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. 2015 Aug;44(4):1388-96.
doi: 10.1093/ije/dyu277. Epub 2015 Jan 22.

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Riccardo E Marioni  1 , Sonia Shah  2 , Allan F McRae  2 , Stuart J Ritchie  3 , Graciela Muniz-Terrera  4 , Sarah E Harris  5 , Jude Gibson  6 , Paul Redmond  7 , Simon R Cox  3 , Alison Pattie  7 , Janie Corley  7 , Adele Taylor  7 , Lee Murphy  6 , John M Starr  8 , Steve Horvath  9 , Peter M Visscher  10 , Naomi R Wray  11 , Ian J Deary  12
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The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Riccardo E Marioni et al. Int J Epidemiol. 2015 Aug.

Abstract

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability.

Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures.

Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits.

Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up.

Keywords: DNA methylation; cognitive function; epigenetic clock; fitness; longitudinal.

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Figures

Figure 1.
Figure 1.
Individual trajectories and mean rate of change in DNA methylation age over time.
Figure 2.
Figure 2.
Epigenome-wide association study Manhattan plots for the four fitness traits. The lines indicate the Bonferroni significant P-value threshold (P = 0.05/450,726 = 1.1 x 10−7) and nominal significance (P = 1 x 10−5). gf, fluid type general intelligence; FEV1, forced expiratory volume in one second.
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