Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.
Adversity exposure during sensitive periods predicts accelerated epigenetic aging in children.
复制标题
DOI：
10.1016/j.psyneuen.2019.104484
复制
发表时间：
2020-03
影响因子：
3.7
通讯作者：
Dunn EC
中科院分区：
文献类型：
--
作者：
Marini S;Davis KA;Soare TW;Zhu Y;Suderman MJ;Simpkin AJ;Smith ADAC;Wolf EJ;Relton CL;Dunn EC
逆境与加速生物衰老有关，而生物衰老反过来又被证明可以预测许多身体和精神健康问题。近年来，基于DNA甲基化的表观遗传年龄测量——被称为“表观遗传时钟”——已被用于估计加速的表观遗传衰老。虽然有少数研究发现逆境暴露对儿童表观遗传年龄有影响，但没有一项研究调查是否存在逆境影响最大的“敏感期”。使用雅芳父母与儿童纵向研究（ALSPAC; n=973）的数据，我们测试了在7.5岁时使用Horvath和Hannum表观遗传时钟评估的儿童暴露于7种逆境的重复测量与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。我们发现，即使在考虑了逆境积累和新近的作用后，童年早期和中期敏感时期的虐待、经济困难或邻里不利环境也能最好地解释汉纳姆表观遗传年龄与实足年龄偏差的变异性。二级性别分层分析确定了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Horvath表观遗传时钟，我们没有发现逆境和表观遗传年龄之间的任何关联。我们的研究结果表明，逆境可能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。
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. 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. 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. 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.
登录
查看更多内容
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
通讯作者：
Brenner H
影响因子：
7.4
作者：
Dunn, Erin C.;Gilman, Stephen E.;Molnar, Beth E.
通讯作者：
Molnar, Beth E.
影响因子：
3.5
作者：
Lawn RB;Anderson EL;Suderman M;Simpkin AJ;Gaunt TR;Teschendorff AE;Widschwendter M;Hardy R;Kuh D;Relton CL;Howe LD
通讯作者：
Howe LD
青春期女孩 DNA 甲基化年龄加速：与昼夜皮质醇升高和海马体积减少有关。
影响因子：
6.8
作者：
Davis EG;Humphreys KL;McEwen LM;Sacchet MD;Camacho MC;MacIsaac JL;Lin DTS;Kobor MS;Gotlib IH
通讯作者：
Gotlib IH