DNA methylation and healthy human aging.
DNA methylation and healthy human aging.
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DOI：
10.1111/acel.12349
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发表时间：
2015-12
期刊：
影响因子：
7.8
通讯作者：
Kobor MS
中科院分区：
文献类型：
--
作者：
Jones MJ;Goodman SJ;Kobor MS
衰老的过程导致细胞和分子水平的一系列变化，包括衰老、端粒缩短和基因表达的变化。表观遗传模式也会随着寿命的延长而变化，这表明表观遗传变化可能构成衰老过程的一个重要组成部分。研究最多的表观遗传标记是DNA甲基化，即CpG二核苷酸中甲基的存在。这些二核苷酸通常位于基因启动子附近，与基因表达水平有关。早期的研究表明，全球DNA甲基化水平在生命的头几年里增加，然后在成年后期开始下降。最近，随着微阵列和下一代测序技术的出现，人们观察到DNA甲基化的变异性随年龄的增加而增加，并发现了一些特定的位点模式。研究还表明，某些CpG位点与年龄高度相关，以至于使用少量这些位点的预测模型可以准确地预测捐赠者的实际年龄。总之，这些观察指出了两种现象的存在，这两种现象都有助于与年龄相关的DNA甲基化变化：表观遗传漂移和表观遗传时钟。在这篇综述中，我们关注人类一生中的健康衰老，并讨论DNA甲基化的动态以及基因组、环境和表观基因组之间的相互作用如何影响衰老速度。我们还讨论了确定‘表观遗传年龄’对人类健康的影响，并概述了对现有和未来研究的一些重要警告。
The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.