Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study (original) (raw)
Related papers
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.
Telomere Length in Elderly Caucasians Weakly Correlates with Blood Cell Counts
The Scientific World Journal, 2013
Background. Age-related decrease in bone marrow erythropoietic capacity is often accompanied by the telomere length shortening in peripheral white blood cells. However, limited and conflicting data hamper the conclusive opinion regarding this relationship. Therefore, the aim of this study was to assess an association between telomere length and peripheral blood cell count parameters in the Polish elderly population. Material and Methods. The substudy included 1573 of 4981 subjects aged 65 years or over, participants of the population-based PolSenior study. High-molecular-weight DNA was isolated from blood mononuclear cells. Telomere length (TL) was measured by QRT-PCR as abundance of telomere template versus a single gene copy encoding acidic ribosomal phosphoprotein P0. Results. Only white blood count (WBC) was significantly different in TL tertile subgroups in all subjects ( = 0.02) and in men ( = 0.01), but not in women. Merely in men significant but weak positive correlations were found between TL and WBC ( = 0.11, < 0.05) and RBC ( = 0.08, < 0.05). The multiple regression analysis models confirmed a weak, independent contribution of TL to both RBC and WBC. Conclusions. In the elderly, telomere shortening limits hematopoiesis capacity to a very limited extent.
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.
Aging Cell, 2019
Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐a...
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...
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.
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.
No Association Between Telomere Length and Blood Cell Counts in Elderly Individuals
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2009
Telomeres play a crucial role in maintaining the physical integrity of chromosomes. Telomere length (TL) is severely reduced in individuals with dyskeratosis congenita and a number of other bone marrow failure syndromes. The TL of healthy individuals is highly variable, but shortens with age. It is presently unclear if variations in TL observed in normal aging individuals affect significantly their hematopoietic reserve. Method We studied the correlation between leukocyte age-adjusted TL (aTL) and blood cell parameters (total leukocytes, neutrophils, monocytes, eosinophils, lymphocytes, hemoglobin, and platelets) in a large cohort (n=717) of women aged 38-100 years. Result We did not find any significant correlation between aTL and blood counts. Our data suggest that the aTL of aging individuals is not significantly predictive of their hematopoietic reserve, which implies that TL measurement may not be clinically useful in the selection of hematopoietic stem cell transplantation donors.
Is Telomere Length a Biomarker of Aging? A Review
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2011
Telomeres,theDNA-proteinstructureslocatedattheendsofchromosomes,havebeenproposedtoactasabiomarkerof aging.Inthisreview,thehumanevidencethattelomerelengthisabiomarkerofagingisevaluated.Althoughtelomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal.Morestudiesexaminingtherelationshipsbetweentelomerelengthandmortalityandwithmeasuresthatdeclinewith"normal"agingincommunitysamplesarerequired.Thesestudieswouldbenefitfromlongitudinalmeasures ofbothtelomerelengthandaging-relatedparameters.
Aging Cell, 2007
Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.