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

Riccardo E Marioni,Sarah E Harris,Naomi R Wray,Adele Taylor,Alison Pattie,Ian J Deary,Janie Corley,Stuart J Ritchie,Lee Murphy,Peter M Visscher,John M Starr,Paul Redmond,Allan F Mcrae,Sonia Shah,Graciela Muniz-Terrera,Steve Horvath,Jude Gibson,Simon R Cox

doi:10.1093/ije/dyu277

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.

Highlights

DNA methylation is an epigenetic marker that influences gene expression via the addition of a methyl group to cytosine nucleotides across the genome at cytosine-phosphateguanine (CpG) sites.[1]
Walking speed decreased over the waves, taking 3.9 s to walk 6 m at wave 1 compared with 4.7 s at wave 3.Compared with the participants with methylation data who completed more than one wave, those with methylation data from the first time point were slightly older with lower cognitive scores, poorer fitness scores and a higher methylation age (Supplementary Table 1, available as Supplementary data at IJE online)
We found significant cross-sectional correlations at age about 70 years between age acceleration and fluid cognitive ability, grip strength and lung function; higher methylation age acceleration was linked to poorer fitness

Summary

Introduction

DNA methylation is an epigenetic marker that influences gene expression via the addition of a methyl group to cytosine nucleotides across the genome at cytosine-phosphateguanine (CpG) sites.[1]. One set of variables that may run in parallel with a biological clock are those that reflect fitness or general health and well-being.[8] Markers of fitness include cognitive ability, grip strength, walking speed and lung function; lower levels in all of these measures are predictors of premature mortality.[9,10,11,12,13,14,15,16]. 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. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures

Methods

Results

Conclusion