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DNA Methylation Age and Physical and Cognitive Aging

Lookup NU author(s): Professor Rachel CooperORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. Background: 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 aging 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 = 1,388-1,685). For example, a 1-year increase in AgeAccelPheno or AgeAccelGrim was associated with a 0.01 mL (95% confidence interval [CI]: 0.01, 0.02) or 0.03 mL (95% CI: 0.01, 0.05) lower mean FEV1 respectively. 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 <. 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 aging and age-related physical or cognitive performance in midlife to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual's healthspan as proposed.

Publication metadata

Author(s): Maddock J, Castillo-Fernandez J, Wong A, Cooper R, Richards M, Ong KK, Ploubidis GB, Goodman A, Kuh D, Bell JT, Hardy R

Publication type: Article

Publication status: Published

Journal: Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Year: 2020

Volume: 75

Issue: 3

Pages: 504-511

Print publication date: 01/03/2020

Online publication date: 20/10/2019

Acceptance date: 08/10/2019

Date deposited: 17/01/2022

ISSN (print): 1079-5006

ISSN (electronic): 1758-535X

Publisher: Oxford University Press


DOI: 10.1093/gerona/glz246

PubMed id: 31630156


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Funder referenceFunder name
547821 GA3 ESRC