ; Female ; *Cognition ; *Cardiovascular Diseases/epidemiology/prevention & control ; *Cognitive Dysfunction/epidemiology/diagnosis/psychology/prevention & control ; Middle Aged ; Spain/epidemiology ; Time Factors ; Telomere ; Cognitive Aging/psychology ; Age Factors ; Risk Factors ; Telomere Homeostasis ; Diet, Mediterranean ; Risk Assessment ; Executive Function ; Aging/psychology ; Heart Disease Risk Factors ; Telomere Shortening ; },
abstract = {BACKGROUND: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment.

METHODS: We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models.

RESULTS: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (β: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (β: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (β: 0.33; 95%CI: 0.12 to 0.52; P = 0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years.

CONCLUSIONS: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.},
}

Humans
Male
Aged
Female
*Cognition
*Cardiovascular Diseases/epidemiology/prevention & control
*Cognitive Dysfunction/epidemiology/diagnosis/psychology/prevention & control
Middle Aged
Spain/epidemiology
Time Factors
Telomere
Cognitive Aging/psychology
Age Factors
Risk Factors
Telomere Homeostasis
Diet, Mediterranean
Risk Assessment
Executive Function
Aging/psychology
Heart Disease Risk Factors
Telomere Shortening

@article {pmid39379870,
year = {2024},
author = {Vrettou, M and Lager, S and Toffoletto, S and Iliadis, SI and Kallak, TK and Agnafors, S and Nieratschker, V and Skalkidou, A and Comasco, E},
title = {Peripartum depression symptom trajectories, telomere length and genotype, and adverse childhood experiences.},
journal = {BMC psychiatry},
volume = {24},
number = {1},
pages = {661},
pmid = {39379870},
issn = {1471-244X},
abstract = {BACKGROUND: As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery.

METHODS: Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped.

RESULTS: TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls.

CONCLUSIONS: The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.},
}

@article {pmid39379607,
year = {2024},
author = {Barchitta, M and Maugeri, A and La Mastra, C and Favara, G and La Rosa, MC and Magnano San Lio, R and Gholizade Atani, Y and Gallo, G and Agodi, A},
title = {Pre-pregnancy BMI, gestational weight gain, and telomere length in amniotic fluid: a causal graph analysis.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {23396},
pmid = {39379607},
issn = {2045-2322},
support = {"La coorte Mamma and Bambino: un approccio Multisettoriale Alla salute Materno-Infantile Mediante valutazione dell'Esposoma nelle Donne, MAMI-MED"//University of Catania, Italy, Department of Medical and Surgical Science and Advanced Technologies "GF Ingrassia" Programma ricerca di ateneo UNICT 2020-22 linea 2, PIAno di inCEntivi per la RIcerca di Ateneo 2020/2022/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Body Mass Index ; *Amniotic Fluid/metabolism ; *Gestational Weight Gain ; Adult ; Telomere/genetics ; Telomere Homeostasis ; Overweight/genetics ; Infant, Newborn ; },
abstract = {Previous investigations have suggested a potential association between pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with telomere length (TL) in various tissues of pregnant women and newborns. Nonetheless, as association does not imply causation, our objective was to investigate the causal connections among pre-pregnancy BMI, GWG, and TL in amniotic fluid. The analysis included 136 mother-child pairs from the Mamma & Bambino cohort, and three causal graph models were developed to depict the interconnections between pre-pregnancy BMI, GWG, and TL. Causal graph analysis was conducted utilizing the do-operator to estimate the causal effect of GWG and the controlled direct effect of pregestational BMI. We revealed that transitioning from non-adequate to adequate GWG had a positive impact on the probability of having "long" TL (i.e., a value greater than the population median) in all three models. When considering the effect of pre-pregnancy BMI, the highest probability of "long" TL was observed in normal weight women with adequate GWG. In contrast, the effect of adequate GWG became minimal among overweight women. These results shed light on the potential causality between pre-pregnancy BMI, GWG, and TL in amniotic fluid, emphasizing the importance of appropriate weight management before and during pregnancy for optimal TL outcomes.},
}

Humans
Female
Pregnancy
*Body Mass Index
*Amniotic Fluid/metabolism
*Gestational Weight Gain
Adult
Telomere/genetics
Telomere Homeostasis
Overweight/genetics
Infant, Newborn

@article {pmid39377032,
year = {2024},
author = {Assari, S and Dezfuli, M and Peyrovinasab, A and Zare, H},
title = {Does Adulthood Socioeconomic Status Predict Subsequent Telomere Length in Racially and Ethnically Diverse Women?.},
journal = {Journal of biomedical and life sciences},
volume = {4},
number = {1},
pages = {47-59},
pmid = {39377032},
issn = {2771-2303},
abstract = {BACKGROUND: Telomere length is a critical biomarker of cellular aging and overall health. While childhood socioeconomic status (SES) indicators such as education and poverty can have long-lasting effects on biological aging, research has shown contradictory results regarding the impact of adulthood SES on future telomere length, particularly in racially and ethnically diverse individuals. This study investigates the effects of baseline adulthood SES indicators such as education and poverty on telomere length nine years later in women, using data from the Future of Families and Child Wellbeing Study (FFCWS).

METHODS: We analyzed data from the FFCWS, a longitudinal cohort study. The sample included baseline adulthood SES and follow-up telomere length measure of women (n = 2,421) with varying socioeconomic conditions. Telomere length was measured from saliva samples nine years after the baseline measure of adulthood SES. Education, poverty, and marital status at baseline were assessed. Multivariate linear regression models were used to examine the association between adulthood SES indicators at baseline and future telomere length, controlling for potential confounders.

RESULTS: From the total 2,421 women, 675 were Latino White, 1,158 were non-Latino Black, and 588 were non-Latino White. Our findings indicate that for non-Latino White women poverty at certain level, and childbirth weight, and for non-Latino Black maternal age were predictors of telomere lengths nine years later.

CONCLUSION: Poverty at a specific level, maternal age and childbirth weight serve as predictors of telomere lengths nine years later in some women. These findings underscore the importance of socioeconomic factors and early-life influences in understanding telomere dynamics and aging processes among women from varied racial and ethnic backgrounds.},
}

@article {pmid39373625,
year = {2024},
author = {Jiang, G and Cao, L and Wang, Y and Li, L and Wang, Z and Zhao, H and Qiu, Y and Feng, B},
title = {Causality between telomere length and the risk of hematologic malignancies: A bidirectional Mendelian randomization study.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0402},
pmid = {39373625},
issn = {2767-9764},
abstract = {Growing evidence indicates a relationship between telomere length (TL) and the stage, prognosis, and treatment responsiveness of hematopoietic malignancies. However, the relationship between TL and the risk of hematologic malignancies remains unclear, considering the vulnerability of observational studies to potential confounding and reverse causation. Two-sample bidirectional mendelian randomization (MR) analysis was conducted utilizing publicly available genome-wide association study data to assess whether TL was causally associated with the risk of hematologic malignancies. The inverse variance-weighted approach was used as the primary assessment approach to evaluate the effects of the causes, augmented by the weighted median and MR-Egger methods. Cochran's Q test, MR Egger intercept test, MR-PRESSO, and leave-one-out analysis were performed to evaluate sensitivity, heterogeneity, and pleiotropy. According to forward MR estimations, longer TL was related to an increased risk of acute lymphocytic leukemia (OR=2.690, p=0.041), chronic lymphocytic leukemia (OR=2.155, p=0.005), multiple myeloma (OR=1.845, p=0.024), Hodgkin lymphoma (OR=1.697, p=0.014), and non-Hodgkin lymphoma (OR=1.737, p=0.009). Specific types of non-Hodgkin lymphoma were also associated with TL. The reverse MR results revealed that hematological malignancies had no effect on TL. This MR analysis revealed an association between longer TL and an increased risk of specific hematologic malignancies, indicating a potential role of TL in the risk evaluation and management in hematologic malignancies.},
}

@article {pmid39371255,
year = {2024},
author = {Rolles, B and Tometten, M and Meyer, R and Kirschner, M and Beier, F and Brümmendorf, TH},
title = {Inherited Telomere Biology Disorders: Pathophysiology, Clinical Presentation, Diagnostics, and Treatment.},
journal = {Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie},
volume = {51},
number = {5},
pages = {292-309},
pmid = {39371255},
issn = {1660-3796},
abstract = {BACKGROUND: Telomeres are the end-capping structures of all eukaryotic chromosomes thereby protecting the genome from damage and degradation. During the aging process, telomeres shorten continuously with each cell division until critically short telomeres prevent further proliferation whereby cells undergo terminal differentiation, senescence, or apoptosis. Premature aging due to critically short telomere length (TL) can also result from pathogenic germline variants in the telomerase complex or related genes that typically counteract replicative telomere shortening in germline and certain somatic cell populations, e.g., hematopoetic stem cells. Inherited diseases that result in altered telomere maintenance are summarized under the term telomere biology disorder (TBD).

SUMMARY: Since TL both reflects but more importantly restricts the replicative capacity of various human tissues, a sufficient telomere reserve is particularly important in cells with high proliferative activity (e.g., hematopoiesis, immune cells, intestinal cells, liver, lung, and skin). Consequently, altered telomere maintenance as observed in TBDs typically results in premature replicative cellular exhaustion in the respective organ systems eventually leading to life-threatening complications such as bone marrow failure (BMF), pulmonary fibrosis, and liver cirrhosis.

KEY MESSAGES: The recognition of a potential congenital origin in approximately 10% of adult patients with clinical BMF is of utmost importance for the proper diagnosis, appropriate patient and family counseling, to prevent the use of inefficient treatment and to avoid therapy-related toxicities including appropriate donor selection when patients have to undergo stem cell transplantation from related donors. This review summarizes the current state of knowledge about TBDs with particular focus on the clinical manifestation patterns in children (termed early onset TBD) compared to adults (late-onset TBD) including typical treatment- and disease course-related complications as well as their prognosis and adequate therapy. Thereby, it aims to raise awareness for a disease group that is currently still highly underdiagnosed particularly when it first manifests itself in adulthood.},
}

@article {pmid39370492,
year = {2024},
author = {Farias, TG and Santos, MSD and Mencalha, AL and da Fonseca, AS},
title = {Low-power red laser and blue LED modulate telomere maintenance and length in human breast cancer cells.},
journal = {Lasers in medical science},
volume = {39},
number = {1},
pages = {248},
pmid = {39370492},
issn = {1435-604X},
support = {88887.636295/2021-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; E26/019.001958/2019//Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; },
mesh = {Humans ; *Breast Neoplasms/radiotherapy/genetics/pathology ; Female ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomere/radiation effects ; *Low-Level Light Therapy/methods ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; Cell Line, Tumor ; RNA, Messenger/metabolism/genetics ; MCF-7 Cells ; Telomere Homeostasis/radiation effects ; Shelterin Complex ; Telomere-Binding Proteins ; },
abstract = {Cancer cells have the ability to undergo an unlimited number of cell divisions, which gives them immortality. Thus, the cancer cell can extend the length of its telomeres, allowing these cells to divide unlimitedly and avoid entering the state of senescence or cellular apoptosis. One of the main effects of photobiomodulation (PBM) is the increase in the production of adenosine triphosphate (ATP) and free radicals, mainly reactive oxygen species (ROS). Existent data indicates that high levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on cancer cell telomere maintenance is needed. This work aimed to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the TRF1 and TRF2 mRNA levels and telomere length in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm[-2], 0.77 W/cm[-2]) and blue LED (482 J cm[-2], 5.35 W/cm[-2]), alone or in combination, and the relative mRNA levels of the genes and telomere length were assessed by quantitative reverse transcription polymerase chain reaction. The results suggested that exposure to certain red laser and blue LED fluences decreased the TRF1 and TRF2 mRNA levels in both human breast cancer cells. Telomere length was increased in MCF-7 cells after exposure to red laser and blue LED. However, telomere length in MDA-MB-231 was shortened after exposure to red laser and blue LED at fluences evaluated. Our research suggests that photobiomodulation induced by red laser and low-power blue LED could alter telomere maintenance and length.},
}

Humans
*Breast Neoplasms/radiotherapy/genetics/pathology
Female
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Telomere/radiation effects
*Low-Level Light Therapy/methods
*Telomeric Repeat Binding Protein 1/metabolism/genetics
Cell Line, Tumor
RNA, Messenger/metabolism/genetics
MCF-7 Cells
Telomere Homeostasis/radiation effects
Shelterin Complex
Telomere-Binding Proteins

@article {pmid39368029,
year = {2024},
author = {Xing, B and Yu, J and Liu, Y and He, S and Gao, Q and Chen, X and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {The negative association between sodium-driven nutrient pattern and telomere length: the chain mediating role of diastolic pressure and waist circumference.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {201},
pmid = {39368029},
issn = {1720-8319},
support = {2022YFC2010102//National Key R&D Program of China/ ; CIFMS,2021-I2M-1-002//the CAMS Innovation Fund for Medical Sciences/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Waist Circumference ; Cross-Sectional Studies ; *Blood Pressure/physiology ; *Telomere ; Adult ; China ; Sodium, Dietary ; Diet ; Aged ; Leukocytes/metabolism/physiology ; Telomere Homeostasis/physiology ; },
abstract = {BACKGROUND: Numerous single nutrients have been suggested to be linked with leukocyte telomere length (LTL). However, data on nutrient patterns (NPs), particularly in Chinese population, are scarce. This study aimed to examine the relationship between nutrient-based dietary patterns and LTL, and the potential role of metabolic factors.

METHODS: Dietary data was obtained via 24-hour food recalls, and principal component analysis (PCA) was used to identify NPs. LTL was assessed using a real-time PCR assay. Multiple linear regression was conducted to determine the association between NPs and LTL. The potential role of metabolism among them was analyzed using mediation models.

RESULTS: A total of 779 individuals from northern China were included in this cross-sectional analysis. Five main nutrient patterns were identified. Adjusted linear regression showed that the "high sodium" pattern was inversely associated with LTL (B=-0.481(-0.549, -0.413), P < 0.05). The "high vitamin E-fat" pattern exhibited a positive correlation (B = 0.099(0.029, 0.170), P < 0.05), whereas the "high vitamin A-vitamin B2" pattern was negatively correlated with LTL (B=-0.120(-0.183, -0.057), P < 0.05), respectively. No significant associations were observed for the remaining nutrient patterns. The mediation model demonstrated that diastolic blood pressure and waist circumference could individually and collectively mediate the negative impact of the "high sodium" pattern on LTL (BDBP=-0.0173(-0.0333, -0.0041), BWC=-0.0075(-0.0186, -0.0004), Bjoint=-0.0033 (-0.0072, -0.0006), all P < 0.05). Moreover, glycosylated hemoglobin and non-high-density lipoprotein cholesterol mediate the relationship between the "high vitamin E-fat" pattern and LTL (BHbA1c=0.0170(0.0010,0.0347), Bnon-HDL-C= 0.0335 (0.0067, 0.0626), all P < 0.05), respectively.

CONCLUSIONS: The "high sodium" and "high vitamin E-fat" nutrient patterns demonstrated negative and positive associations with LTL and metabolic indicators may play complex mediating roles in these relationships.},
}

Humans
Male
Female
Middle Aged
*Waist Circumference
Cross-Sectional Studies
*Blood Pressure/physiology
*Telomere
Adult
China
Sodium, Dietary
Diet
Aged
Leukocytes/metabolism/physiology
Telomere Homeostasis/physiology

@article {pmid39367328,
year = {2024},
author = {Félix, NQ and Tornquist, L and Sehn, AP and D'avila, HF and Todendi, PF and de Moura Valim, AR and Reuter, CP},
title = {The association of telomere length with body mass index and immunological factors differs according to physical activity practice among children and adolescents.},
journal = {BMC pediatrics},
volume = {24},
number = {1},
pages = {633},
pmid = {39367328},
issn = {1471-2431},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , Brasil/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , Brasil/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , Brasil/ ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Body Mass Index ; Child ; Adolescent ; *Exercise ; *Sleep ; *Telomere ; Brazil ; Screen Time ; Leisure Activities ; Immunologic Factors ; Linear Models ; },
abstract = {BACKGROUND: This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents.

METHODS: A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren's leisure-time physical activity practices.

RESULTS: An inverse association between BMI and telomere length (β: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (β: 0.151; 95% CI: 0.029; 0.278) and neutrophils (β: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA.

CONCLUSION: The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity.},
}

Humans
Male
Female
Cross-Sectional Studies
*Body Mass Index
Child
Adolescent
*Exercise
*Sleep
*Telomere
Brazil
Screen Time
Leisure Activities
Immunologic Factors
Linear Models

@article {pmid39353511,
year = {2024},
author = {Wu, Y and Huang, C and Fan, B and Wu, H and Mei, Y and Cheng, F},
title = {The relationship between leukocyte telomere length and risk of depression and anxiety: Evidence from UK Biobank.},
journal = {Journal of affective disorders},
volume = {369},
number = {},
pages = {195-201},
doi = {10.1016/j.jad.2024.09.138},
pmid = {39353511},
issn = {1573-2517},
abstract = {BACKGROUND: Telomere length is a cellular aging marker implicated in various health outcomes. A growing body of evidence suggests a link between leukocyte telomere length (LTL) and mental health outcomes. However, there have been no studies focused on the relationship between LTL and the future risk of depression and anxiety. This study aimed to investigate the associations between LTL and depression/anxiety, examining both cross-sectional prevalence and prospective incidence.

METHODS: Data from 364,331 UK Biobank participants were analyzed. LTL was measured at baseline, and mental health status was assessed through hospital records and online surveys. Logistic regression and Cox proportional hazards models were employed for cross-sectional and prospective analyses with appropriate adjustment, respectively.

RESULTS: The mean (SD) age of the subjects was 57.03 (13.34) years and follow-up duration was 8.80 (5.39) years. Cross-sectionally, shorter LTL was associated with increased odds of depression (OR: 1.401, 95 % CI: 1.291-1.521) and anxiety (1.347 (1.198-1.515)) at baseline, which remained significant after adjustment. Among those free of depression/anxiety at baseline, baseline shorter LTL was associated with a higher risk of incident depression (HR: 1.615, 95 % CI: 1.447-1.803) and anxiety (1.430 (1.293-1.581)) during follow-up period. These associations remained robust after adjusting for various covariates.

CONCLUSIONS: Our findings indicated an association between shorter telomeres and an increased risk of prevalent depression/anxiety and shorter telomeres precede the onset of these mental health conditions. Considering the potential clinical implications, our study underscores the relevance of LTL as a predictive tool for identifying individuals at risk of developing depression and anxiety.},
}

@article {pmid39356569,
year = {2024},
author = {Premužić, V and Toupance, S and Hollander, A and Stipančić, Ž and Bukal, N and Jelaković, A and Brzić, I and Čulig, B and Slade, N and Benetos, A and Jelaković, B},
title = {Longer Telomere Length in Balkan Endemic Nephropathy Patients Undergoing Chronic Hemodialysis is Associated with Lower Cardiovascular Mortality.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000000603},
pmid = {39356569},
issn = {2641-7650},
abstract = {BACKGROUND: Balkan endemic nephropathy (BEN) is characterized with later onset and milder forms of hypertension, and with lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). Longer telomeres are associated with better cardiovascular (CV) prognosis. Therefore, we hypothesized that telomere length (TL) could be longer in BEN patients compared to other ESKD patients.

METHODS: A total of 124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN) were enrolled and followed-up for 72 months. TL was measured in leukocytes by Southern blot at inclusion.

RESULTS: Age and sex-adjusted TL was significantly longer in the BEN group (p<0.001). TL was negatively associated with carotid-femoral PWV in BEN patients. BEN patients had significantly lower CV mortality than non-BEN ESKD patients (p<0.001). In the BEN group shorter TL (1kb change) was the only determinant of shorter survival (HR 0.11). Using the TL threshold defined by ROC analysis (TL < 6.21 kb), we showed in both groups significantly higher CV mortality in the presence of short telomeres (Log-rank (Mantel-p<0.001).

CONCLUSIONS: Longer telomeres are associated with less CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with arterial stiffness and positively associated with survival. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.},
}

@article {pmid39355591,
year = {2024},
author = {Sun, JY and Xu, Q and Shen, H and Huang, W and Qu, Q and Sun, W and Kong, XQ},
title = {The Association between Leucocyte Telomere Length and Survival Outcomes in Patients with Cardiovascular Disease.},
journal = {Reviews in cardiovascular medicine},
volume = {25},
number = {9},
pages = {333},
pmid = {39355591},
issn = {2153-8174},
abstract = {BACKGROUND: We explore the association between leucocyte telomere length (LTL) and all-cause and cardiovascular disease (CVD)-specific death in CVD patients.

METHODS: We acquired 1599 CVD patients from a nationally representative US population survey for this study. We applied Kaplan-Meier curves, adjusted weighted Cox regression models, and restricted cubic spline to investigate the association between LTL and all-cause death. Additionally, we employed competing risk regression to assess the impact of LTL on cardiovascular-specific death, setting non-cardiovascular death as a competing event.

RESULTS: The overall mortality rate was 31.0% after a median follow-up of 13.9 years. Patients with shorter LTL exhibited a higher risk of all-cause death, with an adjusted hazard ratio (HR) of 1.25 (95% confidence interval (CI): 1.05-1.48). Restricted cubic spline illustrated a linear dose-response relationship. In gender-specific analyses, female patients with shorter LTL showed a higher risk of death (weighted HR, 1.79; 95% CI, 1.29-2.48), whereas this association was not observed in males (weighted HR, 0.90; 95% CI, 0.61-1.32). The Fine-Gray competing risk model revealed no significant relationship between LTL and cardiovascular-specific mortality but a significant association with non-cardiovascular death (adjusted HR, 1.24; 95% CI, 1.02-1.51).

CONCLUSIONS: LTL is inversely associated with all-cause death in female CVD patients. The significant correlation between reduced LTL and increased all-cause mortality emphasizes LTL as a potential marker for tertiary prevention against cardiovascular disease.},
}

@article {pmid39355254,
year = {2024},
author = {Xu, W and Sang, S and Wang, J and Guo, S and Zhang, X and Zhou, H and Chen, Y},
title = {Identification of telomere-related lncRNAs and immunological analysis in ovarian cancer.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1452946},
pmid = {39355254},
issn = {1664-3224},
mesh = {Humans ; *RNA, Long Noncoding/genetics ; Female ; *Ovarian Neoplasms/genetics/immunology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; *Telomere/genetics ; Cell Line, Tumor ; Nomograms ; Middle Aged ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; },
abstract = {BACKGROUND: Ovarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined.

METHODS: Relevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells.

RESULTS: A six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells.

CONCLUSION: Our study identified potential biomarkers for the six-TRLs model related to the prognosis of OC.},
}

Humans
*RNA, Long Noncoding/genetics
Female
*Ovarian Neoplasms/genetics/immunology/mortality
Prognosis
*Biomarkers, Tumor/genetics
*Gene Expression Regulation, Neoplastic
*Telomere/genetics
Cell Line, Tumor
Nomograms
Middle Aged
Lymphocytes, Tumor-Infiltrating/immunology/metabolism

@article {pmid39354183,
year = {2024},
author = {Wilsnack, C and Rising, CJ and Pearce, EE and Forbes Shepherd, R and Thompson, AS and Majid, A and Werner-Lin, A and Savage, SA and Hutson, SP},
title = {Defining the complex needs of families with rare diseases-the example of telomere biology disorders.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39354183},
issn = {1476-5438},
abstract = {Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases.},
}

@article {pmid39351882,
year = {2024},
author = {Lee, H and Niida, H and Sung, S and Lee, J},
title = {Haplotype-resolved de novo assembly revealed unique characteristics of alternative lengthening of telomeres in mouse embryonic stem cells.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae842},
pmid = {39351882},
issn = {1362-4962},
support = {NRF-2020R1A2C3003352//National Research Foundation of Korea/ ; SSTF-BA1501-52//Samsung Science and Technology Foundation/ ; },
abstract = {Telomeres protect chromosome ends from DNA damage responses, and their dysfunction triggers genomic alterations like chromosome fusion and rearrangement, which can lead to cellular death. Certain cells, including specific cancer cells, adopt alternative lengthening of telomere (ALT) to counteract dysfunctional telomeres and proliferate indefinitely. While telomere instability and ALT activity are likely major sources of genomic alteration, the patterns and consequences of such changes at the nucleotide level in ALT cells remain unexplored. Here we generated haplotype-resolved genome assemblies for type I ALT mouse embryonic stem cells, facilitated by highly accurate or ultra-long reads and Hi-C reads. High-quality genome revealed ALT-specific complex chromosome end structures and various genomic alterations including over 1000 structural variants (SVs). The unique sequence (mTALT) used as a template for type I ALT telomeres showed traces of being recruited into the genome, with mTALT being replicated with remarkably high accuracy. Subtelomeric regions exhibited distinct characteristics: resistance to the accumulation of SVs and small variants. We genotyped SVs at allele resolution, identifying genes (Rgs6, Dpf3 and Tacc2) crucial for maintaining ALT telomere stability. Our genome assembly-based approach elucidated the unique characteristics of ALT genome, offering insights into the genome evolution of cells surviving telomere-derived crisis.},
}

@article {pmid39350941,
year = {2024},
author = {Lin, F and Luo, J and Zhu, Y and Liang, H and Li, D and Han, D and Chang, Q and Pan, P and Zhang, Y},
title = {Association Between Adverse Early Life Factors and Telomere Length in Middle and Late Life.},
journal = {Innovation in aging},
volume = {8},
number = {9},
pages = {igae070},
pmid = {39350941},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: Telomere length (TL) has been acknowledged as biomarker of biological aging. Numerous investigations have examined associations between individual early life factors and leukocyte TL; however, the findings were far from consistent.

RESEARCH DESIGN AND METHODS: We evaluated the relationship between individual and combined early life factors and leukocytes TL in middle and late life using data from the UK Biobank. The early life factors (eg, maternal smoking, breastfeeding, birth weight, and comparative body size and height to peers at age 10) were measured. The regression coefficients (β) and 95% confidence interval (CI) were applied to assess the link of the early life factors and TL in adulthood. Flexible parametric survival models incorporated age to calculate the relationship between early life factors and life expectancy.

RESULTS: Exposure to maternal smoking, lack of breastfeeding, low birth weight, and shorter height compared to peers at age 10 were identified to be associated with shorter TL in middle and older age according to the large population-based study with 197 504 participants. Individuals who experienced more than 3 adverse early life factors had the shortest TL in middle and late life (β = -0.053; 95% CI = -0.069 to -0.038; p < .0001), as well as an average of 0.54 years of life loss at the age of 45 and 0.49 years of life loss at the age of 60, compared to those who were not exposed to any early life risk factors.

DISCUSSION AND IMPLICATIONS: Early life factors including maternal smoking, non-breastfed, low birth weight, and shorter height compared to peers at age 10 were associated with shorter TL in later life. In addition, an increased number of the aforementioned factors was associated with a greater likelihood of shorter TL in adulthood, as well as a reduced life expectancy.},
}

@article {pmid39350032,
year = {2024},
author = {Ferguson, S and Bar-Ness, YD and Borevitz, J and Jones, A},
title = {A telomere-to-telomere Eucalyptus regnans genome: unveiling haplotype variance in structure and genes within one of the world's tallest trees.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {913},
pmid = {39350032},
issn = {1471-2164},
abstract = {BACKGROUND: Eucalyptus regnans (Mountain Ash) is an Australian native giant tree species which form forests that are among the highest known carbon-dense biomasses in the world. To enhance genomic studies in this ecologically important species, we assembled a high-quality, mostly telomere-to-telomere complete, chromosome-level, haplotype-resolved reference genome. We sampled a single tree, the Centurion, which is currently a contender for the world's tallest flowering plant.

RESULTS: Using long-read sequencing data (PacBio HiFi, Oxford Nanopore ultra-long reads) and chromosome conformation capture data (Hi-C), we assembled the most contiguous and complete Eucalyptus reference genome to date. For each haplotype, we observed contig N50s exceeding 36 Mbp, scaffold N50s exceeding 43 Mbp, and genome BUSCO completeness exceeding 99%. The assembled genome revealed extensive structural variations between the two haplotypes, consisting mostly of insertions, deletions, duplications and translocations. Analysis of gene content revealed haplotype-specific genes, which were enriched in functional categories related to transcription, energy production and conservation. Additionally, many genes reside within structurally rearranged regions, particularly duplications, suggesting that haplotype-specific variation may contribute to environmental adaptation in the species.

CONCLUSIONS: Our study provides a foundation for future research into E. regnans environmental adaptation, and the high-quality genome will be a powerful resource for conservation of carbon-dense giant tree forests.},
}

@article {pmid39349834,
year = {2024},
author = {Saraswati, S and Martínez, P and Serrano, R and Mejías, D and Graña-Castro, O and Álvarez Díaz, R and Blasco, MA},
title = {Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39349834},
issn = {2092-6413},
abstract = {Tubulointerstitial fibrosis associated with chronic kidney disease (CKD) represents a global health care problem. We previously reported that short and dysfunctional telomeres lead to interstitial renal fibrosis; however, the cell-of-origin of kidney fibrosis associated with telomere dysfunction is currently unknown. We induced telomere dysfunction by deleting the Trf1 gene encoding a telomere-binding factor specifically in renal fibroblasts in both short-term and long-term life-long experiments in mice to identify the role of fibroblasts in renal fibrosis. Short-term Trf1 deletion in renal fibroblasts was not sufficient to trigger kidney fibrosis but was sufficient to induce inflammatory responses, ECM deposition, cell cycle arrest, fibrogenesis, and vascular rarefaction. However, long-term persistent deletion of Trf1 in fibroblasts resulted in kidney fibrosis accompanied by an elevated urinary albumin-to-creatinine ratio (uACR) and a decrease in mouse survival. These cellular responses lead to the macrophage-to-myofibroblast transition (MMT), endothelial-to-mesenchymal transition (EndMT), and partial epithelial-to-mesenchymal transition (EMT), ultimately causing kidney fibrosis at the humane endpoint (HEP) when the deletion of Trf1 in fibroblasts is maintained throughout the lifespan of mice. Our findings contribute to a better understanding of the role of dysfunctional telomeres in the onset of the profibrotic alterations that lead to kidney fibrosis.},
}

@article {pmid39349547,
year = {2024},
author = {Geng, D and Liu, H and Wang, H and Wang, H},
title = {Telomere length exhibits inverse association with migraine among Americans aged 20-50 years, without implications beyond age 50: a cross-sectional study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {22597},
pmid = {39349547},
issn = {2045-2322},
support = {H2020307041//the Natural Science Foundation of Hebei Province/ ; 236Z7745G//the Central Government Guides Local Funds for Science and Technology Development/ ; },
mesh = {Humans ; *Migraine Disorders/genetics ; Middle Aged ; Adult ; Cross-Sectional Studies ; Male ; Female ; Young Adult ; *Telomere/genetics ; United States/epidemiology ; Nutrition Surveys ; Telomere Shortening ; Age Factors ; Telomere Homeostasis ; Aged ; Leukocytes/metabolism ; },
abstract = {Migraine, common in individuals under 50 years, is linked to oxidative stress. The association between telomere length shortening and migraine, along with potential age-related influences, has not been comprehensively studied. This cross-sectional study included data from 6169 participants in the National Health and Nutrition Survey (NHANES) from 1999 to 2002, encompassing information on peripheral blood leukocyte telomere length, severe headache or migraine, and potential confounders. Stratifying by age (20-50 years, > 50 years), we employed multivariable logistic regression, restricted cubic splines and interaction test to investigate age-influenced telomere length in relation to migraine. In participants aged 20-50 years, the odds ratio (OR) for migraine in the shortest telomere length group T1 (0.39-0.89) was 1.35 (95% confidence interval [95% CI] 1.01, 1.79) compared to the longest group T3 (1.10-9.42), whereas in those aged > 50 years, the OR of T1 was 0.93 (95% CI 0.60, 1.43). Additionally, telomere length and age interacted in the development of migraine (p for interaction: 0.010). In individuals aged 20-50, an L-shaped relationship was found between telomere length and migraine, with an inflection point at 1.02T/S ratio. The OR was 9.34 (95% CI 1.56, 55.99) for telomere lengths < 1.02T/S ratio. These findings suggest age influences the association between telomere length and migraine in U.S. adults.},
}

Humans
*Migraine Disorders/genetics
Middle Aged
Adult
Cross-Sectional Studies
Male
Female
Young Adult
*Telomere/genetics
United States/epidemiology
Nutrition Surveys
Telomere Shortening
Age Factors
Telomere Homeostasis
Aged
Leukocytes/metabolism

@article {pmid39348051,
year = {2025},
author = {Nonaka, K and Aida, J and Hasegawa, Y and Arai, T and Ishiwata, T and Takubo, K},
title = {Telomere Length Measurement in Human Tissue Sections by Quantitative Fluorescence In Situ Hybridization (Q-FISH).},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2857},
number = {},
pages = {9-14},
pmid = {39348051},
issn = {1940-6029},
mesh = {Humans ; *In Situ Hybridization, Fluorescence/methods ; *Telomere/genetics/metabolism ; *Peptide Nucleic Acids/metabolism/genetics ; *Paraffin Embedding/methods ; Tissue Fixation/methods ; Telomere Homeostasis ; Centromere/metabolism/genetics ; },
abstract = {Telomeres in most somatic cells shorten with each cell division, and critically short telomeres lead to cellular dysfunction, cell cycle arrest, and senescence. Thus, telomere shortening is an important hallmark of human cellular senescence. Quantitative fluorescence in situ hybridization (Q-FISH) using formalin-fixed paraffin-embedded (FFPE) tissue sections allows the estimation of telomere lengths in individual cells in histological sections. In our Q-FISH method, fluorescently labelled peptide nucleic acid (PNA) probes are hybridized to telomeric and centromeric sequences in FFPE human tissue sections, and relative telomere lengths (telomere signal intensities relative to centromere signal intensities) are measured. This chapter describes our Q-FISH protocols for assessing relative telomere lengths in FFPE human tissue sections.},
}

Humans
*In Situ Hybridization, Fluorescence/methods
*Telomere/genetics/metabolism
*Peptide Nucleic Acids/metabolism/genetics
*Paraffin Embedding/methods
Tissue Fixation/methods
Telomere Homeostasis
Centromere/metabolism/genetics

@article {pmid39346776,
year = {2024},
author = {Fu, C and Tian, X and Wu, S and Chu, X and Cheng, Y and Wu, X and Yang, W},
title = {Role of telomere dysfunction and immune infiltration in idiopathic pulmonary fibrosis: new insights from bioinformatics analysis.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1447296},
pmid = {39346776},
issn = {1664-8021},
abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by unexplained irreversible pulmonary fibrosis. Although the etiology of IPF is unclear, studies have shown that it is related to telomere length shortening. However, the prognostic value of telomere-related genes in IPF has not been investigated.

METHODS: We utilized the GSE10667 and GSE110147 datasets as the training set, employing differential expression analysis and weighted gene co-expression network analysis (WGCNA) to screen for disease candidate genes. Then, we used consensus clustering analysis to identify different telomere patterns. Next, we used summary data-based mendelian randomization (SMR) analysis to screen core genes. We further evaluated the relationship between core genes and overall survival and lung function in IPF patients. Finally, we performed immune infiltration analysis to reveal the changes in the immune microenvironment of IPF.

RESULTS: Through differential expression analysis and WGCNA, we identified 35 significant telomere regulatory factors. Consensus clustering analysis revealed two distinct telomere patterns, consisting of cluster A (n = 26) and cluster B (n = 19). Immune infiltration analysis revealed that cluster B had a more active immune microenvironment, suggesting its potential association with IPF. Using GTEx eQTL data, our SMR analysis identified two genes with potential causal associations with IPF, including GPA33 (PSMR = 0.0013; PHEIDI = 0.0741) and MICA (PSMR = 0.0112; PHEIDI = 0.9712). We further revealed that the expression of core genes is associated with survival time and lung function in IPF patients. Finally, immune infiltration analysis revealed that NK cells were downregulated and plasma cells and memory B cells were upregulated in IPF. Further correlation analysis showed that GPA33 expression was positively correlated with NK cells and negatively correlated with plasma cells and memory B cells.

CONCLUSION: Our study provides a new perspective for the role of telomere dysfunction and immune infiltration in IPF and identifies potential therapeutic targets. Further research may reveal how core genes affect cell function and disease progression, providing new insights into the complex mechanisms of IPF.},
}

@article {pmid39344239,
year = {2024},
author = {Li, J and Liu, PP and Wang, Y and Ren, CY and Zhang, M},
title = {Lectin YKL-40 Level and Telomere Length are Indicators of Insomnia Disorder.},
journal = {Journal of integrative neuroscience},
volume = {23},
number = {9},
pages = {180},
doi = {10.31083/j.jin2309180},
pmid = {39344239},
issn = {0219-6352},
support = {QN2019124//Anhui University of Science and Technology university-level project/ ; YZ2023H1A002//Anhui University of Science and Technology medical special cultivation project/ ; },
mesh = {Humans ; *Chitinase-3-Like Protein 1/blood ; Male ; Female ; *Sleep Initiation and Maintenance Disorders/blood/metabolism ; Adult ; Middle Aged ; *Telomere/metabolism ; Biomarkers/blood ; Leukocytes/metabolism ; },
abstract = {OBJECTIVE: To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder.

METHODS: A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length.

RESULTS: People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively.

CONCLUSIONS: Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms.},
}

Humans
*Chitinase-3-Like Protein 1/blood
Male
Female
*Sleep Initiation and Maintenance Disorders/blood/metabolism
Adult
Middle Aged
*Telomere/metabolism
Biomarkers/blood
Leukocytes/metabolism

@article {pmid39344121,
year = {2024},
author = {Li, Z and Wang, M and Zeng, S and Wang, Z and Ying, Y and Chen, Q and Zhang, C and He, W and Sheng, C and Wang, Y and Zhang, Z and Xu, C and Wang, H},
title = {Investigating the Shared Genetic Architecture Between Leukocyte Telomere Length and Prostate Cancer.},
journal = {The world journal of men's health},
volume = {},
number = {},
pages = {},
doi = {10.5534/wjmh.240062},
pmid = {39344121},
issn = {2287-4208},
support = {81772720/NNSFC/National Natural Science Foundation of China/China ; 81972391/NNSFC/National Natural Science Foundation of China/China ; 82172871/NNSFC/National Natural Science Foundation of China/China ; 2021008149//Naval Medical University/China ; 2020YXK019//Naval Medical University/China ; },
abstract = {PURPOSE: Evidence of an association between leukocyte telomere length (LTL) and prostate cancer (PCa) is accumulating; however, their shared genetic basis remains unclear.

MATERIALS AND METHODS: Using summary statistics obtained from the genome-wide association study (GWAS), we quantified the global and local genetic correlations between two traits. Subsequently, we identified potential pleiotropic loci, common tissue-enriched regions, and risk gene loci while inferring assumed causal relationships.

RESULTS: Our study demonstrated a global genetic correlation between LTL and PCa (genetic correlation=0.066, p=0.017), which was further confirmed in local genomic regions. Cross-trait GWAS meta-analysis revealed 44 shared loci, including 10 novel pleiotropic single nucleotide polymorphisms appearing concurrently in significant local genetic correlation regions. Notably, two new loci (rs9419958; rs3730668) were additionally validated to co-localize. For the first time, we identified a significant shared genetic enrichment of both traits in the small intestine tissue at the terminal ileum, with functional genes in this region affecting both LTL and PCa. Concurrently, Mendelian randomization analysis indicated a positive causal relationship between LTL and PCa.

CONCLUSIONS: In conclusion, our study makes a significant contribution to the ongoing debate concerning the potential association between longer LTL and a higher risk of PCa. Additionally, we provide new evidence for the development of therapeutic targets for PCa and propose new directions for future risk prediction in this regard.},
}

@article {pmid39342869,
year = {2024},
author = {Kyriacou, E and Lingner, J},
title = {TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.},
journal = {Current opinion in cell biology},
volume = {91},
number = {},
pages = {102437},
doi = {10.1016/j.ceb.2024.102437},
pmid = {39342869},
issn = {1879-0410},
abstract = {TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1. Telomeric R-loops interfere with replication fork progression, stimulating a switch of telomere maintenance from semiconservative DNA replication to homology-directed repair (HDR). The latter mechanism is exploited by a subset of cancer cells that lack telomerase, referred to as ALT. In addition, TERRA stimulates HDR at short telomeres during aging, delaying cellular senescence. During carcinogenesis, when cells with eroded telomeres enter replicative crisis, TERRA acts as a signaling molecule to mediate autophagic cell death.},
}

@article {pmid39339711,
year = {2024},
author = {Boccardi, V and Polom, J},
title = {Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.},
journal = {Nutrients},
volume = {16},
number = {18},
pages = {},
doi = {10.3390/nu16183111},
pmid = {39339711},
issn = {2072-6643},
mesh = {Humans ; Female ; *Telomere ; *Aging/physiology ; *Nutritional Status ; *Beauty ; Women's Health ; Quality of Life ; Longevity ; Healthy Aging ; Life Style ; Diet ; },
abstract = {Women typically outlive men, yet they often experience greater frailty and a higher incidence of chronic diseases as they age. By exploring the biological foundations of aging, with a particular focus on telomere dynamics, this manuscript aims to describe how dietary and lifestyle choices can significantly influence the aging process. The review comprehensively examines current research, underscoring the power of nutrition to counteract age-related changes, support healthy aging, and maintain vitality and beauty in women. The exploration of telomeres-the protective caps at the ends of chromosomes-reveals how they serve as markers of cellular aging and are potential targets for interventions aimed at enhancing women's longevity and quality of life. This study also emphasizes the importance of sex-specific approaches and precision medicine in understanding the unique health challenges women face as they age. By proposing targeted strategies, the review seeks to address these challenges, offering insights into preventive measures that can foster resilience, promote well-being, and extend healthy life expectancy in women. Ultimately, this work provides a sophisticated understanding of the aging process in women, highlighting the pivotal role of tailored interventions in preserving both health and beauty.},
}

Humans
Female
*Telomere
*Aging/physiology
*Nutritional Status
*Beauty
Women's Health
Quality of Life
Longevity
Healthy Aging
Life Style
Diet

@article {pmid39338301,
year = {2024},
author = {Mantadaki, AE and Baliou, S and Linardakis, M and Vakonaki, E and Tzatzarakis, MN and Tsatsakis, A and Symvoulakis, EK},
title = {Quercetin Intake and Absolute Telomere Length in Patients with Type 2 Diabetes Mellitus: Novel Findings from a Randomized Controlled Before-and-After Study.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/ph17091136},
pmid = {39338301},
issn = {1424-8247},
abstract = {Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole 'picture' remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio ≥ 2.44; p < 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin.},
}

@article {pmid39335189,
year = {2024},
author = {Fabiani, R and Chiavarini, M and Rosignoli, P and Giacchetta, I},
title = {Leucocyte Telomere Length and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies.},
journal = {Cancers},
volume = {16},
number = {18},
pages = {},
doi = {10.3390/cancers16183218},
pmid = {39335189},
issn = {2072-6694},
abstract = {Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk of lung cancer associated with LTL. The literature search was performed on PubMed, Web of Science, and Scopus databases through May 2024. A random-effects model was used to calculate the pooled risk. Heterogeneity was assessed using I[2] and Cochran's Q statistic. Begg's and Egger's tests were used to detect publication bias. Based on 8055 lung cancer cases and 854,653 controls (nine prospective studies), longer LTL was associated with a significant 42% increment in all types of lung cancer risk (OR 1.42, 95% CI 1.24-1.63). The effect was even more evident for adenocarcinomas (OR 1.98, 95% CI 1.69-2.31), while no association was observed for squamous cell carcinoma (OR 0.87, 95% CI 0.72-1.06). Significantly, no association was found for current smokers (OR 1.08, 95% CI 0.90-1.30), while it remained high for both never-smokers (OR 1.92, 95% CI 1.62-2.28) and former smokers (OR 1.34, 95% CI 1.11-1.62). No significant publication bias was evidenced. Longer LTL is associated with an increment in lung cancer risk particularly in never-smoker subjects.},
}

@article {pmid39333471,
year = {2024},
author = {Olagunju, TA and Rosen, BD and Neibergs, HL and Becker, GM and Davenport, KM and Elsik, CG and Hadfield, TS and Koren, S and Kuhn, KL and Rhie, A and Shira, KA and Skibiel, AL and Stegemiller, MR and Thorne, JW and Villamediana, P and Cockett, NE and Murdoch, BM and Smith, TPL},
title = {Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8277},
pmid = {39333471},
issn = {2041-1723},
support = {USDA-NIFA-2021-67016-33416//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; IDA01566//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; 3040-31000-104-000-D//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; 8042-31000-112-000-D//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; },
mesh = {Animals ; *Telomere/genetics ; Cattle/genetics ; Sheep/genetics ; *Y Chromosome/genetics ; Male ; Centromere/genetics ; Evolution, Molecular ; Genome/genetics ; Female ; },
abstract = {Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.},
}

Animals
*Telomere/genetics
Cattle/genetics
Sheep/genetics
*Y Chromosome/genetics
Male
Centromere/genetics
Evolution, Molecular
Genome/genetics
Female

@article {pmid39332705,
year = {2024},
author = {da Cruz, NFS and Sengillo, JD and Shah, SM and López-Font, FJ and Negron, CI and Berrocal, AM},
title = {Telomere Biology Disorders: Report on Clinical and Angiographic Findings.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2024.09.011},
pmid = {39332705},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate the retinal vasculature in pediatric patients with telomere biology disorders (TBD).

DESIGN: Retrospective consecutive case series.

SUBJECTS: Pediatric patients with a diagnosis of TBD who underwent widefield fluorescein angiography (FA).

METHODS: Electronic medical records of pediatric patients with TBD at a tertiary referral eye center were reviewed from January 2019 to July 2023. Vascular phenotype was assessed by reviewing FA images.

MAIN OUTCOMES MEASURES: Incomplete peripheral vascularization, aneurysmal dilatation, terminal arborization, anastomotic loops, capillary dropout, neovascularization, tortuosity, leakage from tractional membranes, and blockage from hemorrhage.

RESULTS: Fourteen eyes from 7 patients were included. All patients were genetically confirmed for TBD. The most common genetic variants were in CTC1 (5 patients; 71.4%), ACD (1 patient; 14.3%), and RTEL1 (1 patient; 14.3%). On FA, the most common findings were incomplete peripheral vascularization (14 eyes, 100%), aneurysmal dilatation (12 eyes, 85.7%), terminal arborization (12 eyes, 85.7%), anastomotic loops (12 eyes, 85.7%), capillary dropout (10 eyes, 71.4%), and neovascularization (9 eyes, 64.3%). Regarding treatment, laser photocoagulation (14 eyes, 100%), intravitreal bevacizumab injection (13 eyes, 92.6%), and sub-tenon's Kenalog (11 eyes, 78.6%) were utilized. All patients managed with laser photocoagulation and/or bevacizumab required multiple treatments.

CONCLUSION: Our study describes a spectrum of vascular changes evidenced by widefield FA in pediatric patients with genetically confirmed TBD. Although further research is warranted to fully understand the etiology of these subtle vascular anomalies, widefield FA should be conducted in patients with genetically confirmed or suspected TBD.},
}

@article {pmid39331358,
year = {2024},
author = {Mattiolo, P and Bevere, M and Mafficini, A and Verschuur, AVD and Calicchia, M and Hackeng, WM and Simbolo, M and Paiella, S and Dreijerink, KMA and Landoni, L and Pedron, S and Cingarlini, S and Salvia, R and Milella, M and Lawlor, RT and Valk, GD and Vriens, MR and Scarpa, A and Brosens, LA and Luchini, C},
title = {Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres).},
journal = {Endocrine pathology},
volume = {},
number = {},
pages = {},
pmid = {39331358},
issn = {1559-0097},
support = {26343, 28054, 29829//Associazione Italiana per la Ricerca sul Cancro/ ; 26343, 28054, 29829//Associazione Italiana per la Ricerca sul Cancro/ ; 2020-1 12978//KWF Kankerbestrijding/ ; 2020-1 12978//KWF Kankerbestrijding/ ; J38D19000690001//Fondazione Italiana per la ricerca sulle Malattie del Pancreas/ ; J38D19000690001//Fondazione Italiana per la ricerca sulle Malattie del Pancreas/ ; (RF CO-2019-12369662: CUP: B39C21000370001//Ministero della Salute/ ; },
abstract = {Glucagonomas are functioning pancreatic neuroendocrine tumors (PanNETs) responsible for glucagonoma syndrome. This study aims to shed light on the clinicopathological and molecular features of these neoplasms. Six patients with glucagonomas were identified. All neoplasms were investigated with immunohistochemistry for neuroendocrine markers (Synaptophysin, Chromogranin-A), ATRX, DAXX, ARX, and PDX1 transcription factors. Fluorescent in situ hybridization (FISH) for assessing alternative lengthening of telomeres (ALT), and next-generation sequencing (NGS) for molecular profiling were performed. All cases were large single masses (mean size of 8.2 cm), with necrolytic migratory erythema as the most common symptom (6/6 cases, 100%). All neoplasms were well-differentiated G1 tumors, except one case that was G2. The tumors consistently showed classic/conventional histomorphology, with solid-trabecular and nested architecture. Lymphatic and vascular invasion (6/6, 100%), perineural infiltration (4/6, 66.6%), and nodal metastasis (4/6, 66.6%) were frequently observed. Transcription factors expression showed strong ARX expression in all tumors, and PDX1 expression in 5/6 cases (83.3%), indicating co-occurring alpha- and beta-cell differentiation. NGS showed recurrent somatic MEN1 and ATRX/DAXX biallelic inactivation. Cases with ATRX or DAXX mutations also showed matched loss of ATRX or DAXX protein expression and ALT. One case harbored somatic MUTYH inactivation and showed a high tumor mutational burden (TMB, 41.0 mut/Mb). During follow-up, one patient died of the disease, and four patients developed distant metastasis. Pancreatic glucagonomas are distinct PanNETs with specific clinicopathological and molecular features, including histological aspects of biological aggressiveness, co-occurring alpha- and beta-cell differentiation, MEN1 and DAXX/ATRX mutations enrichment, and the possible presence of high-TMB as an actionable marker.},
}

@article {pmid39330362,
year = {2024},
author = {Chen, X and Wei, Y and Meng, G and Wang, M and Peng, X and Dai, J and Dong, C and Huo, G},
title = {Telomere-to-Telomere Haplotype-Resolved Genomes of Agrocybe chaxingu Reveals Unique Genetic Features and Developmental Insights.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {10},
number = {9},
pages = {},
doi = {10.3390/jof10090602},
pmid = {39330362},
issn = {2309-608X},
support = {JXXTCX202409//Collaborative Innovation Project of Modern Agricultural Research of Jiangxi Province/ ; 20212BBF61002, 20212BBF63013//Project of Science and Technology Department of Jiangxi Province/ ; JXXTCXBSJJ202213//Collaborative Innovation Project of Modern Agricultural Research of Jiangxi Province/ ; none//Crop Seeds Joint Research of Jiangxi Province/ ; CARS20//China Agriculture Research System/ ; },
abstract = {Agrocybe chaxingu is a widely cultivated edible fungus in China, which is rich in nutrients and medicinal compounds. However, the lack of a high-quality genome hinders further research. In this study, we assembled the telomere-to-telomere genomes of two sexually compatible monokaryons (CchA and CchB) derived from a primarily cultivated strain AS-5. The genomes of CchA and CchB were 50.60 Mb and 51.66 Mb with contig N50 values of 3.95 Mb and 3.97 Mb, respectively. Each contained 13 complete chromosomes with telomeres at both ends. The high mapping rate, uniform genome coverage, high LAI score, all BUSCOs with 98.5%, and all base accuracy exceeding 99.999% indicated the high level of integrity and quality of these two assembled genomes. Comparison of the two genomes revealed that approximately 30% of the nucleotide sequences between homologous chromosomes were non-syntenic, including 19 translocations, 36 inversions, and 15 duplications. An additional gene CchA_000467 was identified at the Mat A locus of CchA, which was observed exclusively in the Cyclocybe cylindracea species complex. A total of 613 (4.26%) and 483 (3.4%) unique genes were identified in CchA and CchB, respectively, with over 80% of these being hypothetical proteins. Transcriptomic analysis revealed that the expression levels of unique genes in CchB were significantly higher than those in CchA, and both CchA and CchB had unique genes specifically expressed at stages of mycelium and fruiting body. It was indicated that the growth and development of the A. chaxingu strain AS-5 required the coordinated action of two different nuclei, with CchB potentially playing a more significant role. These findings contributed to a more profound comprehension of the growth and developmental processes of basidiomycetes.},
}

@article {pmid39329317,
year = {2024},
author = {Naish, M},
title = {Bridging the gap: unravelling plant centromeres in the telomere-to-telomere era.},
journal = {The New phytologist},
volume = {},
number = {},
pages = {},
doi = {10.1111/nph.20149},
pmid = {39329317},
issn = {1469-8137},
support = {//School of the Biological Sciences, University of Cambridge/ ; },
abstract = {Centromeres are specific regions of the chromosomes that play a pivotal role in the segregation of chromosomes, by facilitating the loading of the kinetochore, which forms the link between the chromosomes to the spindle fibres during cell division. In plants and animals, these regions often form megabase-scale loci of tandemly repeated DNA sequences, which have presented a challenge to genomic studies even in model species. The functional designation of centromeres is determined epigenetically by the incorporation of a centromere-specific variant of histone H3. Recent developments in long-read sequencing technology have allowed the assembly of these regions for the first time and have prompted a reassessment of fidelity of centromere function and the evolutionary dynamics of these regions.},
}

@article {pmid39329264,
year = {2024},
author = {Granger, SL and Sharma, R and Kaushik, V and Razzaghi, M and Honda, M and Gaur, P and Bhat, DS and Labenz, SM and Heinen, JE and Williams, BA and Tabei, SMA and Wlodarski, MW and Antony, E and Spies, M},
title = {Human hnRNPA1 reorganizes telomere-bound replication protein A.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae834},
pmid = {39329264},
issn = {1362-4962},
support = {R35GM131704/NH/NIH HHS/United States ; K08 DK134873/DK/NIDDK NIH HHS/United States ; CA078586/BC/NCI NIH HHS/United States ; },
abstract = {Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection.},
}

@article {pmid39324245,
year = {2024},
author = {Sánchez-González, JL and Juárez-Vela, R and Dutil Muñoz de la Torre, V and Andrés-Olivera, MDP and Martín-Vallejo, J and Morán-Bayón, Á and Gonçalves-Cerejeira, JI and Gestoso-Uzal, N and González-Sarmiento, R and Pérez, J},
title = {Effect of strength-based physical exercise on telomere length as a marker of premature ageing in patients with schizophrenia: study protocol for a pilot randomised controlled trial.},
journal = {BJPsych open},
volume = {10},
number = {5},
pages = {e162},
doi = {10.1192/bjo.2024.753},
pmid = {39324245},
issn = {2056-4724},
abstract = {BACKGROUND: Patients with schizophrenia die decades earlier than the general population. Among the factors involved in this mortality gap, evidence suggests a telomere length shortening in this clinical population, which is associated with premature ageing. Recent studies support the use of strength-based training exercise programmes to maintain, or even elongate, telomere length in healthy elderly populations. However, studies aiming at modifying telomere length in severe mental illnesses, such as schizophrenia, are still very scarce.

AIMS: To investigate the effect of a strength-based physical exercise programme on the telomere length of individuals with schizophrenia.

METHOD: We propose a pragmatic, randomised controlled trial including 40 patients aged ≥18 years, with a stable diagnosis of schizophrenia, attending the Complejo de Rehabilitación Psicosocial (CRPS, Psychosocial Rehabilitation Centre) in Salamanca, Spain. These patients will be randomly assigned (1:1) to either receive the usual treatment and rehabilitation programmes offered by CRPS (treatment-as-usual group) or these plus twice weekly sessions of an evidence-based, strength-based training exercise programme for 12 weeks (intervention group). The primary outcome will be effect on telomere length. Secondary outcomes will include impact on cognitive function, frailty and quality of life.

RESULTS: We expect to show the importance of implementing strength-based physical exercise programmes for patients with schizophrenia. We could find that such programmes induce biological and genetic changes that may lengthen life expectancy and decrease physical fragility.

CONCLUSIONS: We anticipate that our trial findings could contribute to parity of esteem for mental health, reducing premature ageing in patients with severe mental illnesses, such as schizophrenia.},
}

@article {pmid39317127,
year = {2024},
author = {Katerina, S},
title = {Telomeres and immunodeficiencies.},
journal = {Human immunology},
volume = {85},
number = {6},
pages = {111146},
doi = {10.1016/j.humimm.2024.111146},
pmid = {39317127},
issn = {1879-1166},
abstract = {The function of the immune system is highly dependent on cellular differentiation and clonal expansion of antigen-specific lymphocytes. Telomeres are conserved DNA-protein structures of linear chromosome termini. Telomere length has been investigated to be different in various lymphocyte subpopulations depending on their function and to change with aging. Association of accelerated telomere loss compared to matched controls has already been confirmed in many syndromes with immune dysregulation. Immunodeficiencies connected with dysfunction of telomere termini are dyskeratosis congenita, ICF syndrome (Immunodeficiency, centromeric instability and facial anomalies syndrome) genetic disorders involving DNA repair and disorders involving the VDJ recombination.},
}

@article {pmid39316766,
year = {2024},
author = {Gutierrez-Rodrigues, F and Groarke, EM and Thongon, N and Rodriguez-Sevilla, JJ and Bazzo Catto, LF and Niewisch, MR and Shalhoub, RN and McReynolds, LJ and Clé, DV and Patel, BA and Ma, X and Hironaka, D and Donaires, FS and Spitofsky, NR and Santana, BA and Lai, TP and Alemu, L and Kajigaya, S and Darden, I and Zhou, W and Browne, PV and Paul, S and Lack, J and Young, DJ and DiNardo, CD and Aviv, A and Ma, F and Michels de Oliveira, M and Azambuja, AP and Dunbar, CE and Olszewska, M and Olivier, E and Papapetrou, EP and Giri, N and Alter, BP and Bonfim, CMS and Wu, CO and Garcia-Manero, G and Savage, SA and Young, NS and Colla, S and Calado, RT},
title = {Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescuing and cancer mutations.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025023},
pmid = {39316766},
issn = {1528-0020},
abstract = {Telomere biology disorders (TBD), caused by pathogenic germline variants in telomere-related genes, present with multi-organ disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBD is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 TBD patients with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, and splicing factor genes associated with poorer overall survival. Chr1q+, and splicing factor or TP53 mutations significantly increased the risk of hematologic malignancies, regardless of the clonal burden. Chr1q+ and U2AF1S34 mutated clones were pre-malignant events associated with the secondary acquisition of mutations in genes related to hematologic malignancies. Like known effects of Chr1q+ and TP53-CH, functional studies demonstrated that U2AF1S34 mutations primarily compensated for aberrant upregulation of TP53 and interferon pathways in telomere-dysfunctional hematopoietic stem cells, highlighting the TP53 pathway as a canonical route of malignancy in TBD. In contrast, somatic POT1/PPM1D/TERTp-CH had distinct trajectories unrelated to cancer development. With implications beyond TBD, our data show that telomere dysfunction is a strong selective pressure for CH. In TBD, CH is a poor prognostic marker associated with worse overall survival. The identification of key regulatory pathways that drive clonal transformation in TBD allows the identification of patients at a higher risk of cancer development.},
}

@article {pmid39312382,
year = {2024},
author = {Song, T and Liu, J and Zhao, K and Li, S and Qiu, M and Zhang, M and Wang, H},
title = {The causal effect of telomere length on the risk of malignant lymphoma: A Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {38},
pages = {e39584},
pmid = {39312382},
issn = {1536-5964},
mesh = {*Mendelian Randomization Analysis/methods ; Humans ; *Genome-Wide Association Study ; Lymphoma/genetics/epidemiology ; Hodgkin Disease/genetics/epidemiology ; Telomere/genetics ; Risk Factors ; Lymphoma, Follicular/genetics/epidemiology ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; },
abstract = {Telomere length (TL) has been implicated in the risk assessment of numerous cancers in observational studies. Nevertheless, the relationship between TL and malignant lymphoma remains unclear, displaying inconsistent patterns across different studies. A summary dataset for genome-wide association study of TL and malignant lymphoma was acquired from the OpenGWAS website. An extensive 2-sample Mendelian randomization (MR) analysis was performed, encompassing various methodologies such as MR-Egger, weighted median, weighted mode, simple mode, and the primary method of inverse-variance weighting (IVW). Sensitivity evaluations were performed using the Cochran Q test, MR-Egger regression, and leave-one-out analysis. The main method IVW revealed that TL substantially increased the risk of Hodgkin lymphoma (HL; odds ratio [OR] = 2.135; 95% confidence interval [CI] = 1.181-3.859; P = .012). Both the IVW and weighted median methods indicated statistical associations between genetically predicted TL and other types of non-HL (OR = 1.671, 95% CI = 1.009-2.768, P = .045; OR = 2.310, 95% CI = 1.033-5.169, P = .042). However, there was no association between TL and diffuse large B-cell lymphoma, follicular lymphoma, or mature T/natural Killer-cell lymphoma, and sensitivity analysis revealed no heterogeneity or horizontal pleiotropy, indicating that the causal effect was robust. Our study shows that TL plays different roles in different types of lymphomas. A longer TL significantly increases the risk of HL and other types of non-HL.},
}

*Mendelian Randomization Analysis/methods
Humans
*Genome-Wide Association Study
Lymphoma/genetics/epidemiology
Hodgkin Disease/genetics/epidemiology
Telomere/genetics
Risk Factors
Lymphoma, Follicular/genetics/epidemiology
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide

@article {pmid39307671,
year = {2024},
author = {Lan, L and Zhang, R and Liang, Y and Chen, H and Zhao, H and Zhuo, X},
title = {Evaluating the Effect of Telomere Length on Oral and Oropharyngeal Cancer Risk Using Mendelian Randomization.},
journal = {International dental journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.identj.2024.07.1218},
pmid = {39307671},
issn = {1875-595X},
abstract = {INTRODUCTION: The aim of this study was to explore the causal relationship between telomere length and Oral and oropharyngeal cancers by using Mendelian randomization (MR) analysis.

METHODS: We carried out a 2-sample MR to examine the causal association between telomere length and Oral and oropharyngeal cancers. Two large genome-wide association studies (GWAS) were employed to identify single nucleotide polymorphisms (SNPs) as instrumental variables through statistical and biological approaches. The data on SNP-oral and oropharyngeal cancer risk factor associations were sourced from various consortia/UK Biobank. The inverse variance weighted (IVW) method was employed as the primary approach for overall causal estimation in MR, with sensitivity analyses conducted to assess potential confounding by pleiotropy, heterogeneity, and the leave-one-out analysis.

RESULTS: The statistically driven approach indicates limited evidence of a genetically causal effect of telomere length on the risk of oral cavity cancer (OR = 0.999, 95% CI 0.998-1.000, P = .100), oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.001, P = .650), combined oral and oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.000, P = .119) in Europeans. The biologically driven approach demonstrated consistent causal effects across all MR methods, thereby further strengthening the reliability of the results. Moreover, the MR-Egger (Q [df] 170.816 [130], P = .009) and inverse variance weighted methods (Q [df] 171.656 [131], P = .010) identified considerable heterogeneity among instrumental variable estimates in Oral cavity cancer, and no evidence of horizontal pleiotropy was detected.

CONCLUSIONS: No significant causal associations between telomere length and Oral and oropharyngeal cancers were found in this study.},
}

@article {pmid39297884,
year = {2024},
author = {Chen, Z and Vallega, KA and Wang, D and Quan, Z and Fan, S and Wang, Q and Leal, T and Ramalingam, SS and Sun, SY},
title = {Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer.},
journal = {The Journal of experimental medicine},
volume = {221},
number = {11},
pages = {},
doi = {10.1084/jem.20240435},
pmid = {39297884},
issn = {1540-9538},
support = {UG1 CA233259/NH/NIH HHS/United States ; /CA/NCI NIH HHS/United States ; },
mesh = {*Acrylamides/pharmacology/therapeutic use ; *Telomerase/genetics/metabolism/antagonists & inhibitors ; *Aniline Compounds/pharmacology/therapeutic use ; Humans ; *ErbB Receptors/genetics/antagonists & inhibitors/metabolism ; *Lung Neoplasms/drug therapy/genetics/pathology ; Animals ; *Telomere/metabolism/drug effects ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology ; *Mutation ; Cell Line, Tumor ; *Drug Resistance, Neoplasm/genetics/drug effects ; Mice ; Xenograft Model Antitumor Assays ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Antineoplastic Agents/pharmacology/therapeutic use ; Indoles ; Pyrimidines ; },
abstract = {The inevitable acquired resistance to osimertinib (AZD9291), an FDA-approved third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR activating or T790M resistant mutations, limits its long-term clinical benefit. Telomere maintenance via telomerase reactivation is linked to uncontrolled cell growth and is a cancer hallmark and an attractive cancer therapeutic target. Our effort toward understanding the action mechanisms, including resistance mechanisms, of osimertinib has led to the identification of a novel and critical role in maintaining c-Myc-dependent downregulation of hTERT, a catalytic subunit of telomerase, and subsequent inhibition of telomerase/telomere and induction of telomere dysfunction in mediating therapeutic efficacy of osimertinib. Consequently, osimertinib combined with the telomere inhibitor, 6-Thio-dG, which is currently tested in a phase II trial, effectively inhibited the growth of osimertinib-resistant tumors, regressed EGFRm NSCLC patient-derived xenografts, and delayed the emergence of acquired resistance to osimertinib, warranting clinical validation of this strategy to manage osimertinib acquired resistance.},
}

*Acrylamides/pharmacology/therapeutic use
*Telomerase/genetics/metabolism/antagonists & inhibitors
*Aniline Compounds/pharmacology/therapeutic use
Humans
*ErbB Receptors/genetics/antagonists & inhibitors/metabolism
*Lung Neoplasms/drug therapy/genetics/pathology
Animals
*Telomere/metabolism/drug effects
*Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
*Mutation
Cell Line, Tumor
*Drug Resistance, Neoplasm/genetics/drug effects
Mice
Xenograft Model Antitumor Assays
Protein Kinase Inhibitors/pharmacology/therapeutic use
Antineoplastic Agents/pharmacology/therapeutic use
Indoles
Pyrimidines

@article {pmid39303890,
year = {2024},
author = {Ma, K and Zhu, M and Zhang, A and Zuo, M and Huang, Y and Wan, Y and Tao, F and Sun, Y},
title = {Intergenerational continuation of parent-child separation and 1-year telomere length attrition among mother-offspring dyads in rural China: The moderating effects of resilience.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.09.098},
pmid = {39303890},
issn = {1573-2517},
abstract = {BACKGROUND: Although stressor exposure early in life was known risk factor for telomere length (TL) attrition, limited literature explored it across generations. Furthermore, the effects of resilience have rarely been examined. Here, we examined whether the effects of intergenerational parent-child separation on offspring 1-year TL attrition vary by the levels of resilience.

METHOD: In a sample of 342 mother-child dyads living in rural China, the intergenerational continuation of parent-child separation was defined as the two generations both experiencing parent-child separation from both parents for >6 months a year early in life assessed by the parent-reported questionnaire, whereas intergenerational discontinuity refers to parent-child separation exposed in one generation only. TL was measured at baseline (from June to November 2021) and 1-year later with children's buccal mucosa swabs, with resilience polygenic risk scores (PRS) evaluated based on 4 single-nucleotide variations in 4 resilience-related genes (OXTR, FKBP5, NPY, and TNF-α).

RESULTS: Among 342 mother-offspring dyads, 35 (10.2 %) experienced intergenerational continuation of parent-child separation, and 139 (40.6 %) were identified as discontinuous. Remarkably, a 0.12-point reduction in TL attrition was only associated with intergenerational continuation of parent-child separation (95 % CI: 0.04, 0.21, P < 0.01) but not discontinuity. Importantly, the association between intergenerational continuation of parent-child separation with accelerated TL attrition disappeared in offspring with high resilience PRS (β = 0.07, 95%CI: -0.06, 0.21).

CONCLUSION: Our findings highlight the importance of breaking the intergenerational cycle of parent-child separation and the moderating effects of resilience on TL attrition for children exposed to adversity.},
}

@article {pmid39303531,
year = {2024},
author = {Hailu, EM and Gao, X and Needham, BL and Seeman, T and Lewis, TT and Mujahid, MS},
title = {Associations between historical and contemporary measures of structural racism and leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA).},
journal = {Social science & medicine (1982)},
volume = {360},
number = {},
pages = {117229},
doi = {10.1016/j.socscimed.2024.117229},
pmid = {39303531},
issn = {1873-5347},
abstract = {BACKGROUND: We assessed the link between two manifestations of structural racism-historical redlining and contemporary racial residential segregation-and baseline and 10-year changes in leukocyte telomere length (LTL).

METHODS: We used data on Black and Hispanic/Latinx participants from Exams I and V of the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (N = 741, age range = 45-84 years). LTL was defined as the ratio of telomeric DNA to a single copy gene (T/S), and 10-year changes were adjusted for regression to the mean. We used 1930s Home Owners' Loan Corporation maps to assign three historical redlining grades (A&B: best/still desirable, C: declining, D: hazardous/redlined) to participants' neighborhoods (census-tracts) at baseline. The Getis-Ord Gi∗ statistic was used to evaluate census-tract level baseline residential segregation (low/moderate/high).

RESULTS: In mixed-effects regression models accounting for neighborhood clustering, individual characteristics, and current neighborhood environments, those living in highly segregated Black neighborhoods had 0.08 shorter baseline LTL (95% CI: -0.13, -0.04), than those residing in the least segregated neighborhoods. We did not find a relationship between residing in segregated neighborhoods and 10-year LTL changes, and associations between residing in historically redlined neighborhoods and both baseline LTL and 10-year changes in LTL were null. Across discriminatory disinvestment trajectories examined, individuals residing in highly segregated but non-redlined neighborhoods had 0.6 shorter baseline LTL than individuals residing in non-redlined neighborhoods with low/moderate segregation (95% CI: -0.12, -0.01).

CONCLUSIONS: Our results highlight the impact of racial segregation on cellular aging and underscore the need to ameliorate structural inequities within segregated neighborhoods.},
}

@article {pmid39303078,
year = {2024},
author = {Zhang, J and Liu, S and Zhao, S and Nie, Y and Zhang, Z},
title = {A telomere-to-telomere haplotype-resolved genome of white-fruited strawberry reveals the complexity of fruit colour formation of cultivated strawberry.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.14479},
pmid = {39303078},
issn = {1467-7652},
support = {RC220306//Shenyang Young and Middle-aged Science and Technology Innovation Talents Support Plan/ ; 2023020525-JH1/102-02//sub-project of Liaoning Province Germplasm Innovation Grain Storage and Technology Special Program/ ; 32130092//National Natural Science Foundation of China/ ; 32272681//National Natural Science Foundation of China/ ; },
}

@article {pmid39296266,
year = {2024},
author = {Froney, MM and Cook, CR and Cadiz, AM and Flinter, KA and Ledeboer, ST and Chan, B and Burris, LE and Hardy, BP and Pearce, KH and Wardell, AC and Golitz, BT and Jarstfer, MB and Pattenden, SG},
title = {A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.},
journal = {ACS pharmacology & translational science},
volume = {7},
number = {9},
pages = {2799-2819},
pmid = {39296266},
issn = {2575-9108},
abstract = {Telomeres are a protective cap that prevents chromosome ends from being recognized as double-stranded breaks. In somatic cells, telomeres shorten with each cell division due to the end replication problem, which eventually leads to senescence, a checkpoint proposed to prevent uncontrolled cell growth. Tumor cells avoid telomere shortening by activating one of two telomere maintenance mechanisms (TMMs): telomerase reactivation or alternative lengthening of telomeres (ALT). TMMs are a viable target for cancer treatment as they are not active in normal, differentiated cells. Whereas there is a telomerase inhibitor currently undergoing clinical trials, there are no known ALT inhibitors in development, partially because the complex ALT pathway is still poorly understood. For cancers such as neuroblastoma and osteosarcoma, the ALT-positive status is associated with an aggressive phenotype and few therapeutic options. Thus, methods that characterize the key biological pathways driving ALT will provide important mechanistic insight. We have developed a first-in-class phenotypic high-throughput screen to identify small-molecule inhibitors of ALT. Our screen measures relative C-circle level, an ALT-specific biomarker, to detect changes in ALT activity induced by compound treatment. To investigate epigenetic mechanisms that contribute to ALT, we screened osteosarcoma and neuroblastoma cells against an epigenetic-targeted compound library. Hits included compounds that target chromatin-regulating proteins and DNA damage repair pathways. Overall, the high-throughput C-circle assay will help expand the repertoire of potential ALT-specific therapeutic targets and increase our understanding of ALT biology.},
}

@article {pmid39292074,
year = {2024},
author = {Pérez-López, FR and Fernández-Alonso, AM and Ulloque-Badaracco, JR and Benites-Zapata, VA and Varikasuvu, SR},
title = {Telomere length in subjects with and without SARS-CoV-2 infection: a systematic review and meta-analysis.},
journal = {Revista da Associacao Medica Brasileira (1992)},
volume = {70},
number = {9},
pages = {e20240387},
doi = {10.1590/1806-9282.20240387},
pmid = {39292074},
issn = {1806-9282},
mesh = {Humans ; *COVID-19 ; *SARS-CoV-2 ; Telomere/genetics ; Telomere Shortening ; },
}

Humans
*COVID-19
*SARS-CoV-2
Telomere/genetics
Telomere Shortening

@article {pmid39291738,
year = {2024},
author = {Zheng, YL and Wu, X and Williams, M and Verhulst, S and Lin, J and Takahashi, Y and Ma, JX and Wang, Y},
title = {High-throughput single telomere analysis using DNA microarray and fluorescent in situ hybridization.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae812},
pmid = {39291738},
issn = {1362-4962},
support = {U01ES011786//National Institute of Health/ ; //Georgetown University/ ; },
abstract = {The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach was developed to measure the base-pair (bp) lengths of single telomeres. On average 32000 telomeres were measured per DNA sample with one microarray chip assaying 96 test DNA samples. Various telomere parameters, i.e. aTL and the frequency of short/long telomeres, were computed to delineate TL distribution. The intra-assay and inter-assay coefficient of variations of aTL ranged from 1.37% to 3.98%. The correlation coefficient (r) of aTL in repeated measurements ranged from 0.91 to 1.00, demonstrating high measurement precision. aTLs measured by DNA-array-FISH predicted aTLs measured by terminal restriction fragment (TRF) analysis with r ranging 0.87-0.99. A new accurate and high-throughput method has been developed to measure the bp lengths of single telomeres. The large number of single TL data provides an opportunity for an in-depth analysis of telomere dynamics and the complex relationship between telomere and age-related diseases.},
}

@article {pmid39291733,
year = {2024},
author = {Kim, S and Park, SH and Kang, N and Ra, JS and Myung, K and Lee, KY},
title = {Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae785},
pmid = {39291733},
issn = {1362-4962},
support = {IBS-R022-D1//Institute for Basic Science/ ; //National Research Foundation of Korea/ ; RS-2023-00251939//MSIT/ ; //National Research Foundation of Korea/ ; },
abstract = {Replication stresses are the major source of break-induced replication (BIR). Here, we show that in alternative lengthening of telomeres (ALT) cells, replication stress-induced polyubiquitinated proliferating cell nuclear antigen (PCNA) (polyUb-PCNA) triggers BIR at telomeres and the common fragile site (CFS). Consistently, depleting RAD18, a PCNA ubiquitinating enzyme, reduces the occurrence of ALT-associated promyelocytic leukemia (PML) bodies (APBs) and mitotic DNA synthesis at telomeres and CFS, both of which are mediated by BIR. In contrast, inhibiting ubiquitin-specific protease 1 (USP1), an Ub-PCNA deubiquitinating enzyme, results in an increase in the above phenotypes in a RAD18- and UBE2N (the PCNA polyubiquitinating enzyme)-dependent manner. Furthermore, deficiency of ATAD5, which facilitates USP1 activity and unloads PCNAs, augments recombination-associated phenotypes. Mechanistically, telomeric polyUb-PCNA accumulates SLX4, a nuclease scaffold, at telomeres through its ubiquitin-binding domain and increases telomere damage. Consistently, APB increase induced by Ub-PCNA depends on SLX4 and structure-specific endonucleases. Taken together, our results identified the polyUb-PCNA-SLX4 axis as a trigger for directing BIR.},
}

@article {pmid39287993,
year = {2024},
author = {Li, W and Chen, H and Yuan, X and Yao, Q and Zhang, M},
title = {Study of the role of leukocyte telomere length-related lncRNA NBR2 in Alzheimer's disease.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206107},
pmid = {39287993},
issn = {1945-4589},
abstract = {Alzheimer's Syndrome (AD) is a neurodegenerative disease that is prevalent in middle-aged and elderly people. As the disease progresses, patients gradually lose the ability to take care of themselves, which brings a heavy burden to the family. There is a link between leukocyte telomere length (LTL) and cognitive ability. To search for possible pathogenic mechanisms and potential therapeutic agents, we demonstrated a causal link between LTL and AD using Mendelian randomization analysis (MR). The expression of the target gene NBR2 and the downstream mRNA GJA1 and GJA1-related genes, pathway enrichment, and association with immune cells were further explored. Using the gene cluster-drug target interaction network, we obtained potential therapeutic drugs. Our study provides evidence for a causal link between AD and LTL, suggesting medicines that may treat and alleviate AD symptoms.},
}

@article {pmid39284832,
year = {2024},
author = {Zhao, J and Yang, K and Lu, Y and Zhou, L and Fu, H and Feng, J and Wu, J},
title = {Proteomic Mendelian randomization to identify protein biomarkers of telomere length.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {21594},
pmid = {39284832},
issn = {2045-2322},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Biomarkers/blood ; *Genome-Wide Association Study ; *Quantitative Trait Loci ; *Proteomics/methods ; Telomere Homeostasis ; Telomere/metabolism/genetics ; Proteome/metabolism ; Blood Proteins/genetics/metabolism ; Telomere Shortening ; },
abstract = {Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein-protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.},
}

Humans
*Mendelian Randomization Analysis
*Biomarkers/blood
*Genome-Wide Association Study
*Quantitative Trait Loci
*Proteomics/methods
Telomere Homeostasis
Telomere/metabolism/genetics
Proteome/metabolism
Blood Proteins/genetics/metabolism
Telomere Shortening

@article {pmid39283687,
year = {2024},
author = {Yin, D and Chen, C and Lin, D and Hua, Z and Ying, C and Zhang, J and Zhao, C and Liu, Y and Cao, Z and Zhang, H and Wang, C and Liang, L and Xu, P and Jian, J and Liu, K},
title = {Telomere-to-telomere gap-free genome assembly of the endangered Yangtze finless porpoise and East Asian finless porpoise.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae067},
pmid = {39283687},
issn = {2047-217X},
support = {2021YFD1200304//National Key Research and Development of China/ ; },
mesh = {*Porpoises/genetics ; *Telomere/genetics ; Animals ; *Genome ; Endangered Species ; Phylogeny ; Genomics/methods ; East Asian People ; },
abstract = {BACKGROUND: The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) and the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri, EFP) are 2 subspecies of the narrow-ridged finless porpoise that live in freshwater and saltwater, respectively. The main objective of this study was to provide contiguous chromosome-level genome assemblies for YFP and EFP.

RESULTS: Here, we generated and upgraded the genomes of YFP and EFP at the telomere-to-telomere level through the integration of PacBio HiFi long reads, ultra-long ONT reads, and Hi-C sequencing data with a total size of 2.48 Gb and 2.50 Gb, respectively. The scaffold N50 of 2 genomes was 125.12 Mb (YFP) and 128 Mb (EFP) with 1 contig for 1 chromosome. The telomere repeat and centromere position were clearly identified in both YFP and EFP genomes. In total, 5,480 newfound genes were detected in the YFP genome, including 56 genes located in the newly identified centromere regions. Additionally, synteny blocks, structural similarities, phylogenetic relationships, gene family expansion, and inference of selection were studied in connection with the genomes of other related mammals.

CONCLUSIONS: Our research findings provide evidence for the gradual adaptation of EFP in a marine environment and the potential sensitivity of YFP to genetic damage. Compared to the 34 cetacean genomes sourced from public databases, the 2 new assemblies demonstrate superior continuity with the longest contig N50 and scaffold N50 values, as well as the lowest number of contigs. The improvement of telomere-to-telomere gap-free reference genome resources supports conservation genetics and population management for finless porpoises.},
}

*Porpoises/genetics
*Telomere/genetics
Animals
*Genome
Endangered Species
Phylogeny
Genomics/methods
East Asian People

@article {pmid39279436,
year = {2024},
author = {Thompson, AS and Niewisch, MR and Giri, N and McReynolds, LJ and Savage, SA},
title = {Germline RTEL1 Variants in Telomere Biology Disorders.},
journal = {American journal of medical genetics. Part A},
volume = {},
number = {},
pages = {e63882},
doi = {10.1002/ajmg.a.63882},
pmid = {39279436},
issn = {1552-4833},
support = {//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
abstract = {Rare germline variation in regulator of telomere elongation helicase 1 (RTEL1) is associated with telomere biology disorders (TBDs). Biallelic RTEL1 variants result in childhood onset dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome whereas heterozygous individuals usually present later in life with pulmonary fibrosis or bone marrow failure. We compiled all TBD-associated RTEL1 variants in the literature and assessed phenotypes and outcomes of 44 individuals from 14 families with mono- or biallelic RTEL1 variants enrolled in clinical trial NCT00027274. Variants were classified by adapting ACMG-AMP guidelines using clinical information, telomere length, and variant allele frequency data. Compared with heterozygotes, individuals with biallelic RTEL1 variants had an earlier age at diagnosis (median age 35.5 vs. 5.1 years, p < 0.01) and worse overall survival (median age 66.5 vs. 22.9 years, p < 0.001). There were 257 unique RTEL1 variants reported in 47 publications, and 209 had a gnomAD minor allele frequency <1%. Only 38.3% (80/209) met pathogenic/likely pathogenic criteria. Notably, 8 of 209 reported disease-associated variants were benign or likely benign and the rest were variants of uncertain significance. Given the considerable differences in outcomes of TBDs associated with RTEL1 germline variants and the extent of variation in the gene, systematic functional studies and standardization of variant curation are urgently needed to inform clinical management.},
}

@article {pmid39279213,
year = {2024},
author = {Maillet, F and Galimard, JE and Borie, R and Lainey, E and Larcher, L and Passet, M and Plessier, A and Leblanc, T and Terriou, L and Lebon, D and Alcazer, V and Cathebras, P and Loschi, M and Wadih, AC and Marcais, A and Marceau-Renaut, A and Couque, N and Lioure, B and Soulier, J and Ba, I and Socié, G and Peffault de Latour, R and Kannengiesser, C and Sicre de Fontbrune, F},
title = {Haematological features of telomere biology disorders diagnosed in adulthood: A French nationwide study of 127 patients.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19767},
pmid = {39279213},
issn = {1365-2141},
abstract = {Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra-haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety-three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow-up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4-year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus-related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high-risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome.},
}

@article {pmid39267212,
year = {2024},
author = {Rivera, AS and Chao, CR and Hechter, RC},
title = {Disparities in Telomere length by Sexual Orientation in Adults from the Genetic Epidemiology Research on Aging Cohort.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae352},
pmid = {39267212},
issn = {1476-6256},
abstract = {The weathering hypothesis proposes that marginalized people experience faster biologic aging due to cumulative stress which translates to chronic disease disparities. We assessed telomere length (TL) differences, an aging biomarker, by sexual orientation (bisexual, gay/lesbian, straight) among 102,258 individuals enrolled in the Resource for Genetic Epidemiology Research on Aging Cohort during 2008 through 2011 (mean age of 60.6 years, 58% female, and 7.6% bisexual/gay/lesbian). We used linear models to estimate differences in telomere length, stratified by sex/gender and adjusted for age (at salivary sample) and socio-demographic variables and Kitagawa-Blinder-Oaxaca decomposition to quantify contributions of participant factors on TL differences. Among females, there was no significant difference in age-adjusted telomere length by sexual orientation after adjustment for socio-demographics (ref: straight; bisexual 0.007, 95%CI: -0.03 to 0.04; lesbian: 0.005, 95%CI: -0.02 to 0.03). Among males, only gay (-0.04, 95%CI: -0.06 to -0.02) but not bisexual (-0.02, 95%CI: -0.06 to 0.02) men had significantly shorter age-adjusted telomere length compared to straight men after adjusting for socio-demographic variables. Decomposition analysis identified ever smoking and marital status as significant drivers of the gay-straight disparity. Studies confirming our findings are needed and the implications of shorter telomeres on gay men's health requires further investigation.},
}

@article {pmid39275278,
year = {2024},
author = {de Jaeger, C and Kruiskamp, S and Voronska, E and Lamberti, C and Baramki, H and Beaudeux, JL and Cherin, P},
title = {A Natural Astragalus-Based Nutritional Supplement Lengthens Telomeres in a Middle-Aged Population: A Randomized, Double-Blind, Placebo-Controlled Study.},
journal = {Nutrients},
volume = {16},
number = {17},
pages = {},
doi = {10.3390/nu16172963},
pmid = {39275278},
issn = {2072-6643},
mesh = {Humans ; Double-Blind Method ; Middle Aged ; *Dietary Supplements ; Male ; Female ; *Astragalus Plant/chemistry ; *Telomere/drug effects ; *Telomerase/metabolism ; Telomere Homeostasis/drug effects ; Telomere Shortening/drug effects ; },
abstract = {Telomeres are ribonucleoprotein structures that form a protective buffer at the ends of chromosomes, maintaining genomic integrity during the cell cycle. A decrease in average telomere length is associated with with age and with aging-related diseases such as cancer and cardiovascular disease. In this study, we conducted a randomized, double-blind, placebo-controlled trial over six months to compare the effects of the Astragalus-based supplement versus a placebo on telomere length (TL) in 40 healthy volunteers (mean age 56.1 ± 6.0 years). Twenty subjects received the supplement, and 20 received placebo capsules. All participants completed the study, and no adverse side effects were reported at six months. Subjects taking the Astragalus-based supplement exhibited significantly longer median TL (p = 0.01) and short TL (p = 0.004), along with a lower percentage of short telomeres, over the six-month period, while the placebo group showed no change in TL. This trial confirmed that the supplement significantly lengthens both median and short telomeres by increasing telomerase activity and reducing the percentage of short telomeres (<3 Kbp) in a statistically and possibly clinically significant manner. These results align with a previous open prospective trial, which found no toxicity associated with the supplement's intake. These findings suggest that this Astragalus-based supplement warrants further investigation for its potential benefits in promoting health, extending life expectancy, and supporting healthy aging.},
}

Humans
Double-Blind Method
Middle Aged
*Dietary Supplements
Male
Female
*Astragalus Plant/chemistry
*Telomere/drug effects
*Telomerase/metabolism
Telomere Homeostasis/drug effects
Telomere Shortening/drug effects

@article {pmid39273401,
year = {2024},
author = {Dratwa-Kuzmin, M and Hadra, BA and Oguz, F and Ogret, Y and Constantinescu, I and Apostol, D and Talangescu, A and Constantinescu, AE and Maruntelu, I and Kościńska, K and Lukanov, T and Naumova, E and Bogunia-Kubik, K},
title = {Telomere Length, HLA, and Longevity-Results from a Multicenter Study.},
journal = {International journal of molecular sciences},
volume = {25},
number = {17},
pages = {},
doi = {10.3390/ijms25179457},
pmid = {39273401},
issn = {1422-0067},
mesh = {Humans ; *Longevity/genetics ; Aged ; Middle Aged ; Male ; Adult ; Female ; Aged, 80 and over ; Adolescent ; *HLA Antigens/genetics ; Young Adult ; Telomere/genetics ; Alleles ; Telomere Homeostasis ; Aging/genetics/immunology ; Haplotypes ; },
abstract = {Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65-99 years) and ethnically matched young group (age 18-64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.},
}

Humans
*Longevity/genetics
Aged
Middle Aged
Male
Adult
Female
Aged, 80 and over
Adolescent
*HLA Antigens/genetics
Young Adult
Telomere/genetics
Alleles
Telomere Homeostasis
Aging/genetics/immunology
Haplotypes

@article {pmid39265426,
year = {2024},
author = {Edzie, J and Alcala, C and Bloomquist, TR and Gutierrez-Avila, I and Just, AC and Midya, V and Téllez Rojo, MM and Estrada-Gutierrez, G and Wright, RJ and Wright, RO and Baccarelli, AA and Rosa, MJ},
title = {Prenatal and early life exposure to fine particulate matter and telomere length in early childhood.},
journal = {International journal of hygiene and environmental health},
volume = {263},
number = {},
pages = {114447},
doi = {10.1016/j.ijheh.2024.114447},
pmid = {39265426},
issn = {1618-131X},
abstract = {BACKGROUND: Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences.

METHODS: Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification.

RESULTS: In trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (β: 4.34, 95%CI [0.42, 8.42], per 5 μg/m[3] increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (β: 7.12, [95%CI: 0.98, 13.6] and β: 1.43 [95%CI: -3.46, 6.57]) per 5 μg/m[3] increase respectively.

CONCLUSION: Second trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.},
}

@article {pmid39261898,
year = {2024},
author = {Zhao, W and Li, B and Zhang, M and Zhou, P and Zhu, Y},
title = {As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures.},
journal = {World journal of surgical oncology},
volume = {22},
number = {1},
pages = {245},
pmid = {39261898},
issn = {1477-7819},
support = {PW2023A-18//Pudong New Area Health Research General Project/ ; PWRd2023-10//Pudong New District Health Committee Discipline Leader Program/ ; },
abstract = {BACKGROUND: Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs.

METHODS: We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model's prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR.

RESULTS: We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we've discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment.

CONCLUSION: As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.},
}

@article {pmid39256983,
year = {2024},
author = {Musa, I and Yang, N and Breslin, J and Paulden, O and Geliebter, J and Tiwari, R and Li, XM},
title = {Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.},
journal = {Integrative cancer therapies},
volume = {23},
number = {},
pages = {15347354241267979},
doi = {10.1177/15347354241267979},
pmid = {39256983},
issn = {1552-695X},
mesh = {Humans ; *Multiple Myeloma/drug therapy ; Cell Line, Tumor ; *Telomere/drug effects/metabolism ; *Tumor Suppressor Protein p53/metabolism ; *Cannabinoids/pharmacology ; *Telomerase/metabolism ; Cell Survival/drug effects ; NF-kappa B/metabolism ; Immunoglobulin E ; Immunoglobulin G ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; },
abstract = {Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.},
}

Humans
*Multiple Myeloma/drug therapy
Cell Line, Tumor
*Telomere/drug effects/metabolism
*Tumor Suppressor Protein p53/metabolism
*Cannabinoids/pharmacology
*Telomerase/metabolism
Cell Survival/drug effects
NF-kappa B/metabolism
Immunoglobulin E
Immunoglobulin G
Cell Proliferation/drug effects
Gene Expression Regulation, Neoplastic/drug effects

@article {pmid39256139,
year = {2024},
author = {Pepke, ML and Hansen, SB and Limborg, MT},
title = {Telomere dynamics as mediators of gut microbiota-host interactions.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2024.08.003},
pmid = {39256139},
issn = {1879-3088},
abstract = {The highly proliferative gut tissue exhibits rapid telomere shortening with systemic effects on the host organism. Recent studies have demonstrated a bidirectionality in interactions between intestinal telomere length dynamics and the composition and activity of the gut microbiome thus linking processes of inflammation, dysbiosis and aging across different vertebrate species.},
}

@article {pmid39253978,
year = {2024},
author = {Carr, L and Norris, K and Parker, H and Nilsson-Takeuchi, A and Bryant, D and Amarasinghe, H and Kadalayil, L and Else, M and Pettitt, A and Hillmen, P and Schuh, A and Walewska, R and Baird, DM and Oscier, DG and Oakes, CC and Gibson, J and Pepper, C and Strefford, JC},
title = {Telomere length and DNA methylation epitype both provide independent prognostic information in CLL patients; data from the UK CLL4, ARCTIC and ADMIRE clinical trials.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19765},
pmid = {39253978},
issn = {1365-2141},
support = {Cancer Research UK Southampton Centre grant C34999/CRUK_/Cancer Research UK/United Kingdom ; ECRIN-M3 accelerator award C42023/A29370/CRUK_/Cancer Research UK/United Kingdom ; programme C2750/A23669/CRUK_/Cancer Research UK/United Kingdom ; },
}

@article {pmid39253325,
year = {2024},
author = {Liu, J and Pan, R},
title = {Genetic liability to human serum metabolites is causally linked to telomere length: insights from genome-wide Mendelian randomization and metabolic pathways analysis.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1458442},
doi = {10.3389/fnut.2024.1458442},
pmid = {39253325},
issn = {2296-861X},
abstract = {BACKGROUND: Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process.

METHODS: We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran's Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways.

RESULTS: We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length.

CONCLUSION: Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.},
}

@article {pmid39252519,
year = {2024},
author = {Furui, Y and Saito, S and Maruyama, Y and Okura, E and Hirabayashi, K and Tanaka, M and Nakazawa, Y},
title = {Successful ibrutinib treatment for pulmonary involvement in a post-transplant patient with inherited bone marrow failure syndrome and very short telomeres.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31314},
doi = {10.1002/pbc.31314},
pmid = {39252519},
issn = {1545-5017},
}

@article {pmid39250995,
year = {2024},
author = {Feng, Y and Guo, X and Luo, M and Sun, Y and Sun, L and Zhang, H and Zou, Y and Liu, D and Lu, H},
title = {GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {135240},
doi = {10.1016/j.ijbiomac.2024.135240},
pmid = {39250995},
issn = {1879-0003},
abstract = {The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.},
}

@article {pmid39250900,
year = {2024},
author = {Vostatek, R and Hohensinner, P and Schmaldienst, S and Lorenz, M and Klauser-Braun, R and Pabinger, I and Säemann, M and Ay, C and Königsbrügge, O},
title = {Telomere length is associated with increased risk of cardiovascular events in patients with end-stage kidney disease on hemodialysis.},
journal = {Cardiorenal medicine},
volume = {},
number = {},
pages = {1-16},
doi = {10.1159/000541112},
pmid = {39250900},
issn = {1664-5502},
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD), especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes.

METHODS: Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated 3P-MACE outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death.

RESULTS: In the cohort of 308 patients with ESKD (115 (37.3%) women, median (25th-75th percentile) age: 67.0 (56.8 - 76.0), the median telomere length was 1.51 kb (25th-75th percentile 0.6-3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95%CI 1.051-3.201, p=0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use.

CONCLUSION: Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events.},
}

@article {pmid39248546,
year = {2024},
author = {Nayır Büyükşahin, H and Emiralioğlu, N and Yalçın, E and Ozcan, HN and Oğuz, B and Utine, GE and Kiper, PÖ and Karaosmanoğlu, B and Orhan, D and Unal, S and Güzelkaş, İ and Alboğa, D and Doğru, D and Özçelik, U and Kiper, N},
title = {Two cases with undefined childhood interstitial lung disease: Can it be related to telomere variants?.},
journal = {Journal of paediatrics and child health},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpc.16666},
pmid = {39248546},
issn = {1440-1754},
}

@article {pmid39246285,
year = {2024},
author = {Piedrabuena, MA and Correale, J and Farez, MF and Rodríguez Murúa, S and Martínez Canyazo, C and Fiol, M and Marrodan, M and Ysrraelit, MC},
title = {Telomere length as a biomarker in multiple sclerosis.},
journal = {Multiple sclerosis (Houndmills, Basingstoke, England)},
volume = {},
number = {},
pages = {13524585241273054},
doi = {10.1177/13524585241273054},
pmid = {39246285},
issn = {1477-0970},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS).

OBJECTIVE: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects.

METHODS: Prospective 2-year study including two cohorts of young (18-35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay.

RESULTS: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm[3] and white matter volume 1.78 cm[3].

CONCLUSION: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS.},
}

@article {pmid39239547,
year = {2024},
author = {Huang, J and Feng, Y and Shi, Y and Shao, W and Li, G and Chen, G and Li, Y and Yang, Z and Yao, Z},
title = {Telomeres and telomerase in Sarcoma disease and therapy.},
journal = {International journal of medical sciences},
volume = {21},
number = {11},
pages = {2065-2080},
pmid = {39239547},
issn = {1449-1907},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Sarcoma/genetics/therapy/pathology ; *Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; Prognosis ; Mutation ; },
abstract = {Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.},
}

Humans
*Telomerase/genetics/metabolism
*Sarcoma/genetics/therapy/pathology
*Telomere/genetics/metabolism
*Telomere Homeostasis/genetics
Prognosis
Mutation

@article {pmid39237122,
year = {2024},
author = {Cao, Z and Li, Y and Wu, J},
title = {Causal linkage of psoriasis with ageing: Mendelian randomization and enrichment analysis towards telomere length and psoriasis.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgae115},
pmid = {39237122},
issn = {1469-0756},
support = {2019YFA0112100//National Key Research and Development Program of China/ ; },
abstract = {OBJECTIVE: Several studies demonstrated potential associations between the telomere length (TL) in leukocytes and psoriasis or psoriatic arthritis (PsA). This study aimed to investigate whether there was the causal genetic relationship between TL and psoriatic diseases bidirectionally.

METHODS: Two-sample univariable MR (UVMR) analysis was applied to explore the bidirectional causal association of TL with overall psoriasis, psoriasis vulgaris (PV) and PsA. Multivariable MR (MVMR) and the mediation effects analysis were applied to test whether the bidirectional associations between TLs and psoriasis were mediated by body mass index (BMI), alcohol, and smoking status.

RESULTS: According to the UVMR results, a negative causal impact of TL on the risk of overall psoriasis was found (OR = 0.775; 95% CI: 0.646-0.931; P = 6.36 × 10-3), and a similar trend was observed in the reversed direction for psoriasis-TL (IVW-β = -0.0097; 95% CI: -0.0170 to -0.0024; P = 9.12 × 10-3). There were also negative genetic associations between TL and PV bidirectionally. The independent association of genetically predicted TL and overall psoriasis persisted in the MVMR results controlled for BMI, smoking, and alcohol consumption (ORMVMR = 0.736; 95% CI: 0.597 to 0.907; P = 0.004). An independent significant association of genetic predisposition to PsA with TL was also found (βMVMR = 0.006; 95% CI: 0.001 to 0.012; P = 0.033). The mediation analysis showed that BMI partially mediated the reverse association between PSO and TL.

CONCLUSION: This MR study revealed an association between genetic indicators of shortened TL and risk of overall psoriasis and PV, and genetic predisposition to PsA was associated with longer TL. Key message What is already known on this topic?  Telomere length (TL) is acknowledged to reflect an individual's biological age but is also associated with dysregulated immune function and immunosenescence. The impact of aging on psoriasis is controversial. Existing evidence suggests that aging may influence pathological changes and clinical course but whether aging is an independent risk factor remains unclear. What this study adds?  The current study found an association between genetic indicators of shortened TL and the risk of overall psoriasis and psoriasis vulgaris (PV). There was a bidirectional link between genetically indicated overall psoriasis and shortened TL. A possible positive genetic association between PsA and TL was also found. How this study might affect research, practice, or policy?  Our study may provide evidence for TL as new diagnostic and therapeutic strategies in clinical practices for psoriasis. Greater efforts to psoriasis management may substantially reduce the aging attributable to TL shortening. Future large-scale GWAS and experimental studies are warranted to examine the mechanistic basis for links between TL and psoriasis to improve understanding and illuminate possible therapeutic targets for psoriatic disease.},
}

@article {pmid39235665,
year = {2024},
author = {Scarabino, D and Veneziano, L and Nethisinghe, S and Mantuano, E and Fiore, A and Granata, G and Solanky, N and Zanni, G and Cavalcanti, F and Corbo, RM and Giunti, P},
title = {Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.29976},
pmid = {39235665},
issn = {1531-8257},
support = {//Department of Health's National Institute for Health Research Biomedical Research Centre's/ ; //National Institute for Health Research University College London/ ; project 739510//European Reference Network for Rare Neurological Diseases/ ; MR/N028767/1//Medical Research Council Centre for Neurodevelopmental Disorders/ ; 2018/2019 grants//Sapienza University of Rome/ ; },
abstract = {BACKGROUND: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded GAA repeat in the first intron of the FXN gene.

OBJECTIVE: The aim of this study was to analyze leukocyte telomeres length (LTL) in FRDA to verify the possible relationships between LTL and disease progression. We investigated LTL in a cohort of FRDA biallelic patients (n = 61), heterozygous (n = 29), and age-matched healthy subjects (n = 87).

METHODS: LTL was measured by real-time polymerase chain reaction quantitative analysis (qPCR).

RESULTS: The results showed that before 35 years of age, leukocyte telomeres were longer in patients than in controls, whereas the reverse applies in patients above 36 years of age. Interestingly, LTL was greater than controls at any age in heterozygous subjects. This picture mirrors what has been previously observed in vitro in FRDA cultured fibroblasts, showing significantly longer telomeres at early passages because of activation of an alternative lengthening of telomeres (ALT)-like mechanism, but showing accelerated telomere shortening as population doubling increases. GAA1 repeat length is positively correlated with the LTL and negatively correlated with the age at blood sampling. The relationship of LTL with clinical parameters (cardiomyopathy, diabetes, dependence on a wheelchair) was also analyzed. Significantly shorter leukocyte telomeres were associated with the presence of cardiomyopathy, but not with diabetes and the dependence on a wheelchair.

CONCLUSIONS: Overall, the present study indicates that telomere length analysis in FRDA may be a relevant biomarker for following the stages of the disease. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid39234237,
year = {2024},
author = {Zhang, J and Xia, X and He, S},
title = {Deciphering the causal association and underlying transcriptional mechanisms between telomere length and abdominal aortic aneurysm.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1438838},
pmid = {39234237},
issn = {1664-3224},
mesh = {*Aortic Aneurysm, Abdominal/genetics/immunology ; Animals ; Mice ; Humans ; *Genome-Wide Association Study ; *Telomere Homeostasis ; *Telomere/genetics ; Mendelian Randomization Analysis ; Biomarkers ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Transcriptome ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA).

METHODS: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bi-directional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established.

RESULTS: Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers.

CONCLUSION: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA.},
}

*Aortic Aneurysm, Abdominal/genetics/immunology
Animals
Mice
Humans
*Genome-Wide Association Study
*Telomere Homeostasis
*Telomere/genetics
Mendelian Randomization Analysis
Biomarkers
Male
Disease Models, Animal
Mice, Inbred C57BL
Transcriptome
Genetic Predisposition to Disease

@article {pmid39231615,
year = {2024},
author = {Kochman, R and Ba, I and Yates, M and Pirabakaran, V and Gourmelon, F and Churikov, D and Lafaille, M and Kermasson, L and Hamelin, C and Marois, I and Jourquin, F and Braud, L and Bechara, M and Lainey, E and Nunes, H and Breton, P and Penhouet, M and David, P and Géli, V and Lachaud, C and Maréchal, A and Revy, P and Kannengiesser, C and Saintomé, C and Coulon, S},
title = {Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352032.124},
pmid = {39231615},
issn = {1549-5477},
abstract = {Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in RPA2 Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination. Using engineered knock-in cell lines, we found an accumulation of RPA at telomeres that did not trigger ATR activation but caused short and dysfunctional telomeres. Finally, both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening. Collectively, our study indicates that variants in RPA2 represent a novel genetic cause of TBDs. Our results further support the fundamental role of the RPA complex in regulating telomere length and stability in humans.},
}

@article {pmid39232410,
year = {2024},
author = {Konishi, K and Jacobs, EG and Aroner, S and De Vivo, I and Smith, B and Scribner-Weiss, B and Makris, N and Seitz-Holland, J and Remington, A and Aizley, H and Kubicki, M and Goldstein, JM},
title = {Leukocyte telomere length and memory circuitry and cognition in early aging: Impact of sex and menopausal status.},
journal = {Hormones and behavior},
volume = {165},
number = {},
pages = {105631},
doi = {10.1016/j.yhbeh.2024.105631},
pmid = {39232410},
issn = {1095-6867},
abstract = {Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.},
}

@article {pmid39231146,
year = {2024},
author = {Rönne-Petersén, L and Niemi, M and Walach, H and Lavebratt, C and Yang, LL and Gerdle, B and Ghafouri, B and Falkenberg, T},
title = {Exploring emotional well-being, spiritual, religious and personal beliefs and telomere length in chronic pain patients-A pilot study with cross-sectional design.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0308924},
doi = {10.1371/journal.pone.0308924},
pmid = {39231146},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Pilot Projects ; Cross-Sectional Studies ; Middle Aged ; *Chronic Pain/psychology ; Aged ; *Quality of Life ; *Spirituality ; Adult ; Emotions ; Telomere/genetics ; Surveys and Questionnaires ; Sweden ; Patient Reported Outcome Measures ; Depression/psychology ; Telomerase/metabolism/genetics ; Religion ; },
abstract = {Living with chronic pain is associated with substantial suffering and high societal costs. Patient reported outcomes (PROM's) and cellular ageing should be considered in pain management. The aim of this study was to explore correlations of PROM's and cellular ageing (telomere length [TL] and telomerase activity [TA]) amongst patients with chronic non-malignant pain. This was an explorative pilot study with cross-sectional design and recruitment was done at two pain rehabilitation facilities in Sweden, with inpatient setting/integrative care and outpatient setting/multimodal care, respectively. Eighty-four patients were enrolled by referral to pain rehabilitation in Sweden. The main outcome measures collected after admission in addition to TL and TA were the following PROMs: Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Hospital Anxiety and Depression Scale (HADS), Five Facets Mindfulness Questionnaire (FFMQ), WHO Quality of Life-Spiritual, Religious and Personal Beliefs (WHOQoL-SRPB) and EuroQol 5 Dimensions (EQ-5D). All the PROM's showed evidence of poor overall health status among the participants. TL correlated negatively with HADS score (r = -.219, p = .047) and positively with WHOQoL-SRPB (r = .224, p = .052). TL did not correlate with any of the pain measures. TA correlated positively with pain spread (r = .222, p = .049). A mediation of the direct effect of spiritual well-being on TL by anxiety and depression could be shown (b = 0.008; p = .045). The correlations between TL and SRPB and anxiety and depression suggest some importance of emotional and SRPB dimensions in pain management, with implications for cellular aging, which may warrant further study. Trial registration: ClinicalTrials.gov Identifier: NCT02459639.},
}

Humans
Male
Female
Pilot Projects
Cross-Sectional Studies
Middle Aged
*Chronic Pain/psychology
Aged
*Quality of Life
*Spirituality
Adult
Emotions
Telomere/genetics
Surveys and Questionnaires
Sweden
Patient Reported Outcome Measures
Depression/psychology
Telomerase/metabolism/genetics
Religion

@article {pmid39225247,
year = {2024},
author = {Noveir, SD and Galamgam, J and Pithadia, D and Truong, A and Hogeling, M and Cheng, CE},
title = {Reticulated pigmentary changes and Terry's nails in a patient with a TERT variant-associated telomere biology disorder.},
journal = {Pediatric dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/pde.15735},
pmid = {39225247},
issn = {1525-1470},
abstract = {Telomere biology disorders (TBD) are a complex set of inherited illnesses characterized by short telomeres. Dyskeratosis congenita (DC), which is now considered a severe TBD phenotype, is characterized by reticulated pigmentary changes, nail dystrophy, premalignant oral leukoplakia, and systemic involvement. This case describes a 2-year-old female with reticulated pigmentary changes and Terry's nails who was found to have a TERT variant and short telomeres; she lacked other mucocutaneous and systemic features of TBD. This report describes a unique clinical presentation of TBD and highlights the importance of upholding suspicion for TBD in individuals with limited or subtle features of classic DC.},
}

@article {pmid39224814,
year = {2024},
author = {Burrow, TA and Koneru, B and Macha, SJ and Sun, W and Barr, FG and Triche, TJ and Reynolds, CP},
title = {Prevalence of alternative lengthening of telomeres in pediatric sarcomas determined by the telomeric DNA C-circle assay.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1399442},
pmid = {39224814},
issn = {2234-943X},
abstract = {INTRODUCTION: Alternative lengthening of telomeres (ALT) occurs in sarcomas and ALT cancers share common mechanisms of therapy resistance or sensitivity. Telomeric DNA C-circles are self-primed circular telomeric repeats detected with a PCR assay that provide a sensitive and specific biomarker exclusive to ALT cancers. We have previously shown that 23% of high-risk neuroblastomas are of the ALT phenotype. Here, we investigate the frequency of ALT in Ewing's family sarcoma (EFS), rhabdomyosarcoma (RMS), and osteosarcoma (OS) by analyzing DNA from fresh frozen primary tumor samples utilizing the real-time PCR C-circle Assay (CCA).

METHODS: We reviewed prior publications on ALT detection in pediatric sarcomas. DNA was extracted from fresh frozen primary tumors, fluorometrically quantified, C-circles were selectively enriched by isothermal rolling cycle amplification and detected by real-time PCR.

RESULTS: The sample cohort consisted of DNA from 95 EFS, 191 RMS, and 87 OS primary tumors. One EFS and 4 RMS samples were inevaluable. Using C-circle positive (CC+) cutoffs previously defined for high-risk neuroblastoma, we observed 0 of 94 EFS, 5 of 187 RMS, and 62 of 87 OS CC+ tumors.

CONCLUSIONS: Utilizing the ALT-specific CCA we observed ALT in 0% of EFS, 2.7% of RMS, and 71% of OS. These data are comparable to prior studies in EFS and OS using less specific ALT markers. The CCA can provide a robust and sensitive means of identifying ALT in sarcomas and has potential as a companion diagnostic for ALT targeted therapeutics.},
}

@article {pmid39223261,
year = {2024},
author = {Sung, JY and Kim, SG and Park, SY and Kim, JR and Choi, HC},
title = {Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39223261},
issn = {2092-6413},
support = {2022R1A5A2018865//National Research Foundation of Korea (NRF)/ ; 2022R1I1A1A01055818//National Research Foundation of Korea (NRF)/ ; },
abstract = {Telomere dysfunction is a well-known molecular trigger of senescence and has been associated with various age-related diseases, including atherosclerosis. However, the mechanisms involved have not yet been elucidated, and the extent to which telomeres contribute to atherosclerosis is unknown. Therefore, we investigated the mechanism of metformin-induced telomere stabilization and the ability of metformin to inhibit vascular smooth muscle cell (VSMC) senescence caused by advanced atherosclerosis. The present study revealed that metformin inhibited the phenotypes of atherosclerosis and senescence in VSMCs. Metformin increased the phosphorylation of AMPK-dependent PGC-1α and thus increased telomerase activity and the protein level of TERT in OA-treated VSMCs. Mechanistically, the phosphorylation of AMPK and PGC-1α by metformin not only enhanced telomere function but also increased the protein level of TERT, whereas TERT knockdown accelerated the development of atherosclerosis and senescent phenotypes in OA-treated VSMCs regardless of metformin treatment. Furthermore, the in vivo results showed that metformin attenuated the formation of atherosclerotic plaque markers in the aortas of HFD-fed ApoE KO mice. Although metformin did not reduce plaque size, it inhibited the phosphorylation of the AMPK/PGC-1α/TERT signaling cascade, which is associated with the maintenance and progression of plaque formation, in HFD-fed ApoE KO mice. Accordingly, metformin inhibited atherosclerosis-associated phenotypes in vitro and in vivo. These observations show that the enhancement of telomere function by metformin is involved in specific signaling pathways during the progression of atherosclerosis. These findings suggest that telomere stabilization by metformin via the AMPK/p-PGC-1α pathway might provide a strategy for developing therapeutics against vascular diseases such as atherosclerosis.},
}

@article {pmid39222545,
year = {2024},
author = {Cao, X and Fang, L and Jiang, Y and Zeng, T and Bai, S and Li, S and Liu, Y and Zhong, W and Lu, C and Yang, H},
title = {Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.},
journal = {Biomaterials},
volume = {313},
number = {},
pages = {122777},
doi = {10.1016/j.biomaterials.2024.122777},
pmid = {39222545},
issn = {1878-5905},
abstract = {Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.},
}

@article {pmid39222177,
year = {2024},
author = {Kienzl, P and Deloria, AJ and Hunjadi, M and Hadolt, JM and Haering, MF and Bothien, A and Mejri, D and Korkut-Demirbaş, M and Sampl, S and Weber, G and Pirker, C and Laengle, S and Braunschmid, T and Dragona, E and Marian, B and Gagos, S and Lu, L and Henson, JD and Lau, LMS and Reddel, RR and Mikulits, W and Stättner, S and Holzmann, K},
title = {Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression.},
journal = {Cellular oncology (Dordrecht, Netherlands)},
volume = {},
number = {},
pages = {},
doi = {10.1007/s13402-024-00986-y},
pmid = {39222177},
issn = {2211-3436},
abstract = {Telomeric repeat-containing RNAs (TERRA) and telomerase RNA component (TERC) regulate telomerase activity (TA) and thereby contribute to telomere homeostasis by influencing telomere length (TL) and the cell immortality hallmark of cancer cells. Additionally, the non-canonical functions of telomerase reverse transcriptase (TERT) and TERRA appear to be involved in the epithelial-mesenchymal transition (EMT), which is important for cancer progression. However, the relationship between TERRA and patient prognosis has not been fully characterized. In this small-scale study, 68 patients with colorectal cancer (CRC) were evaluated for correlations between telomere biology, proliferation, and EMT gene transcripts and disease outcome. The proliferating cell nuclear antigen (PCNA) and the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) showed a positive correlation with TERRA, while TA and TERRA exhibited an inverse correlation. Consistent with previous findings, the present study revealed higher expression levels of TERT and TERC, and increased TA and TL in CRC tumor tissue compared to adjacent non-tumor tissue. In contrast, lower expression levels of TERRA were observed in tumor tissue. Patients with high TERRA expression and low PCNA levels exhibited favorable overall survival rates compared to individuals with the inverse pattern. Furthermore, TERRA suppressed CRC tumor growth in severe combined immunodeficiency disease (SCID) mice. In conclusion, our study extends previously published research on TERRA suggesting its potential therapeutic role in telomerase-positive CRC.},
}

@article {pmid39216403,
year = {2024},
author = {Yun, Z and Liu, Z and Shen, Y and Sun, Z and Zhao, H and Du, X and Lv, L and Zhang, Y and Hou, L},
title = {Genetic analysis from multiple cohorts implies causality between 2200 druggable genes, telomere length, and leukemia.},
journal = {Computers in biology and medicine},
volume = {181},
number = {},
pages = {109064},
doi = {10.1016/j.compbiomed.2024.109064},
pmid = {39216403},
issn = {1879-0534},
abstract = {BACKGROUND: Clinical therapeutic targets for leukemia remain to be identified and the causality between leukemia and telomere length is unclear.

METHODS: This work employed cis expression quantitative trait locus (eQTL) for 2,200 druggable genes from the eQTLGen Consortium and genome-wide association studies (GWAS) summary data for telomere length in seven blood cell types from the UK Biobank, Netherlands Cohort as exposures. GWAS data for lymphoid leukemia (LL) and myeloid leukemia (ML) from FinnGen and Lee Lab were used as outcomes for discovery and replication cohorts, respectively. Robust Mendelian randomization (MR) findings were generated from seven MR models and a series of sensitivity analyses. Summary-data-based MR (SMR) analysis and transcriptome-wide association studies (TWAS) were further implemented to verify the association between identified druggable genes and leukemia. Single-cell type expression analysis was employed to identify the specific expression of leukemia casual genes on human bone marrow and peripheral blood immune cells. Multivariable MR analysis, linkage disequilibrium score regression (LDSC), and Bayesian colocalization analysis were performed to further validate the relationship between telomere length and leukemia. Mediation analysis was used to assess the effects of identified druggable genes affecting leukemia via telomere length. Phenome-wide MR (Phe-MR) analysis for assessing the effect of leukemia causal genes and telomere length on 1,403 disease phenotypes.

RESULTS: Combining the results of the meta-analysis for MR estimates from two cohorts, SMR and TWAS analysis, we identified five LL causal genes (TYMP, DSTYK, PPIF, GDF15, FAM20A) and three ML causal genes (LY75, ADA, ABCA2) as promising drug targets for leukemia. Univariable MR analysis showed genetically predicted higher leukocyte telomere length increased the risk of LL (odds ratio [OR] = 2.33, 95 % confidence interval [95 % CI] 1.70-3.18; P = 1.33E-07), and there was no heterogeneity and horizontal pleiotropy. Evidence from the meta-analysis of two cohorts strengthened this finding (OR = 1.88, 95 % CI 1.06-3.05; P = 0.01). Multivariable MR analysis showed the causality between leukocyte telomere length and LL without interference from the other six blood cell telomere length (OR = 2.72, 95 % CI 1.88-3.93; P = 1.23E-07). Evidence from LDSC supported the positive genetic correlation between leukocyte telomere length and LL (rg = 0.309, P = 0.0001). Colocalization analysis revealed that the causality from leukocyte telomere length on LL was driven by the genetic variant rs770526 in the TERT region. The mediation analysis via two-step MR showed that the causal effect from TYMP on LL was partly mediated by leukocyte telomere length, with a mediated proportion of 12 %.

CONCLUSION: Our study identified several druggable genes associated with leukemia risk and provided new insights into the etiology and drug development of leukemia. We also found that genetically predicted higher leukocyte telomere length increased LL risk and its potential mechanism of action.},
}

@article {pmid39214240,
year = {2024},
author = {Sung, YN and Stojanova, M and Shin, S and Cho, H and Heaphy, CM and Hong, SM},
title = {Gradual Telomere Shortening in the Tumorigenesis of Pancreatic and Hepatic Mucinous Cystic Neoplasms.},
journal = {Human pathology},
volume = {},
number = {},
pages = {105653},
doi = {10.1016/j.humpath.2024.105653},
pmid = {39214240},
issn = {1532-8392},
abstract = {Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.},
}

@article {pmid39213174,
year = {2024},
author = {Martens, DS and Lammertyn, EJ and Goeminne, PC and Colpaert, K and Proesmans, M and Vanaudenaerde, BM and Nawrot, TS and Dupont, LJ},
title = {Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206093},
pmid = {39213174},
issn = {1945-4589},
abstract = {Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.},
}