Dataset Information

Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.

ABSTRACT:

Objectives

Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age--known as "epigenetic clocks"--have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are "sensitive periods" when adversity is most impactful.

Methods

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n?=?973), we tested the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7.5 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated potential sensitive period effects.

Results

We found that exposure to abuse, financial hardship, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of Hannum-based epigenetic age from chronological age, even after considering the role of adversity accumulation and recency. Secondary sex-stratified analyses identified particularly strong sensitive period effects. These effects were undetected in analyses comparing children "exposed" versus "unexposed" to adversity. We did not identify any associations between adversity and epigenetic age using the Horvath epigenetic clock.

Conclusions

Our results suggest that adversity may alter methylation processes in ways that either directly or indirectly perturb normal cellular aging and that these effects may be heightened during specific life stages.

SUBMITTER: Marini S

PROVIDER: S-EPMC7832214 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.

Marini Sandro S Davis Kathryn A KA Soare Thomas W TW Zhu Yiwen Y Suderman Matthew J MJ Simpkin Andrew J AJ Smith Andrew D A C ADAC Wolf Erika J EJ Relton Caroline L CL Dunn Erin C EC

Psychoneuroendocrinology 20191106

<h4>Objectives</h4>Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age--known as "epigenetic clocks"--have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are "sensitive periods" when ...[more]

PMID: 31918390

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Project description:ImportanceA growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA may be associated with an increased risk for age-related disease. These investigations, however, have been predominantly cross-sectional and focused on adults and females.ObjectiveTo evaluate associations of threat-related (ie, physical abuse) and deprivation-related (ie, emotional neglect) ELA exposure with cellular and reproductive strategy metrics of biological aging among boys and girls with specific genetic backgrounds around the period of pubertal onset.Design, setting, and participantsIn this cohort study, 997 boys and girls in grade 1 to grade 3 from 3 large elementary schools were recruited from Bengbu, Anhui Province, China, and were followed up from March 21, 2016 (baseline; wave 1), for 4 consecutive years, through March 25, 2019.Main outcomes and measuresThe outcome was accelerated biological aging in both cellular and reproductive strategy metrics: telomere attrition and age at thelarche (for girls) and testicular maturation (for boys). Multi-informant assessment of exposure to threat-related and deprivation-related ELA was done at baseline (wave 1) and 1-year follow-up (wave 2). The polygenic risk score (PRS) was computed based on 17 single-nucleotide variations for early pubertal timing.ResultsOf the 997 participants (579 girls [58.1%]; mean [SD] age at baseline, 8.0 [0.8] years), 550 (55.2%) reported exposure to threat-related ELA and 443 (44.4%) reported exposure to deprivation-related ELA. Threat-related ELA was associated with onset of thelarche 2.6 months earlier and deprivation-related ELA with onset of thelarche 3.3 months earlier in exposed girls than in unexposed peers; these associations were observed only among girls with a low PRS. Among boys, a similar pattern was found. Threat-related ELA was associated with testicular volume of 4 mL or more 1.4 months earlier and deprivation-related ELA was associated with testicular volume of 4 mL or more 2.3 months earlier than in unexposed peers but only among those with a low PRS. Boys and girls with greater exposure to threats showed a significantly higher percentage of telomere length change during 1-year follow-up, but only among those with low PRS (boys: β = 1.50; 95% CI, 0.80-2.21; P < .001; girls: β = 2.40; 95% CI, 1.78-3.05; P < .001) and moderate PRS (boys: β = 1.09; 95% CI, 0.43-1.75; P = .001; and girls: β = 1.27; 95% CI, 0.77-1.77; P < .001). No associations of deprivation-related ELA with percentage of telomere length change were found.Conclusions and relevanceThis study suggests that the accelerating association of ELA with biological aging might occur at an earlier age and in a genetic background-dependent and dimension-specific manner.

Dataset Information

Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.

Objectives

Methods

Results

Conclusions

Publications

Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.

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