德纳姆
表观遗传学
DNA甲基化
生物
计算生物学
CpG站点
转录组
后生
进化生物学
遗传学
基因
基因表达
作者
Andrei E. Tarkhov,Thomas Lindstrom-Vautrin,Sirui Zhang,Kejun Ying,Mahdi Moqri,Bohan Zhang,Alexander Tyshkovskiy,Orr Levy,Vadim N. Gladyshev
标识
DOI:10.1101/2022.09.26.509592
摘要
Abstract Age-related changes in DNA methylation (DNAm) form the basis for the development of most robust predictors of age, epigenetic clocks, but a clear mechanistic basis for exactly what part of the aging process they quantify is lacking. Here, to clarify the nature of epigenetic aging, we juxtapose the aging dynamics of tissue and single-cell DNAm (scDNAm) with scDNAm changes during early development, and corroborate our analyses with a single-cell RNAseq analysis within the same multi-omics dataset. We show that epigenetic aging involves co-regulated changes, but it is dominated by the stochastic component, and this agrees with transcriptional coordination patterns. We further support the finding of stochastic epigenetic aging by direct tissue and single-cell DNAm analyses and modeling of aging DNAm trajectories with a stochastic process akin to radiocarbon decay. Finally, we describe a single-cell algorithm for the identification of co-regulated and stochastic CpG clusters showing consistent transcriptomic coordination patterns, providing new opportunities for targeting aging and evaluating longevity interventions.
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