Systematic underestimation of the epigenetic clock and age acceleration in older subjects

Publication type

Journal Article

Published in

Genome Biology

Authors

Louis Y. El Khoury, Tyler Gorrie-Stone, Melissa Smart, Amanda Hughes, Yanchun Bao, Alexandria Andrayas, Joe Burrage, Eilis Hannon, Meena Kumari, Jonathan Mill and Leonard C. Schalkwyk

Publication date

Summary

Background:
The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments.
Results:
The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways.
Conclusions:
The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.

Volume

20:283

DOI

https://doi.org/10.1186/s13059-019-1810-4

ISSN

16

Subjects

Older People, Life Course Analysis, Biology and Genetics

Notes

Open Access; This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.