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.

DNA methylation age is associated with mortality in a longitudinal Danish twin study

“…This finding is supported by data from Marioni et al (2015b) who find that the Horvath clock underestimates the age in older individuals by approximately 4 years.…”

“…To this end, studies are now emerging which demonstrate that an accelerated DNAm age may be linked to disease development. For instance, a modest crosssectional association between accelerated methylation age and lower cognition, weaker grip strength, and poorer lung function was suggested by Marioni et al (2015b), although they could not document that DNAm age at intake could predict future decline in any of the measured parameters. In addition, a significantly accelerated DNAm age of both blood and brain tissue was seen in trisomy 21 individuals, perhaps mirroring the premature aging conditions often experienced by these individuals .…”

Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

“…Marioni et al reported significant correlations between the epigenetic clock and cognitive functioning, grip strength and lung function. 46 In addition, Breitling et al showed that the epigenetic clock was correlated with the FI and further confirmed the robustness of this association across diverse domains of health deficits. 45 Our previous study on the relationship between smoking-induced DNA methylation and the epigenetic clock intriguingly found 7 out of the 9 now identified loci to be associated with the epigenetic clock as well, 47 including cg01127300, cg02657160 (CPOX), cg05673882 (POLK), cg07826859 (MYO1G), cg14753356, cg19589396 and cg23667432 (ALPP).…”

“…42 Previous studies have evaluated its relationships with 2 other aging estimators, telomere length, 43,44 and age-related DNA methylation changes ("epigenetic clock"). 45,46 Telomere length was not associated with frailty, neither in Asian nor in Caucasian populations. 43,44 In contrast, the epigenetic clock was found to be significantly associated with frailty-related phenotypes and the FI.…”

DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis

“…Interestingly, obesity altered the epigenetic clock of the liver but not for any other tissue sites (11). Acceleration of this clock has functional implications, as age-accelerated DNAm correlates with poorer performance on physical and mental aptitude tests and higher overall mortality, even after adjusting for known risk factors (14,15). Thus, the Horvath clock can be assayed from peripheral blood, demonstrates concordance with tissue DNAm, and can be used to calculate accelerated aging to provide prognostic information.…”