Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume.
Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume.
复制标题
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。
DOI：
10.1038/tp.2017.188
复制
发表时间：
2017-08-29
影响因子：
6.8
通讯作者：
Gotlib IH
中科院分区：
文献类型：
--
作者：
Davis EG;Humphreys KL;McEwen LM;Sacchet MD;Camacho MC;MacIsaac JL;Lin DTS;Kobor MS;Gotlib IH
许多研究表明，通过皮质醇（压力反应系统的产物）对细胞衰老过程的影响，暴露于压力与不良健康结果有关。加速DNA甲基化年龄是一个有前途的表观遗传标记与压力和疾病的风险，可能构成了一个链接，从压力反应的变化，在神经结构。具体来说，糖皮质激素信号的升高可能有助于加速DNA甲基化年龄，这可能意味着一个适应不良的压力相关的级联反应，导致海马萎缩。我们研究了46名青春期女孩的昼夜皮质醇水平，DNA甲基化年龄和海马体积之间的关系在纵向研究。我们计算了两个每日皮质醇收集期的曲线下面积，并使用先前建立的基于一组与实足年龄相关的CpG位点的方法计算了DNA甲基化年龄。我们计算了一个剩余的分数，偏出实足年龄，较高的差异反映了相对加速的DNA甲基化年龄。我们通过T1加权图像和自动体积分割评估海马体积。我们发现，更大的昼夜皮质醇生产与加速DNA甲基化年龄，这反过来又与左海马体积减少。最后，加速DNA甲基化年龄显着介导昼夜皮质醇和左海马体积之间的关联。因此，加速的DNA甲基化年龄可能是下丘脑-垂体-肾上腺轴失调与神经结构联系的表观遗传标记。如果这些发现被复制，目前的研究提供了一种方法，以促进我们对糖皮质激素信号传导与细胞衰老和大脑发育相关的机制的理解。
Numerous studies have linked exposure to stress to adverse health outcomes through the effects of cortisol, a product of the stress response system, on cellular aging processes. Accelerated DNA methylation age is a promising epigenetic marker associated with stress and disease risk that may constitute a link from stress response to changes in neural structures. Specifically, elevated glucocorticoid signaling likely contributes to accelerating DNA methylation age, which may signify a maladaptive stress-related cascade that leads to hippocampal atrophy. We examined the relations among diurnal cortisol levels, DNA methylation age and hippocampal volume in a longitudinal study of 46 adolescent girls. We computed area under the curve from two daily cortisol collection periods, and calculated DNA methylation age using previously established methods based on a set of CpG sites associated with chronological age. We computed a residual score by partialling out chronological age; higher discrepancies reflect relatively accelerated DNA methylation age. We assessed hippocampal volume via T1-weighted images and automated volumetric segmentation. We found that greater diurnal cortisol production was associated with accelerated DNA methylation age, which in turn was associated with reduced left hippocampal volume. Finally, accelerated DNA methylation age significantly mediated the association between diurnal cortisol and left hippocampal volume. Thus, accelerated DNA methylation age may be an epigenetic marker linking hypothalamic–pituitary–adrenal axis dysregulation with neural structure. If these findings are replicated, the current study provides a method for advancing our understanding of mechanisms by which glucocorticoid signaling is associated with cellular aging and brain development.
登录
查看更多内容
影响因子：
5.7
作者：
Jovicich J;Czanner S;Han X;Salat D;van der Kouwe A;Quinn B;Pacheco J;Albert M;Killiany R;Blacker D;Maguire P;Rosas D;Makris N;Gollub R;Dale A;Dickerson BC;Fischl B
通讯作者：
Fischl B
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：
7.8
作者：
Jones MJ;Goodman SJ;Kobor MS
通讯作者：
Kobor MS
影响因子：
3.3
作者：
Chen, Li;Pan, Hong;Holbrook, Joanna D.
通讯作者：
Holbrook, Joanna D.