Research Paper|Volume 17, Issue 3|pp 685—698

DNA methylation entropy is a biomarker for aging

Jonathan Chan¹, Liudmilla Rubbi², Matteo Pellegrini²

¹Computational and Systems Biology Interdepartmental Program at University of California, Los Angeles, Los Angeles, CA 90095, USA
²Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA

Received: February 13, 2024Accepted: February 13, 2025Published: March 12, 2025

https://doi.org/10.18632/aging.206220

Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The dynamic nature of epigenetic modifications has been leveraged to construct epigenetic clocks that accurately predict an individual’s age based on DNA methylation levels. Here we explore whether the accumulation of epimutations, which can be quantified by Shannon’s entropy, changes reproducibly with age. Using targeted bisulfite sequencing, we analyzed the associations between age, entropy, and methylation levels in human buccal swab samples. We find that epigenetic clocks based on the entropy of methylation states predict chronological age with similar accuracy as common approaches that are based on methylation levels of individual cytosines. Our approach suggests that across many genomic loci, methylation entropy changes reproducibly with age.