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.

中文翻译：

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敏感时期的逆境暴露预示着儿童表观遗传衰老加速

目标 暴露于逆境与加速生物衰老有关，这反过来又被证明可以预测许多身心健康问题。近年来，基于 DNA 甲基化的表观遗传年龄测量（称为“表观遗传时钟”）已被用来估计加速的表观遗传衰老。尽管少数研究发现逆境暴露对儿童表观遗传年龄有影响，但没有人调查是否存在逆境影响最大的“敏感期”。方法 使用来自雅芳父母和儿童纵向研究 (ALSPAC；n = 973) 的数据，我们测试了重复测量童年经历七种逆境与使用 Horvath 和 Hannum 表观遗传时钟在 7.5 岁时评估的表观遗传年龄之间的前瞻性关联。 。通过最小角度回归变量选择程序，我们评估了潜在的敏感期效应。结果我们发现，即使在考虑了逆境积累和新近经历的作用之后，在儿童早期和中期的敏感时期遭受虐待、经济困难或邻里不利条件最能解释基于汉纳姆的表观遗传年龄与实际年龄偏差的变异性。次要性别分层分析发现特别强烈的敏感期效应。在比较“暴露”与“未暴露”逆境的儿童的分析中，没有发现这些影响。使用霍瓦斯表观遗传时钟，我们没有发现逆境与表观遗传年龄之间存在任何关联。结论我们的结果表明，逆境可能会以直接或间接扰乱正常细胞衰老的方式改变甲基化过程，并且这些影响可能在特定的生命阶段加剧。