Universal DNA methylation age across mammalian tissues.
Universal DNA methylation age across mammalian tissues.
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DOI：
10.1038/s43587-023-00462-6
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发表时间：
2023-09
影响因子：
7
通讯作者：
Horvath, Steve
中科院分区：
文献类型：
--
作者：
Lu, Viviana Perez Ake;Fei, Zhe;Raj, Ken;Horvath, Steve
衰老，通常被认为是随机细胞损伤的结果，可以使用DNA甲基化谱准确估计，这是泛组织表观遗传时钟的基础。在这里，我们展示了通用泛哺乳动物时钟的发展，使用来自我们的哺乳动物甲基化联盟的11，754个甲基化阵列，其中包括185种哺乳动物物种的59种组织类型。这些预测模型估计哺乳动物组织年龄具有高精度（r > 0.96）。年龄偏差与人类死亡风险、小鼠生长激素轴突变和热量限制相关。我们确定了甲基化水平随许多物种年龄变化的特定胞嘧啶。这些位点高度富集在polycomb抑制复合物2结合位点，接近与哺乳动物发育、癌症、肥胖和长寿有关的基因。我们的研究结果提供了新的证据，表明衰老在进化上是保守的，并与所有哺乳动物的发育过程交织在一起。本研究鉴定和表征了哺乳动物中与年龄相关的进化保守的胞嘧啶甲基化模式，并建立了泛哺乳动物表观遗传时钟。
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals. This study identifies and characterizes evolutionarily conserved cytosine methylation patterns related to age across mammals and establishes pan-mammalian epigenetic clocks.