Dataset Information

The association between telomere length and mortality in Bangladesh.

ABSTRACT: Telomeres are tandem repeat sequences at the end of chromosomes that bind proteins to protect chromosome ends. Telomeres shorten with age, and shorter leukocyte telomere length (TL) has been associated with overall mortality in numerous studies. However, this association has not been tested in populations outside of Europe and the U.S. We assessed the association between TL and subsequent mortality using data on 744 mortality cases and 761 age-/sex-matched controls sampled from >27,000 participants from three longitudinal Bangladeshi cohorts: Health Effects of Arsenic Longitudinal Study (HEALS), HEALS Expansion (HEALS-E), and Bangladesh Vitamin E and Selenium Trial (BEST). We used conditional logistic regression to estimate odds ratios (ORs) for the association between a standardized TL variable and overall mortality, as well as mortality from chronic diseases, respiratory diseases, circulatory diseases, and cancer. In HEALS and BEST, we observed an association between shorter TL and increased overall mortality (P=0.03 and P=0.03), mortality from chronic disease (P=0.01 and P=0.03) and mortality from circulatory disease (P=0.03 and P=0.04). Results from pooled analyses of all cohorts were consistent with HEALS and BEST. This is the first study demonstrating an association between short TL and increased mortality in a population of non-European ancestry.

SUBMITTER: Dean SG

PROVIDER: S-EPMC5509454 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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The association between telomere length and mortality in Bangladesh.

Dean Samantha G SG Zhang Chenan C Gao Jianjun J Roy Shantanu S Shinkle Justin J Sabarinathan Mekala M Argos Maria M Tong Lin L Ahmed Alauddin A Islam Md Tariqul MT Islam Tariqul T Rakibuz-Zaman Muhammad M Sarwar Golam G Shahriar Hasan H Rahman Mahfuzar M Yunus Md M Graziano Joseph H JH Chen Lin S LS Jasmine Farzana F Kibriya Muhammad G MG Ahsan Habibul H Pierce Brandon L BL

Aging 20170601 6

Telomeres are tandem repeat sequences at the end of chromosomes that bind proteins to protect chromosome ends. Telomeres shorten with age, and shorter leukocyte telomere length (TL) has been associated with overall mortality in numerous studies. However, this association has not been tested in populations outside of Europe and the U.S. We assessed the association between TL and subsequent mortality using data on 744 mortality cases and 761 age-/sex-matched controls sampled from >27,000 participa ...[more]

PMID: 28630379

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Project description:ImportanceTelomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders.ObjectiveTo determine the association between LTL and overall as well as disease-specific mortality and morbidity.Design, setting, and participantsThis multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.Main outcomes and measuresHazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity.ResultsThis study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results.Conclusions and relevanceThis cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.

Project description:Background/objectivesTelomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age.Subjects/methodsSubjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years).ResultsWe identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted β-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (β=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (β=-0.025±0.0008; P=0.005) and WC (β=-0.0011±0.0004; P=0.007). High BF% (BF1%: β=-0.035±0.011; P=0.002; BF2%: β=-0.041±0.008; P<0.001) and WC (β=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality.ConclusionsObesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Dataset Information

The association between telomere length and mortality in Bangladesh.

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The association between telomere length and mortality in Bangladesh.

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