Association of leukocyte telomere length and the risk of age-related hearing impairment in Chinese Hans.
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ABSTRACT:
SUBMITTER: Liu H
PROVIDER: S-EPMC5578975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionWith advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length.MethodsThe study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).ResultsIn the older people there was a higher wall thickness than in the younger (1.03 ± 0.09 vs. 0.88 ± 0.10, p<0.01), whereas LV mass index was comparable between them (85.8 ± 15.40 vs. 83.1 ± 11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (β = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV.ConclusionsOur data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.
| S-EPMC4537122 | biostudies-literature
Project description:BACKGROUND:Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. METHODS:We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women ?65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. RESULTS:For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). CONCLUSIONS:Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause.
| S-EPMC3926311 | biostudies-literature
Project description:BackgroundAge-related hearing impairment (ARHI) has attracted increasing attention recently. It is caused by genetic and environmental factors. A number of ARHI-related genes have been found. This study aimed to detect the potential association between NR3C1 gene polymorphisms and ARHI by means of weighted allele score.MethodsA total of 861 participants from Qingdao city were selected by means of cluster random sampling. We statistically evaluated the characteristics of individuals and used the Mann-Whitney U test or chi-square test for comparison. The publicly available expression quantitative trait locus (eQTL) was queried on the website of the Genotype-Tissue Expression (GTEx). We used the weighted allele score and logistic regression analysis to explore the association between NR3C1 gene polymorphisms and ARHI. Finally, the prediction model was constructed by logistic regression and receiver operating characteristic (ROC) curve.ResultsAll individuals over 60 years of age were enrolled in this study. The allele of rs61757411, rs41423247 and rs6877893 were significantly different between the ARHI group and the normal hearing group (P < 0.01). Though eQTL analysis, rs6877893 and rs33388 might affect the occurrence of ARHI by affecting the expression of NR3C1 gene in artery aorta. Then we performed two models: one without adding any covariates into model and the other adjusting for demographic characteristic, smoking and drinking, diet and exercise, and physical conditions. In the multivariate-adjusted model 2, the odds ratio with 95% confidence interval for weighted allele score (NR3C1) was 0.841 (0.710-0.995, P = 0.043). The area under the ROC curve was 0.755, indicating that the model had good predictability.ConclusionsOur study suggests that NR3C1 gene polymorphisms was significantly associated with ARHI.
| S-EPMC8320226 | biostudies-literature
Project description:Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.
| S-EPMC2242810 | biostudies-literature
Project description:Telomere length is associated with age-related diseases and is highly heritable. It is unclear, however, to what extent epigenetic modifications are associated with leukocyte telomere length (LTL). In this study, we conducted a large-scale epigenome-wide association study (EWAS) of LTL using seven large cohorts (n=5,713) - the Framingham Heart Study, the Jackson Heart Study, the Women's Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins. Our stratified analysis suggests that EWAS findings for women of African ancestry may be distinct from those of three other groups: males of African ancestry, and males and females of European ancestry. Using a meta-analysis framework, we identified DNA methylation (DNAm) levels at 823 CpG sites to be significantly associated (P<1E-7) with LTL after adjusting for age, sex, ethnicity, and imputed white blood cell counts. Functional enrichment analyses revealed that these CpG sites are near genes that play a role in circadian rhythm, blood coagulation, and wound healing. Weighted correlation network analysis identified four co-methylation modules associated with LTL, age, and blood cell counts. Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes.
| S-EPMC6738430 | biostudies-literature
Project description:Telomere shortening is well known to be associated with ageing. Age is the most decisive risk factor for age-related macular degeneration (AMD) development. The older the individual, the higher the AMD risk. For this reason, we aimed to find any associations between telomere length, distribution of genetic variants in telomere-related genes (TERT, TERT-CLPTM1, TRF1, TRF2, and TNKS2), and serum TERF-1 and TERF2 levels on AMD development.MethodsOur study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA).ResultsWe found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group.ConclusionsIn conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.
| S-EPMC9740443 | biostudies-literature
Project description:BackgroundAlthough telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States.MethodsA total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999-2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels.ResultsThe mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted β-21.45, 95% CI -37.28, -5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted β0.18, 95% CI -2.21, 2.57; P = 0.8809).ConclusionOur findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.
| S-EPMC9204082 | biostudies-literature
Project description:BackgroundTelomeres and telomerase play key roles in the chromosomal maintenance and stability. Recent epidemiological studies have shown that longer telomeres are associated with increased risk of several cancer types. However, epidemiological data for telomere length and risk of breast cancer are sparse.MethodsWe prospectively studied the association between telomere length and risk of breast cancer in 14,305 middle-aged or older Chinese women of the Singapore Chinese Health Study including 442 incident breast cancer cases after 12.3 years of follow-up. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiple quantitative polymerase chain reaction method. The Cox proportional hazard regression method was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for breast cancer associated with longer telomeres after adjustment for potential confounders.ResultsLonger telomeres were significantly associated with higher risk of breast cancer in a dose-dependent manner (Ptrend = 0.006); the highest quartile of telomere length was associated with a statistically significant 47% higher risk of breast cancer compared with the lowest quartile of telomere length after the adjustment for age and other known risk factors for breast cancer (HRQ4 vs Q1 = 1.47, 95% CI = 1.11, 1.94).ConclusionsThe findings of the present study support the hypothesis that longer telomeres may be a risk factor for breast cancer. Telomere length in peripheral blood leukocytes may be developed as a biomarker for breast cancer risk prediction.
| S-EPMC6471852 | biostudies-literature
Project description:Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age? the extrinsic epigenetic age acceleration (EEAA)? is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826). EEAA was computed using 71 DNA methylation sites, further weighted by proportions of naïve CD8+ T cells, memory CD8+ T cells, and plasmablasts. Shorter LTL was associated with increased EEAA in participants from the WHI (r=-0.16, p=3.1x10-6). This finding was replicated in the FHS (r=-0.09, p=6.5x10-3) and the BHS (r=-0.07, p=3.8x 10-2). LTL was also inversely related to proportions of memory CD8+ T cells (p=4.04x10-16) and positively related to proportions of naive CD8+ T cells (p=3.57x10-14). These findings suggest that for a given age, an individual whose blood contains comparatively more memory CD8+ T cells and less naive CD8+ T cells would display a relatively shorter LTL and an older DNA methylation age, which jointly explain the striking ability of EEAA to predict mortality.
| S-EPMC5636670 | biostudies-literature
Project description:BackgroundInter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases.ResultIn this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity.ConclusionsThese findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19.Supplementary informationThe online version contains supplementary material available at 10.1186/s43042-023-00415-z.
| S-EPMC10225776 | biostudies-literature