Telomere length as a function of age at population level parallels human survival curves (original) (raw)
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Journal of Clinical Medicine, 2021
Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8...
Telomere Length and Mortality: A Study of Leukocytes in Elderly Danish Twins
American Journal of Epidemiology, 2008
Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL 50 ) and shortest 25% (mTRFL 25 ) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL 50 : 0.59, 95% CI: 0.52, 0.66; mTRFL 25 : 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span. by guest on December 11, 2015 http://aje.oxfordjournals.org/ Downloaded from Leukocyte Telomere Length and Mortality 801 Am J Epidemiol 2008;167:799-806 by guest on December 11, 2015 http://aje.oxfordjournals.org/ Downloaded from * MTRFL, mode of terminal restriction fragment length; mTRFL, mean terminal restriction fragment length; mTRFL 50 , lowest 50% of the terminal restriction fragment length distribution; mTRFL 25 , lowest 25% of the terminal restriction fragment length distribution.
Association between telomere length in blood and mortality in people aged 60 years or older
2003
During normal ageing, the gradual loss of telomeric DNA in dividing somatic cells can contribute to replicative senescence, apoptosis, or neoplastic transformation. In the genetic disorder dyskeratosis congenita, telomere shortening is accelerated, and patients have premature onset of many age-related diseases and early death. We aimed to assess an association between telomere length and mortality in 143 normal unrelated individuals over the age of 60 years. Those with shorter telomeres in blood DNA had poorer survival, attributable in part to a 3·18-fold higher mortality rate from heart disease (95% CI 1 . 36-7·45, p=0·0079), and an 8·54-fold higher mortality rate from infectious disease (1·52-47·9, p=0·015). These results lend support to the hypothesis that telomere shortening in human beings contributes to mortality in many age-related diseases.
Leukocyte telomere length is not associated with mortality in older men
Experimental Gerontology, 2014
Leukocyte telomere length (LTL) is related to the aging of somatic cells. We hypothesized that LTL is inversely associated with mortality in elderly men. LTL was measured in 2744 elderly men (mean age 75.5, range 69-81 years) included in the prospective population-based MrOS-Sweden study. Mortality data were obtained from national health registers with no loss of follow-up. During the follow-up (mean 6.0 years), 556 (20%) of the participants died. Using Cox proportional hazards regression, tertile of LTL did not associate with all-cause mortality [tertile 1 (shortest) or 2 (middle) vs. tertile 3 (longest); hazard ratio (HR) = 1.05, 95% confidence interval (CI) 0.85-1.28 and HR = 0.97, 95% CI 0.79-1.19, respectively]. Furthermore, LTL did not associate with cancer (197 events) or cardiovascular disease (CVD, 206 events) mortality (tertile 1 vs. tertile 3; HR = 0.94, 95% CI 0.67-1.34 and HR = 0.94, 95% CI 0.68-1.30, respectively). The lack of association between LTL and mortality remained also after adjustment for multiple covariates. Our results demonstrate that LTL is not associated with all-cause mortality or mortality due to cancer or CVD in elderly men. Further studies are needed to determine whether LTL can predict the risk of mortality in elderly women.
Epidemiology, 2015
Background: this study examined the association between leukocyte telomere length-a marker of cell aging-and mortality in a nationally representative sample of US adults ages 50-84 years. We also examined moderating effects of age, sex, race/ethnicity, and education. Methods: Data were from the national Health and nutrition examination Survey, 1999-2002 (n = 3,091). cox proportional hazards regression was used to estimate the risk of all-cause and causespecific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. Results: eight hundred and seventy deaths occurred over an average of 9.5 years of follow-up. in the full sample, a decrease of 1 kilobase pair in telomere length at baseline was marginally associated with a 10% increased hazard of all-cause mortality (hazard ratio [Hr]: 1.1, 95% confidence interval [ci]: 0.9, 1.4) and a 30% increased hazard of death due to diseases other than cardiovascular disease or cancer (Hr: 1.3, 95% ci: 0.9, 1.9). among african-american but not white or Mexican-american respondents, a decrease of 1 kilobase pair in telomere length at baseline was associated with a twofold increased hazard of cardiovascular mortality (Hr: 2.0, 95% ci: 1.3, 3.1). there was no association between telomere length and cancer mortality. Conclusions: the association between leukocyte telomere length and mortality differs by race/ethnicity and cause of death.
Leukocyte telomere dynamics in the elderly
European Journal of Epidemiology, 2013
Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants of the Longitudinal Study of Aging Danish Twins. We measured LTL by Southern blots of the terminal restriction fragment length (TRFL) in 476 individuals (73-94 years) in a cross-sectional evaluation and in a subset of this cohort comprising 80 individuals (73-81 years at baseline) who were followed-up for approximately 10 years. Based on the mean TRFL, we found that a) the average rate of LTL attrition was respectively, 27 bp/year (P \ 0.001) and 31 bp/year (P \ 0.001) for the cross-sectional and longitudinal evaluations, and b) mean TRFL was 180 bp (95 % CI 43, 320) longer in females than males (P \ 0.010). For the TRFL distribution, which captures telomeres of all lengths in the DNA sample, we observed significant shifts with age toward shorter telomeres. Based on the measurement error of the TRFLs, we computed that in the longitudinal evaluation 10.6 % of individuals would manifest LTL elongation over 10 years, assuming a 340 bp attrition during this period. This was not significantly different from the empirical observation of 7.5 % of individuals showing LTL elongation. We conclude that accumulation of ultra-short telomeres in leukocytes of the elderly reflects a shift toward shorter telomeres in the entire telomere distribution. Measurement error is the probable explanation for LTL elongation in longitudinal studies.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2009
Although telomere length (TL) is known to play a critical role in cellular senescence, the relationship of TL to aging and longevity in humans is not well understood. In a large biracial population-based cohort, we tested the hypotheses that elderly persons with shorter TL in peripheral white blood cells have poorer survival, shorter life span, and fewer years of healthy life (YHL). Associations were evaluated using Cox proportional hazard models and linear regression analyses where appropriate. TL (in kilo base pairs) was not associated with overall survival (hazard ratio 1.0; 95% confi dence interval 0.9-1.1) or death from any specifi c underlying cause including infectious diseases, cancer, or cardiac and cerebrovascular diseases. TL, however, was positively associated with more YHL (b = 0.08 ± 0.04, p = .03). Findings suggest that TL may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging.
International Journal of Epidemiology, 2014
Background: Human leukocyte telomere length (LTL) decreases with age and shorter LTL has previously been associated with increased prospective mortality. However, it is not clear whether LTL merely marks the health status of an individual by its association with parameters of immune function, for example, or whether telomere shortening also contributes causally to lifespan variation in humans. Methods: We measured LTL in 870 nonagenarian siblings (mean age 93 years), 1580 of their offspring and 725 spouses thereof (mean age 59 years) from the Leiden Longevity Study (LLS). Results: We found that shorter LTL is associated with increased prospective mortality in middle (30-80 years; hazard ratio (HR) ¼ 0.75, P ¼ 0.001) and highly advanced age
Telomere length among the elderly and oldest-old
Twin research and human genetics : the official journal of the International Society for Twin Studies, 2005
Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age...
Aging Cell, 2005
Cross-sectional studies have repeatedly suggested peripheral blood monocyte telomere length as a biomarker of aging. To test this suggestion in a large population-based follow-up study of the oldest old, we measured telomere length at baseline in 598 participants of the Leiden 85-plus Study (mean age at baseline 89.8 years). We also obtained second telomere measurements from 81 participants after an average time span of between 3.9 and 12.9 years. Telomere length at baseline was not predictive for mortality (P > 0.40 for all-cause, cardiovascular causes, cancer or infectious diseases, Cox regression for gender-adjusted tertiles of telomere length) or for the incidence of dementia (P = 0.78). Longitudinally, telomere length was highly unstable in a large fraction of participants. We conclude that blood monocyte telomere length is not a predictive indicator for age-related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomere length instability in this group.