Epigenetic age acceleration and midlife cognition: joint evidence from observational study and Mendelian randomization.

Yang Pan, Zhijie Huang, Xiao Sun, Ileana De Anda-Duran, Ruiyuan Zhang, Wei Chen, Changwei Li, Ana W Capuano, Kristine Yaffe, Jinying Zhao, David A Bennett, Owen T Carmichael, Lydia A Bazzano, Tanika N Kelly

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, IL, USA. · pubmed

Paper

Abstract

The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each associated with slower processing speed (p < 0.05). Additionally, GrimAA was linked to lower global cognition scores (p < 0.001), independent of covariates. MR analysis suggested a potential link, showing that genetically predicted GrimAA was nominally associated with slower processing speed (p = 0.05). These findings suggest that epigenetic aging, particularly GrimAA, is independently associated with lower cognitive function in midlife and may play an important role in cognitive impairment, especially in processing speed.

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Research summary

The paper claims that epigenetic age acceleration, particularly GrimAA, is independently associated with lower cognitive function in midlife. This research is relevant as it explores the relationship between epigenetic aging and cognitive function, addressing potential underlying mechanisms of aging that could inform strategies for longevity and age-related cognitive decline.

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