Bateson, M. | bioRxiv Science

bioRxiv2018

Telomeres as integrative markers of exposure to stress and adversity: A systematic review and meta-analysis

Telomeres have been proposed as a biomarker that integrates the impacts of different kinds of stress and adversity into a common currency. There has as yet been no overall comparison of how different classes of exposure associate with telomeres. We present a meta-analysis of the literature relating telomere measures to stresses and adversities in humans. The analysed dataset contained 543 associations from 138 studies involving 402,116 people. Overall, there was a weak association between telomere variables and exposures (greater adversity, shorter telomeres: r = -0.15, 95% CI - 0.18 to -0.11). This was not driven by any one type of exposure, since significant associations were found separately for physical diseases, environmental hazards, nutrition, psychiatric illness, smoking, physical activity, psychosocial and socioeconomic exposures. Methodological features of the studies did not explain any substantial proportion of the heterogeneity in association strength. There was, however, evidence consistent with publication bias, with unexpectedly strong negative associations reported by studies with small samples. Restricting analysis to sample sizes greater than 100 attenuated the overall association substantially (r = -0.09, 95% CI -0.13 to -0.05). Most studies were underpowered to detect the typical association magnitude. The literature is dominated by cross-sectional and correlational studies which makes causal interpretation problematic.

epidemiology↗

bioRxiv2016

Detecting telomere elongation in longitudinal datasets: Analysis of a proposal by Simons, Stulp and Nakagawa

Telomere shortening has emerged as an important biomarker of aging. Longitudinal studies consistently find that, although telomere length shortens over time on average, there is a subset of individuals for whom telomere length is observed to increase. This apparent lengthening could either be a genuine biological phenomenon, or simply due to measurement and sampling error. Simons, Stulp and Nakagawa [Biogerontology 15: 99-103, 2014] recently proposed a statistical test for detecting when the amount of apparent lengthening in a dataset exceeds that which should be expected due to error, and thus indicating that genuine elongation may be operative in some individuals. The test is however based on a restrictive assumption, namely that each individuals true rate of telomere change is constant over time. It is not currently known whether this assumption is true. Here we show, using simulated datasets, that with perfect measurement and large sample size, the test has high power to detect true lengthening as long as the true rate of shortening is either constant, or moderately stable, over time. If the true rate of lengthening varies randomly from year to year, the test systematically returns type-II errors. We also consider the impact of measurement error. Using estimates of the magnitude of annual attrition and of measurement error derived from the human telomere literature, we show that power of the test is likely to be low in several empirically-realistic scenarios, even in large samples. Thus, whilst a significant result of the proposed test is likely to indicate that true lengthening is present in a data set, type-II errors are a likely outcome, either if measurement error is substantial, and/or the true rate of attrition varies substantially over time within individuals.

epidemiology↗