@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.},
}

@article {pmid39208769,
year = {2024},
author = {Mlakar, V and Akkouh, I and Halff, EF and Srivastava, DP and Birkenæs, V and Ueland, T and Quintana, DS and Ormerod, MBEG and Steen, NE and Djurovic, S and Andreassen, OA and Aas, M},
title = {Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition.},
journal = {Schizophrenia research},
volume = {272},
number = {},
pages = {89-95},
doi = {10.1016/j.schres.2024.08.011},
pmid = {39208769},
issn = {1573-2509},
abstract = {OBJECTIVE: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ.

METHODS: The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively).

RESULTS: Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05).

CONCLUSION: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.},
}

@article {pmid39201686,
year = {2024},
author = {Andreikos, D and Kyrodimos, E and Kotsinas, A and Chrysovergis, A and Papacharalampous, GX},
title = {The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis.},
journal = {International journal of molecular sciences},
volume = {25},
number = {16},
pages = {},
doi = {10.3390/ijms25169000},
pmid = {39201686},
issn = {1422-0067},
mesh = {Humans ; *Head and Neck Neoplasms/genetics/pathology ; *Telomere Homeostasis ; *Telomere/genetics/metabolism ; Risk Factors ; Odds Ratio ; },
abstract = {Telomeres play a crucial role in maintaining chromosomal integrity and regulating the number of cell divisions and have been associated with cellular aging. Telomere length (TL) has been widely studied in manifold cancer types; however, the results have been inconsistent. This systematic review and meta-analysis aims to analyze the evidence on the association between TL and head and neck cancer (HNC) risk. We comprehensively searched the literature in PubMed, Cochrane Library, and Scopus and identified nine eligible studies, which yielded 11 datasets. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to ascertain the strength of the association. On the basis of the median TL, we defined two groups, short TL and long TL, with the latter being the reference group. Our analysis found a significant relationship between short TL and increased HNC risk (OR 1.38, 95% CI: 1.10-1.73, p = 0.005), while significant heterogeneity among the studies was noted. The subgroup analysis on HNC subtypes revealed a significant association between short TL and oral cancers (OR 2.08, 95% CI: 1.23-3.53, p = 0.007). Additionally, subgroup analysis indicates that adjustments for age, sex, and smoking did not affect the significance of our findings. In conclusion, our meta-analysis found evidence for an association between short TL and HNC risk, which could indicate that TL might act as a potential biomarker for HNC risk, but high-quality prospective studies are imperative to validate our findings.},
}

Humans
*Head and Neck Neoplasms/genetics/pathology
*Telomere Homeostasis
*Telomere/genetics/metabolism
Risk Factors
Odds Ratio

@article {pmid39201341,
year = {2024},
author = {Pańczyszyn, A and Boniewska-Bernacka, E and Wertel, I and Sadakierska-Chudy, A and Goc, A},
title = {Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome.},
journal = {International journal of molecular sciences},
volume = {25},
number = {16},
pages = {},
doi = {10.3390/ijms25168652},
pmid = {39201341},
issn = {1422-0067},
mesh = {Humans ; *Oxidative Stress ; *Biomarkers ; *Fertilization in Vitro/methods ; *Telomere/metabolism/genetics ; *Sirtuin 1/metabolism/genetics ; Germ Cells/metabolism ; Fertility/genetics ; Female ; Male ; },
abstract = {The number of infertile couples undergoing in vitro fertilisation (IVF) has increased significantly. The efficacy of this procedure is contingent upon a multitude of factors, including gamete quality. One factor influencing gamete quality is oxidative stress, which leads to telomere damage and accelerates cellular ageing. Identifying new biomarkers that can predict the success of assisted reproduction techniques is a current relevant area of research. In this review, we discuss the potential role of SIRT1, a protein known to protect against oxidative stress and telomeres, which are responsible for genome stability, as biomarkers of gamete quality and assisted reproduction technique outcomes.},
}

Humans
*Oxidative Stress
*Biomarkers
*Fertilization in Vitro/methods
*Telomere/metabolism/genetics
*Sirtuin 1/metabolism/genetics
Germ Cells/metabolism
Fertility/genetics
Female
Male

@article {pmid39200358,
year = {2024},
author = {Khalatyan, AS and Shishparenok, AN and Avetisov, KS and Gladilina, YA and Blinova, VG and Zhdanov, DD},
title = {Association of Telomere Length in T Lymphocytes, B Lymphocytes, NK Cells and Monocytes with Different Forms of Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {8},
pages = {},
doi = {10.3390/biomedicines12081893},
pmid = {39200358},
issn = {2227-9059},
abstract = {BACKGROUND: Age plays a primary role in the development of age-related macular degeneration (AMD). Telomere length (TL) is one of the most relevant biomarkers of aging. In our study, we aimed to determine the association of TL with T lymphocytes, B lymphocytes, NK cells or monocytes with different forms of AMD.

METHODS: Our study included 62 patients with AMD: geographic atrophy (GA), neovascular AMD (NVAMD) with and without macular atrophy and 22 healthy controls. Each leukocyte subtype was isolated from peripheral blood by immunomagnetic separation, and the DNA was purified. The TL in the genomic DNA was determined using qPCR by amplifying the telomere region with specific oligonucleotide primers and normalizing to the control gene. Statistical analysis was performed using R version 4.5.1.

RESULTS: We observed a statistically significant increase in TL in the T cells between the control and NVAMD groups but not for the GA group. The B cells and monocytes showed a significant decrease in TL in all AMD groups. The TL in the NK cells did not decrease in any of the AMD groups.

CONCLUSIONS: The TL in the monocytes had the strongest association with AMD. It reflects a person's "telomeric status" and may become a diagnostic hallmark of these degenerative processes.},
}

@article {pmid39200189,
year = {2024},
author = {Levstek, T and Breznik, N and Vujkovac, B and Nowak, A and Trebušak Podkrajšek, K},
title = {Dynamics of Leukocyte Telomere Length in Patients with Fabry Disease.},
journal = {Biomedicines},
volume = {12},
number = {8},
pages = {},
doi = {10.3390/biomedicines12081724},
pmid = {39200189},
issn = {2227-9059},
support = {P1-0170//Slovenian Research Agency/ ; NA//Takeda Pharmaceuticals/ ; },
abstract = {Fabry disease (FD) leads to significant morbidity and mortality, which may indicate accelerated ageing. However, it is still unclear whether there is a relationship between telomere length (TL), a marker of biological ageing, and disease outcome. We aimed to examine the relationship between leukocyte TL (LTL) dynamics and the presence of advanced disease stages and/or late complications of FD, including hypertrophic cardiomyopathy, nephropathy and stroke, both cross-sectionally and longitudinally. DNA was extracted from peripheral blood leukocytes and quantitative PCR was utilized to determine relative LTL in 99 Fabry patients. In the longitudinal analysis, we included 50 patients in whom at least three measurements were performed over a period of 5-10 years. The results showed a significant inverse correlation between LTL and age (ρ = -0.20, p = 0.05). No significant differences in LTL were found between females and males (p = 0.79) or between patients receiving disease-specific therapy and those without (p = 0.34). In a cross-sectional analysis, no association was found between the presence (p = 0.15) or number (p = 0.28) of advanced stages of the disease and/or late complications and LTL. Similarly, in a longitudinal analysis, no difference in LTL dynamics was found regarding the presence (p = 0.16) of advanced stage organ involvement and/or late complications or their number. These findings indicate that LTL dynamics in adulthood may not be a reliable indicator of disease outcomes in Fabry patients. Therefore, LTL may more accurately reflect the disease burden in early life, when TL is primarily determined.},
}

@article {pmid39198715,
year = {2024},
author = {Tummala, H and Walne, AJ and Badat, M and Patel, M and Walne, AM and Alnajar, J and Chow, CC and Albursan, I and Frost, JM and Ballard, D and Killick, S and Szitányi, P and Kelly, AM and Raghavan, M and Powell, C and Raymakers, R and Todd, T and Mantadakis, E and Polychronopoulou, S and Pontikos, N and Liao, T and Madapura, P and Hossain, U and Vulliamy, T and Dokal, I},
title = {The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39198715},
issn = {1757-4684},
support = {MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; 14032/LLR_/Blood Cancer UK/United Kingdom ; 14032/LLR_/Blood Cancer UK/United Kingdom ; },
abstract = {Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders.},
}

@article {pmid39198664,
year = {2024},
author = {Qiu, YD and Yan, Q and Wang, Y and Ye, YF and Wang, Y and Wang, MY and Wang, PP and Zhang, SY and Wang, DL and Yan, H and Ruan, J and Zhao, YJ and Huang, LH and Cho, N and Wang, K and Zheng, XH and Liu, ZG},
title = {Author Correction: Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41401-024-01370-0},
pmid = {39198664},
issn = {1745-7254},
}

@article {pmid39197728,
year = {2024},
author = {Neto, IVS and Pinto, AP and de Andrade, RV and de Souza, FHV and de Souza, PEN and Assis, V and Tibana, RA and Neves, RVP and Rosa, TDS and Prestes, J and da Silva, ASR and Marqueti, RC},
title = {Paternal exercise induces antioxidant defenses by α-Klotho/Keap1 pathways in the skeletal muscle of offspring exposed to a high fat-diet without changing telomere length.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {109747},
doi = {10.1016/j.jnutbio.2024.109747},
pmid = {39197728},
issn = {1873-4847},
abstract = {Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Pre-conceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (Keap1) mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise.},
}

@article {pmid39197110,
year = {2024},
author = {Roka, K and Solomou, E and Kattamis, A and Stiakaki, E},
title = {Telomere biology disorders: from dyskeratosis congenita and beyond.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgae102},
pmid = {39197110},
issn = {1469-0756},
abstract = {Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.},
}

@article {pmid39195250,
year = {2024},
author = {Ghilain, C and Vidal-Cruchez, O and Joly, A and Debatisse, M and Gilson, E and Giraud-Panis, MJ},
title = {Innovative Tools for DNA Topology Probing in Human Cells Reveal a Build-Up of Positive Supercoils Following Replication Stress at Telomeres and at the FRA3B Fragile Site.},
journal = {Cells},
volume = {13},
number = {16},
pages = {},
doi = {10.3390/cells13161361},
pmid = {39195250},
issn = {2073-4409},
support = {TELOCHROM//Agence Nationale de la Recherche/ ; REPLITOP//French National Cancer Institute/ ; Equipe labellisée//Fondation ARC pour la Recherche sur le Cancer/ ; },
mesh = {Humans ; *Telomere/metabolism ; *DNA, Superhelical/metabolism ; *DNA Replication ; Chromosome Fragile Sites ; Telomeric Repeat Binding Protein 2/metabolism/genetics ; Nucleic Acid Conformation ; DNA/metabolism ; DNA Topoisomerases, Type II/metabolism ; },
abstract = {Linear unconstrained DNA cannot harbor supercoils since these supercoils can diffuse and be eliminated by free rotation of the DNA strands at the end of the molecule. Mammalian telomeres, despite constituting the ends of linear chromosomes, can hold supercoils and be subjected to topological stress. While negative supercoiling was previously observed, thus proving the existence of telomeric topological constraints, positive supercoils were never probed due to the lack of an appropriate tool. Indeed, the few tools available currently could only investigate unwound (Trioxsalen) or overwound (GapR) DNA topology (variations in twist) but not the variations in writhe (supercoils and plectonemes). To address this question, we have designed innovative tools aimed at analyzing both positive and negative DNA writhe in cells. Using them, we could observe the build-up of positive supercoils following replication stress and inhibition of Topoisomerase 2 on telomeres. TRF2 depletion caused both telomere relaxation and an increase in positive supercoils while the inhibition of Histone Deacetylase I and II by TSA only caused telomere relaxation. Moving outside telomeres, we also observed a build-up of positive supercoils on the FRA3B fragile site following replication stress, suggesting a topological model of DNA fragility for this site.},
}

Humans
*Telomere/metabolism
*DNA, Superhelical/metabolism
*DNA Replication
Chromosome Fragile Sites
Telomeric Repeat Binding Protein 2/metabolism/genetics
Nucleic Acid Conformation
DNA/metabolism
DNA Topoisomerases, Type II/metabolism

@article {pmid39192622,
year = {2024},
author = {Aali, R and Asli Gharehbagh, H and Gholampour, A and Sorooshian, A and Panahi, Y},
title = {Children exposed to salt-dust emission from Urmia Lake have short telomere length: a case-control pilot study.},
journal = {International journal of environmental health research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/09603123.2024.2394136},
pmid = {39192622},
issn = {1369-1619},
abstract = {This study aimed to measure telomere length in healthy children living next to Urmia Lake, Iran, which is exposed to salt dust from a drying lakebed. In this case-control pilot study, we recruited 39 sex- and age-matched healthy children from two different geographic regions to study the relative telomere lengths using qPCR. We categorized the study samples into high-impact and low-impact areas based on wind direction, aerosol particle level, and distance from the lake. Our main results revealed that children living in high-impact areas have shorter telomeres than those living in low-impact areas. Furthermore, according to our statistical model, parental age significantly affected telomere length in children, but inversely. When the father's age impact was positive, the mother had a negative effect. Based on our results, to prevent Urmia Lake from dying out completely, national and international organizations should implement comprehensive visions and strategies for its restoration.},
}

@article {pmid39192284,
year = {2024},
author = {Zhuang, X and Chen, P and Yang, R and Man, X and Wang, R and Shi, Y},
title = {Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {120},
pmid = {39192284},
issn = {1868-7083},
support = {Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; No. LQ19H080002//Natural Science Foundation of Zhejiang Province/ ; },
abstract = {BACKGROUND: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks.

METHODS: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR).

RESULTS: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, PIVW = 0.034), MCH (OR = 0.801, PIVW = 2.046e-06), MCV (OR = 0.801, PIVW = 0.001), and MCHC (OR = 0.813, PIVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, PIVW = 0.007).

CONCLUSION: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.},
}

@article {pmid39192095,
year = {2024},
author = {Burren, OS and Dhindsa, RS and Deevi, SVV and Wen, S and Nag, A and Mitchell, J and Hu, F and Loesch, DP and Smith, KR and Razdan, N and Olsson, H and Platt, A and Vitsios, D and Wu, Q and , and Codd, V and Nelson, CP and Samani, NJ and March, RE and Wasilewski, S and Carss, K and Fabre, M and Wang, Q and Pangalos, MN and Petrovski, S},
title = {Genetic architecture of telomere length in 462,666 UK Biobank whole-genome sequences.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39192095},
issn = {1546-1718},
support = {MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; MR/M012816/1//British Heart Foundation (BHF)/ ; },
abstract = {Telomeres protect chromosome ends from damage and their length is linked with human disease and aging. We developed a joint telomere length metric, combining quantitative PCR and whole-genome sequencing measurements from 462,666 UK Biobank participants. This metric increased SNP heritability, suggesting that it better captures genetic regulation of telomere length. Exome-wide rare-variant and gene-level collapsing association studies identified 64 variants and 30 genes significantly associated with telomere length, including allelic series in ACD and RTEL1. Notably, 16% of these genes are known drivers of clonal hematopoiesis-an age-related somatic mosaicism associated with myeloid cancers and several nonmalignant diseases. Somatic variant analyses revealed gene-specific associations with telomere length, including lengthened telomeres in individuals with large SRSF2-mutant clones, compared with shortened telomeres in individuals with clonal expansions driven by other genes. Collectively, our findings demonstrate the impact of rare variants on telomere length, with larger effects observed among genes also associated with clonal hematopoiesis.},
}

@article {pmid39190187,
year = {2024},
author = {Milosevic, T and Naumovic, R and Sopic, M and Vekic, J and Guzonjic, A and Pesic, S and Miljkovic-Trailovic, M and Kotur-Stevuljevic, J},
title = {COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {938},
pmid = {39190187},
issn = {1573-4978},
support = {451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; },
mesh = {Humans ; *COVID-19/mortality/virology ; Male ; Female ; *Renal Dialysis ; Middle Aged ; Aged ; *C-Reactive Protein/metabolism ; *Inflammation ; Lymphocytes/metabolism ; Neutrophils/metabolism ; Telomere/genetics/metabolism ; SARS-CoV-2 ; L-Lactate Dehydrogenase/blood ; Kaplan-Meier Estimate ; Kidney Failure, Chronic/therapy/mortality/blood ; },
abstract = {BACKGROUND AND OBJECTIVE: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL).

MATERIALS AND METHODS: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis.

RESULTS: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient's survival in this group of parameters (log rank 25.4, p < 0.001).

CONCLUSION: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients.},
}

Humans
*COVID-19/mortality/virology
Male
Female
*Renal Dialysis
Middle Aged
Aged
*C-Reactive Protein/metabolism
*Inflammation
Lymphocytes/metabolism
Neutrophils/metabolism
Telomere/genetics/metabolism
SARS-CoV-2
L-Lactate Dehydrogenase/blood
Kaplan-Meier Estimate
Kidney Failure, Chronic/therapy/mortality/blood

@article {pmid39189448,
year = {2024},
author = {Wondimagegnhu, B and Ma, W and Paul, T and Liao, TW and Lee, CY and Sanford, S and Opresko, PL and Myong, S},
title = {The molecular mechanism for TERRA recruitment and annealing to telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae732},
pmid = {39189448},
issn = {1362-4962},
support = {F31CA268939/GF/NIH HHS/United States ; },
abstract = {Telomeric repeat containing RNA (TERRA) is a noncoding RNA that is transcribed from telomeres. Previous study showed that TERRA trans anneals by invading into the telomeric duplex to form an R-loop in mammalian cells. Here, we elucidate the molecular mechanism underlying TERRA recruitment and invasion into telomeres in the context of shelterin proteins, RAD51 and RNase H using single molecule (sm) assays. We demonstrate that TERRA trans annealing into telomeric DNA exhibits dynamic movement that is stabilized by TRF2. TERRA annealing to the telomeric duplex results in the formation of a stable triplex structure which differs from a conventional R-loop. We identified that the presence of a sub-telomeric DNA and a telomeric overhang in the form of a G-quadruplex significantly enhances TERRA annealing to telomeric duplex. We also demonstrate that RAD51-TERRA complex invades telomere duplex more efficiently than TERRA alone. Additionally, TRF2 increases TERRA affinity to telomeric duplex and protects it from RNase H digestion. In contrast, TRF1 represses TERRA annealing to telomeric duplex and fails to provide protection against RNase H digestion. Our findings provide an in-depth molecular mechanism underpinning TERRA recruitment and annealing to the telomere.},
}

@article {pmid39188883,
year = {2024},
author = {Murillo-Ortiz, BO and García-Corrales, K and Martínez-Garza, S and Romero-Vázquez, MJ and Agustín-Godínez, E and Escareño-Gómez, A and Silva-Guerrero, DG and Mendoza-Ramírez, S and Murguia-Perez, M},
title = {Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1450147},
pmid = {39188883},
issn = {2296-858X},
abstract = {BACKGROUND: Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters.

MATERIALS AND METHODS: A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT.

RESULTS: Of the 21 cases included in the study, the median age was 57.57 years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p = 0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p = 0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14 ± 1.54 vs. 4.75 ± 1.96 Kb, p = 0.007).

CONCLUSION: Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.},
}

@article {pmid39188229,
year = {2024},
author = {Kim, D and Danpanichkul, P and Wijarnpreecha, K and Cholankeril, G and Ahmed, A},
title = {Leukocyte Telomere Shortening in MASLD and All-cause/Cause-specific Mortality.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2024.0691},
pmid = {39188229},
issn = {2287-285X},
}

@article {pmid39180127,
year = {2024},
author = {Song, Y and Xu, J and Geng, W and Yin, L and Wang, J and Zhao, J},
title = {Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis.},
journal = {Orphanet journal of rare diseases},
volume = {19},
number = {1},
pages = {309},
pmid = {39180127},
issn = {1750-1172},
support = {no. 19-1124-038//Shenyang Science and Technology Bureau, China/ ; },
mesh = {Humans ; *Telomerase/genetics ; *Mendelian Randomization Analysis ; *Cerebral Small Vessel Diseases/genetics ; *Polymorphism, Single Nucleotide/genetics ; Female ; *Leukocytes/metabolism ; Male ; Middle Aged ; Asian People/genetics ; Aged ; Telomere/genetics ; Genetic Predisposition to Disease ; Genotype ; China ; Risk Factors ; East Asian People ; },
abstract = {BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD.

METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk.

RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk.

CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.},
}

Humans
*Telomerase/genetics
*Mendelian Randomization Analysis
*Cerebral Small Vessel Diseases/genetics
*Polymorphism, Single Nucleotide/genetics
Female
*Leukocytes/metabolism
Male
Middle Aged
Asian People/genetics
Aged
Telomere/genetics
Genetic Predisposition to Disease
Genotype
China
Risk Factors
East Asian People

@article {pmid39179728,
year = {2024},
author = {Jin, Z and Liu, X and Guo, H and Chen, S and Zhu, X and Pan, S and Wu, Y},
title = {Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.},
journal = {Journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {39179728},
issn = {1573-3521},
support = {81971019//National Natural Science Foundation of China/ ; 82271482//National Natural Science Foundation of China/ ; },
abstract = {Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (β = - 0.037, 95% CI = - 0.070, - 0.005), while CRP was associated with telomere length in males only (β = - 0.019, 95% CI = - 0.035, - 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role.},
}

@article {pmid39178054,
year = {2024},
author = {Squassina, A and Pisanu, C and Menesello, V and Meloni, A and Congiu, D and Manchia, M and Paribello, P and Abate, M and Bortolomasi, M and Baune, BT and Gennarelli, M and Minelli, A},
title = {Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Treatment-Resistant Depression and Response to Electroconvulsive Therapy: A Pilot Longitudinal Study.},
journal = {The journal of ECT},
volume = {},
number = {},
pages = {},
doi = {10.1097/YCT.0000000000001060},
pmid = {39178054},
issn = {1533-4112},
abstract = {OBJECTIVES: In this study, we investigated if changes in leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-cn), 2 markers of cellular aging, are associated with treatment-resistant depression (TRD) and with response to electroconvulsive therapy (ECT).

METHODS: LTL and mtDNA-cn were measured in 31 TRD patients before (T0), 1 week (T1), and 4 weeks (T2) after the ECT course, as well as in a sample of 65 healthy controls.

RESULTS: TRD patients had significantly shorter LTL and higher mtDNA-cn compared with healthy controls at baseline. In the TRD sample, LTL was inversely correlated with Montgomery-Åsberg Depression Rating Scale scores at baseline. Baseline levels of LTL or mtDNA-cn were not correlated with response to ECT. Similarly, changes in LTL or mtDNA-cn were not associated with response to ECT either when considered as a dichotomous trait (responders vs nonresponders) or as a percentage change in symptoms improvements.

CONCLUSIONS: Ours is the first longitudinal study exploring the role of LTL and mtDNA-cn in response to ECT. Findings of this pilot investigation suggest that LTL and mtDNA-cn may constitute disease biomarkers for TRD but are not involved in response to ECT.},
}

@article {pmid39177475,
year = {2024},
author = {He, Z and Wu, J and Li, W and Du, Y and Lu, L},
title = {Investigation of G-Quadruplex DNA-Mediated Charge Transport for Exploring DNA Oxidative Damage in Telomeres.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.langmuir.4c01604},
pmid = {39177475},
issn = {1520-5827},
abstract = {The human telomeric DNA 3' single-stranded overhang comprises tandem repeats of the sequence d(TTAGGG), which can fold into the stable secondary structure G-quadruplex (G4) and is susceptible to oxidative damage due to the enrichment of G bases. 8-Oxoguanine (8-oxoG) formed in telomeric DNA destabilizes G4 secondary structures and then inhibits telomere functions such as the binding of G4 proteins and the regulation of the length of telomeres. In this work, we developed a G4-DNA self-assembled monolayer electrochemical sensing interface using copper-free click chemistry based on the reaction of dibenzocyclooctyl with azide, resulting in a high yield of DNA tethers with order and homogeneity surfaces, that is more suitable for G-quadruplex DNA charge transport (CT) research. At high DNA coverage density surfaces, G-quadruplex DNA is 4 times more conductive than double-stranded DNA owing to the well-stacked aromatic rings of G-quartets acting as good charge transfer channels. The effect of telomeric oxidative damage on G-quadruplex-mediated CT is investigated. The accommodation of 8-oxoG at G sites originally in the syn or anti conformation around the glycosyl bond in the nonsubstituted hTel G-quadruplex causes structural perturbation and a conformational shift, which disrupts the π-stack, affecting the charge transfer and attenuating the electrochemical signal. The current intensity was found to correlate with the amount of 8-oxodG, and the detection limit was estimated to be approximately one lesion in 286 DNA bases, which can be converted into 64.7 fmol on the basis of the total surface DNA coverage. The improved G4-DNA order and homogeneity sensing interface represent a major step forward in this regard, providing a reliable and controlled electrochemical platform for the accurate measurement and diagnosis of G4-DNA oxidative damage.},
}

@article {pmid39173315,
year = {2024},
author = {Vaz, D and Vasconcelos, S and Caniçais, C and Costa, B and Ramalho, C and Marques, J and Dória, S},
title = {X-chromosome inactivation pattern and telomere length in recurrent pregnancy loss.},
journal = {Reproductive biology},
volume = {24},
number = {4},
pages = {100933},
doi = {10.1016/j.repbio.2024.100933},
pmid = {39173315},
issn = {2300-732X},
abstract = {Recurrent pregnancy loss is a reproductive disorder affecting about 1 to 5 % of pregnant women worldwide that requires our attention, especially considering that about 50 % of cases are idiopathic. The present study is focused on testing a possible association between extreme skewed X-chromosome inactivation patterns and/or shortened telomeres with idiopathic cases since both are considered non-consensual potential causes underlying recurrent pregnancy loss in the scientific community. For this purpose, two groups of women were analyzed and compared: a group of women with idiopathic recurrent pregnancy loss and a second group of age-matched women with proven fertility, and both X-chromosome inactivation patterns and telomere length were measured and compared from maternal DNA extracted from peripheral blood. Our data showed no statistically significant differences between groups, suggesting no association between extreme skewed X-chromosome inactivation or shortened telomeres with recurrent pregnancy losses. Additionally, the effect of maternal age on both X-chromosome inactivation pattern and telomere length was tested, but no significant correlation was observed between advanced maternal age and extreme skewed X-chromosome inactivation or telomere shortening. This study represents one more valid contribution to the investigation of causes underlying recurrent pregnancy loss suggesting that, new variables may be considered since the pattern of X-chromosome inactivation and telomere length do not seem to be related to this reproductive disorder. Briefly, considering its clinical relevance, it is mandatory a continuous effort in the scientific community to cover new potential recurrent pregnancy loss-related causes.},
}

@article {pmid39174689,
year = {2024},
author = {Spinou, M and Naska, A and Nelson, CP and Codd, V and Samani, NJ and Bountziouka, V},
title = {Micronutrient intake and telomere length: findings from the UK Biobank.},
journal = {European journal of nutrition},
volume = {},
number = {},
pages = {},
pmid = {39174689},
issn = {1436-6215},
support = {MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {PURPOSE: To investigate whether micronutrient intake from food as well as the regular uptake of specific vitamins and/or minerals are associated with leucocyte telomere length (LTL).

METHODS: This is a cross-sectional study using data from 422,693 UK Biobank participants aged from 40 to 69 years old, during 2006-2010. LTL was measured as the ratio of telomere repeat number to a single-copy gene and was loge-transformed and z-standardized (z-LTL). Information concerning supplement use was collected at baseline through the touchscreen assessment, while micronutrient intake from food were self-reported through multiple web-based 24 h recall diaries. The association between micronutrient intake or supplement use and z-LTL was assessed using multivariable linear regression models adjusting for demographic, lifestyle and clinical characteristics.

RESULTS: About 50% (n = 131,810) of the participants, with complete data on all covariates, self-reported regular supplement intake. Whilst overall supplement intake was not associated with z-LTL, trends toward shorter z-LTL with regular vitamin B (-0.019 (95% CI: -0.041; 0.002)) and vitamin B9 (-0.027 (-0.054; 0.000)) supplement intake were observed. z-LTL was associated with food intake of pantothenic acid (-0.020 (-0.033; -0.007)), vitamin B6 (-0.015 (-0.027; -0.003)), biotin (0.010 (0.002; 0.018)) and folate (0.016 (0.003; 0.030)). Associations of z-LTL with these micronutrients were differentiated according to supplement intake.

CONCLUSION: Negative associations equivalent to a year or less of age-related change in LTL between micronutrient intake and LTL were observed. Due to this small effect, the clinical importance of the associations and any relevance to the effects of vitamin and micronutrient intake toward chronic disease prevention remains uncertain.},
}

@article {pmid39170634,
year = {2024},
author = {Domínguez-de-Barros, A and Sifaoui, I and Dorta-Guerra, R and Lorenzo-Morales, J and Castro-Fuentes, R and Córdoba-Lanús, E},
title = {DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity.},
journal = {Frontiers in veterinary science},
volume = {11},
number = {},
pages = {1430861},
pmid = {39170634},
issn = {2297-1769},
abstract = {Aging is a complex process influenced by internal and external factors. Oxidative stress damages DNA, leading to 8-hydroxy-2' deoxyguanosine formation (8-OHdG). Telomere shortening is considered a biomarker of aging and oxidative stress may enhance its attrition. The ability to manage and repair oxidative stress varies among species and life histories. Avian species, such as Psittacidae birds, exhibit exceptional lifespans despite their physiological characteristics that might suggest otherwise. This study investigates 8-OHdG levels in serum samples from long- and short-lived birds of the order Psittaciformes, examining their relationship with telomere length and antioxidant capacity based on lifespan strategies. Among 43 individuals analyzed 26 belonged to the "long-lived species" group and 17 belonged to the "short-lived species" one. Relative telomere length (rTL) was measured in DNA isolated from whole blood by qPCR, and oxidative stress markers, such as Total Antioxidant Capacity (TAC) and 8-OHdG, were determined by spectrophotometry in serum samples. Long-lived birds had longer rTL than short-lived ones [1.308 ± 0.11 vs. 0.565 ± 0.13, (p < 0.001)]. On the contrary, short-lived birds showed more DNA damage than their counterparts [3.847 ± 0.351 vs. 2.012 ± 0.308, respectively, (p < 0.001)]. Old birds had shorter rTL than young ones, for both longevity groups (p < 0.001). Although no correlation was found between 8-OHdG levels and age, nor 8-OHdG and telomere length, long-lived birds exhibited 75.42-unit increased TAC levels when increased 8-OHdG concentrations (p = 0.046). These findings highlight distinct patterns of telomere length and oxidative stress influenced by lifespan strategies among avian longevity groups.},
}

@article {pmid39164231,
year = {2024},
author = {Ghosh, S and Nguyen, MT and Choi, HE and Stahl, M and Kühn, AL and Van der Auwera, S and Grabe, HJ and Völzke, H and Homuth, G and Myers, SA and Hogaboam, CM and Noth, I and Martinez, FJ and Petsko, GA and Glimcher, LH},
title = {RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {7138},
pmid = {39164231},
issn = {2041-1723},
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/genetics/metabolism/pathology ; *Telomere Shortening ; *Telomerase/metabolism/genetics ; *Nuclear Proteins/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; Fibroblasts/metabolism ; Myelodysplastic Syndromes/genetics/metabolism ; Telomere/metabolism/genetics ; Gene Expression Regulation ; Lung/metabolism/pathology ; },
abstract = {Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.},
}

Humans
*Idiopathic Pulmonary Fibrosis/genetics/metabolism/pathology
*Telomere Shortening
*Telomerase/metabolism/genetics
*Nuclear Proteins/metabolism/genetics
*Cell Cycle Proteins/metabolism/genetics
Fibroblasts/metabolism
Myelodysplastic Syndromes/genetics/metabolism
Telomere/metabolism/genetics
Gene Expression Regulation
Lung/metabolism/pathology

@article {pmid39159130,
year = {2024},
author = {Maimaiti, A and Ma, J and Hao, C and Han, D and Wang, Y and Wang, Z and Abudusalamu, R},
title = {DNA methylation-estimated phenotypes, telomere length and risk of ischemic stroke: epigenetic age acceleration of screening and a Mendelian randomization study.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206072},
pmid = {39159130},
issn = {1945-4589},
abstract = {BACKGROUND: Aging is a complex biological process that may be accelerated in certain pathological conditions. DNA methylation age (DNAmAge) has emerged as a biomarker for biological age, which can differ from chronological age. This research peels back the layers of the relationship between fast-forward aging and ischemic stroke, poking and prodding the potential two-way causal influences between stroke and biological aging indicators.

METHODS: We analyzed a cohort of ischemic stroke patients, comparing DNAmAge with chronological age to measure age acceleration. We assessed variations in age acceleration among stroke subtypes and between sexes. Using Mendelian randomization, we examined the causal links between stroke, aging biomarkers like telomere length, and age acceleration's effect on stroke risk.

RESULTS: Our investigation reveals a pronounced association between ischemic stroke and age acceleration, most notably in patients with cardioembolic strokes, who exhibited a striking median difference of 9 years between DNAmAge and chronological age. Furthermore, age acceleration differed significantly across stroke subtypes and was higher in women than in men. In terms of causality, MR analysis indicated a modest negative effect of stroke on telomere length, but no causal effect of age phenotypes on stroke or its subtypes. However, some indication of a potential causal effect of ischemic stroke on PhenoAge acceleration was observed.

CONCLUSION: The study provides insight into the relationship between DNAmAge and ischemic stroke, particularly cardioembolic stroke, and suggests possible gender differences. These insights carry profound clinical significance and set stage for future investigations into the entwined pathways of stroke and accelerated aging.},
}