DNA methylation age and physical and cognitive ageing

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Maddock, Jane 
Castillo-Fernandez, Juan 
Wong, Andrew 
Cooper, Rachel 
Richards, Marcus 


DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. Methods

AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. Results

AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p<0.05). In a subset of NSHD participants(n=482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance. Conclusions

We found little evidence to support associations between the first generation of DNAm-based biomarkers of ageing and age-related physical or cognitive performance in mid-life to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual’s health-span as proposed.

Cognitive aging, Functional performance, Normative aging, Physical performance, Aged, Aged, 80 and over, Aging, Cognitive Aging, DNA Methylation, Female, Humans, Male, Middle Aged
Journal Title
The Journals of Gerontology: Series A
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Oxford University Press (OUP)
Medical Research Council (MC_UU_12015/2)
MRC (MC_UU_00006/2)
This work was supported by the Economic and Social Research Council/Biotechnology and Biological Sciences Research Council [ES/N000404/1] and the UK Medical Research Council (MC_UU_12015/2).The UK Medical Research Council also provides core funding for the MRC National Survey of Health and Development and support for AW, RC, DK and RH [MC_UU_12019/1, MC_UU_12019/2, MC_UU_12019/4]. JM is supported by CLOSER through the Economic and Social Research Council [547821 GA3 ESRC]. The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007–2013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London