Epigenetic age acceleration and cognitive function in African American adults in Midlife: The atherosclerosis risk in communities study

Jan Bressler, Riccardo E. Marioni, Rosie M. Walker, Rui Xia, Rebecca F. Gottesman, B. Gwen Windham, Megan L. Grove, Weihua Guan, James S. Pankow, Kathryn L. Evans, Andrew M. McIntosh, Ian J. Deary, Thomas H. Mosley, Eric Boerwinkle, Myriam Fornage

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual's chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47-70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (β = -0.140 words; p =. 001) and after adding other potential confounding variables (β = -0.104 words, p =. 023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: β = -0.199 words; p =. 034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: β = -0.110 words, p =. 003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.

Original languageEnglish (US)
Pages (from-to)473-480
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number3
StatePublished - Feb 14 2020

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke, National Institutes of Health grant number 5R01NS087541. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I). Funding was also supported by National Heart, Lung, and Blood Institute, National Institutes of Health grant number 5RC2HL102419. Generation Scotland: the Scottish Family Health Study received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” [STRADL] Reference 104036/Z/14/Z). AMM acknowledges the support of the Dr. Mortimer and Theresa Sackler Foundation. REM is supported by Alzheimer’s Research UK major project grant ARUK-PG2017B-10.

Publisher Copyright:
© 2019 The Author(s) 2019.


  • DNA methylation age
  • Epigenetic age
  • Neuropsychological tests
  • Verbal fluency


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