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Title: Universal DNA methylation age across mammalian tissues
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.

 
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Award ID(s):
2017803
NSF-PAR ID:
10481148
Author(s) / Creator(s):
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Publisher / Repository:
Nature Aging
Date Published:
Journal Name:
Nature Aging
Volume:
3
Issue:
9
ISSN:
2662-8465
Page Range / eLocation ID:
1144 to 1166
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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