title: The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936.
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.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK, Queensland Brain Institute, and.
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Queensland Brain Institute, and Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.affiliation: Queensland Brain Institute, and Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Allan F
authors.initials: AF
authors.lastname: McRae
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Ritchie
authors.affiliation: MRC Unit for Lifelong Health and Ageing, London, UK.
authors.forename: Graciela
authors.initials: G
authors.lastname: Muniz-Terrera
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: Wellcome Trust Clinical Research Facility, and.
authors.forename: Jude
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Redmond
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Cox
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Pattie
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Janie
authors.initials: J
authors.lastname: Corley
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Adele
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Wellcome Trust Clinical Research Facility, and.
authors.forename: Lee
authors.initials: L
authors.lastname: Murphy
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK and.
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: Gonda Research Center, David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Queensland Brain Institute, and Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.affiliation: Translational Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, and Department of Psychology, University of Edinburgh, Edinburgh, UK, i.deary@ed.ac.uk.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D000368:Aged; D000375:Aging / Q000523:psychology*; D015415:Biomarkers; D003071:Cognition; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D018737:Hand Strength; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D010809:Physical Fitness; D012129:Respiratory Function Tests; D012606:Scotland; D016138:Walking
chemical_list: D015415:Biomarkers
keywords: DNA methylation; cognitive function; epigenetic clock; fitness; longitudinal