Pan‐Epigenetic Age Prediction in Mammals

TL;DR

This study shows that epigenetic changes across multiple layers are synchronized during aging and can be used to predict age accurately in humans and mice.

Contribution

The paper introduces a unified 'pan-epigenetic' clock that integrates multiple epigenetic layers for age prediction.

Findings

Epigenetic layers show synchronized age-related changes across 12 tissues in humans and mice.

A pan-epigenetic clock predicts age with high accuracy using any epigenetic layer (ρ: 0.70 in humans, 0.81 in mice).

Histone and DNA methylation profiles agree on individuals aging faster or slower.

Abstract

Epigenetic remodeling is a hallmark of aging, yet which epigenetic layers are most affected during aging—and the extent to which they are interrelated—is not well understood. Here, we perform a comprehensive analysis of epigenetic aging encompassing 6 histone marks and DNA methylation measured across 12 tissues from > 1000 humans and mice. We identify a synchronized pattern of age‐related changes across these epigenetic layers, with all changes converging upon a common set of genes. Notably, an epigenetic clock based on these genes can accurately predict age using data from any layer (Spearman ρ: 0.70 in humans, 0.81 in mice). Applying this “pan‐epigenetic” clock, we observe that histone modification and DNA methylation profiles agree in the prediction of which individuals are aging more rapidly or slowly. These results demonstrate that epigenetic modifications are subject to coordinated remodeling over the lifespan, offering a unified view of epigenetic aging.

Across > 1000 human and mouse epigenomes, histone modifications and DNA methylation undergo coordinated, cross‐tissue remodeling at shared genes.

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