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Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

ABSTRACT: Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.

SUBMITTER: Entringer S

PROVIDER: S-EPMC3158153 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

Entringer Sonja S Epel Elissa S ES Kumsta Robert R Lin Jue J Hellhammer Dirk H DH Blackburn Elizabeth H EH Wüst Stefan S Wadhwa Pathik D PD

Proceedings of the National Academy of Sciences of the United States of America 20110803 33

Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested t ...[more]

PMID: 21813766

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Project description:BackgroundFrailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty.MethodsWe utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal.ResultsFrail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13).ConclusionsInter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.

Dataset Information

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

Publications

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.

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