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

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*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

3 Citations (Scopus)
80 Downloads (Pure)

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.

Original languageEnglish
Article number283
Number of pages10
JournalGenome Biology
Volume20
Issue number1
DOIs
Publication statusPublished - 17 Dec 2019

Keywords

  • Age acceleration
  • DNA methylation
  • Epigenetic clock

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