Universal DNA methylation age across mammalian tissues

Authors

A. T. Lu, University of California, Los Angeles
Jessica Lynn Petersen, University of Nebraska - LincolnFollow
Steve Horvath, Departments of Human Genetics and Biostatistics, University of California at Los AngelesFollow
et al., et al.

Document Type

Article

Date of this Version

8-10-2023

Citation

Nature Aging, Volume 3, September 2023, pp.1144–1166

doi:10.1038/s43587-023-00462-6

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License,

Abstract

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.