Systematic Underestimation of the Epigenetic Clock and Age Acceleration in Older Subjects

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2019 Dec 19

PMID 31847916

Citations 55

Authors

Louis Y El Khoury

Tyler Gorrie-Stone

Melissa Smart

Amanda Hughes

Yanchun Bao

Alexandria Andrayas

Joe Burrage

Eilis Hannon

Meena Kumari

Jonathan Mill

Leonard C Schalkwyk

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Epigenetic ageing clocks: statistical methods and emerging computational challenges.

Teschendorff A, Horvath S Nat Rev Genet. 2025; .

PMID: 39806006 DOI: 10.1038/s41576-024-00807-w.

Exploratory DNA methylation analysis in post-mortem heart tissue of sudden unexplained death.

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Probabilistic inference of epigenetic age acceleration from cellular dynamics.

Dabrowski J, Yang E, Crofts S, Hillary R, Simpson D, McCartney D Nat Aging. 2024; 4(10):1493-1507.

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Common DNA sequence variation influences epigenetic aging in African populations.

Meeks G, Scelza B, Asnake H, Prall S, Patin E, Froment A bioRxiv. 2024; .

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