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Zane Koch¹, Adam Li¹, Trey Ideker^1,2,3

¹Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, California, USA.

|January 27, 2026

Summary

Epigenetic remodeling, including histone modification and DNA methylation, shows coordinated changes with aging across multiple tissues. An epigenetic clock developed from these changes accurately predicts biological age in humans and mice.

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Area of Science:

Epigenetics and aging research
Molecular biology of aging
Comparative genomics

Background:

Epigenetic alterations are key features of the aging process.
The interplay between different epigenetic layers (e.g., histone marks, DNA methylation) during aging is not fully understood.
Comprehensive analysis across multiple tissues and species is needed to elucidate these relationships.

Purpose of the Study:

To comprehensively analyze age-related changes across multiple epigenetic layers (histone marks and DNA methylation).
To investigate the interrelationship between different epigenetic modifications during aging.
To develop and validate a predictive epigenetic clock for biological age.

Main Methods:

Analysis of 6 histone marks and DNA methylation across 12 tissues in over 1000 humans and mice.
Development of an epigenetic clock based on genes identified through synchronized epigenetic changes.
Validation of the clock's predictive accuracy using Spearman correlation.

Main Results:

A synchronized pattern of age-related epigenetic changes was observed across histone modifications and DNA methylation.
These coordinated changes converge on a common set of genes.
An epigenetic clock derived from these genes accurately predicted age across different epigenetic layers (Spearman ρ: 0.70 in humans, 0.81 in mice).
Histone modification and DNA methylation profiles consistently predicted individual aging rates.

Conclusions:

Epigenetic modifications undergo coordinated remodeling throughout the lifespan.
This coordinated remodeling provides a unified perspective on epigenetic aging.
The findings support a holistic view of epigenetic aging influenced by multiple, interrelated molecular mechanisms.