Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Altos Labs, San Diego Institute of Science, San Diego, CA, USA.
Nat Aging. 2023 Sep;3(9):1144-1166. doi: 10.1038/s43587-023-00462-6. Epub 2023 Aug 10.
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.
衰老通常被认为是随机细胞损伤的结果，可以通过 DNA 甲基化谱进行准确估计，这是泛组织表观遗传钟的基础。在这里，我们使用来自哺乳动物甲基化联盟的 11754 个甲基化阵列展示了通用的泛哺乳动物时钟的开发，这些阵列涵盖了 185 种哺乳动物的 59 种组织类型。这些预测模型可以非常准确地估计哺乳动物组织的年龄（r > 0.96）。年龄偏差与人类死亡风险、小鼠生长轴突变和热量限制有关。我们确定了一些具有特定甲基化水平的胞嘧啶，这些水平随着年龄的变化在许多物种中都发生了变化。这些位点高度富集在多梳抑制复合物 2 结合的位置附近，与哺乳动物发育、癌症、肥胖和长寿相关的基因有关。我们的研究结果提供了新的证据，表明衰老在所有哺乳动物中是保守的，与发育过程交织在一起。
