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

Pepper, Gillian; Bateson, Melissa; Nettle, Daniel

doi:10.1098/rsos.180744

Cited by 74 publications

(63 citation statements)

References 57 publications

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“…Although it is clear that telomere length is substantially heritable, perhaps accounting for as much as 70% of the variance in telomere length (Broer et al, 2013;Hjelmborg et al, 2015), such estimates clearly leave room for environmental effects. In fact, despite substantial genetic influence on telomere length before birth, twin studies indicate that environmental factors are the dominant source of influence across the life span (Bakaysa et al, 2007), a finding consistent with a recent meta-analysis linking exposure to stress and adversity with shorter telomeres (Pepper, Bateson, & Nettle, 2018).…”

Section: Hypothesis 1: Effects Of Adversity On Telomeressupporting

confidence: 74%

Testing three hypotheses about effects of sensitive–insensitive parenting on telomeres.

Beijers¹,

Hartman²,

Shalev³

et al. 2020

Developmental Psychology

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Telomeres are the protective DNA-protein sequences appearing at the ends of chromosomes; they shorten with each cell division and are considered a biomarker of aging. Shorter telomere length and greater erosion have been associated with compromised physical and mental health and are hypothesized to be affected by early life stress. In the latter case, most work has relied on retrospective measures of early life stressors. The Dutch research (n ϭ 193) presented herein tested 3 hypotheses prospectively regarding effects of sensitive-insensitive parenting during the first 2.5 years on telomere length at age 6, when first measured, and change over the following 4 years. It was predicted that (1) less sensitive parenting would predict shorter telomeres and greater erosion and that such effects would be most pronounced in children (2) exposed to prenatal stress and/or (3) who were highly negatively emotional as infants. Results revealed, only, that prenatal stress amplified parenting effects on telomere change-in a differentialsusceptibility-related manner: Prenatally stressed children displayed more erosion when they experienced insensitive parenting and less erosion when they experienced sensitive parenting. Mechanisms that might initiate greater postnatal plasticity as a result of prenatal stress are highlighted and future work outlined.

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Section: Hypothesis 1: Effects Of Adversity On Telomeressupporting

confidence: 74%

Testing three hypotheses about effects of sensitive–insensitive parenting on telomeres.

Beijers¹,

Hartman²,

Shalev³

et al. 2020

Developmental Psychology

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“…Leucocyte telomere length (LTL)—the length of the repeated TTAGGG sequence at the end of leucocyte chromosomes—is an extensively studied biomarker of human health and well-being. In support of a link between poorer health and shorter average LTL, many cross-sectional studies have found an association between tobacco smoking and shorter LTL [1,2]. Since human telomeres shorten with age, these data are widely interpreted as demonstrating that smoking accelerates the rate of biological ageing [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts

et al. 2019

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Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr −1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr −1 . Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.

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“…To illustrate with some concrete numbers, according to our simulations, repeatability of the TS ratio should be about 0.80 with error σ values of 0.05, 0.51 with error σ values of 0.1, and 0.28 with error σ values of 0.15. A widespread conclusion when surveying the qPCR telomere epidemiology literature is that there is a great deal of heterogeneity between studies [29,30]. Our findings suggest that small differentials in errors in the laboratory would be sufficient to drive large heterogeneity in outcomes.…”

Section: Discussionmentioning

confidence: 74%

Consequences of measurement error in qPCR telomere data: A simulation study

Nettle

Seeker

Nussey

et al. 2018

Preprint

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The qPCR method provides an inexpensive, rapid method for estimating relative average telomere length across a set of biological samples. Like all laboratory methods, it involves some degree of measurement error. The estimation of relative telomere length is done subjecting the actual measurements made (the Cq values for telomere and a control gene) to non-linear transformations and combining them into a ratio. Here, we use computer simulations, supported by mathematical analysis, to explore how errors in measurement affect qPCR estimates of relative telomere length, both in cross-sectional and longitudinal data. We show that errors introduced at the level of Cq values are magnified when the TS ratio is calculated. If the errors at the Cq level are normally distributed and independent of telomere length, those in the TS ratio are positively skewed and proportional to telomere length. The repeatability of the TS ratio declines abruptly with increasing error in measurement of the telomere sequence and/or the control gene. In simulated longitudinal data, measurement error alone can produce a pattern of low correlation between successive measures of telomere length, coupled with a strong dependency of the rate of change on initial telomere length.Our results illustrate the importance of control of measurement error: a small increase in error in Cq values can have large consequences for the power and interpretability of qPCR estimates of relative telomere length. They also illustrate the importance of characterising the measurement error that exists in each dataset-coefficients of variation are generally unhelpful, and researchers should report standard deviations of Cq values and/or repeatabilities of TS ratios-and allowing for the known effects of measurement error when interpreting patterns of TS ratio change over time.

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

Cited by 74 publications

References 57 publications

Testing three hypotheses about effects of sensitive–insensitive parenting on telomeres.

Testing three hypotheses about effects of sensitive–insensitive parenting on telomeres.

Smoking does not accelerate leucocyte telomere attrition: a meta-analysis of 18 longitudinal cohorts

Consequences of measurement error in qPCR telomere data: A simulation study

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