Epigenetic age acceleration and midlife cognition: joint evidence from observational study and Mendelian randomization
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.
Authors
- Yang Pan (ORCID: https://orcid.org/0000-0003-3487-7233)
- David Alan Bennett (ORCID: https://orcid.org/0000-0003-3689-554X)
- Ana W. Capuano (ORCID: https://orcid.org/0000-0002-3505-344X)
- Zhijie Huang (ORCID: https://orcid.org/0000-0002-7312-4982)
- Changwei Li (ORCID: https://orcid.org/0000-0002-9203-304X)
- Ileana De Anda‐Duran (ORCID: https://orcid.org/0000-0003-3629-9465)
- Tanika N. Kelly (ORCID: https://orcid.org/0000-0002-7348-4451)
- Lydia Bazzano (ORCID: https://orcid.org/0000-0002-8958-1352)
- Owen Carmichael (ORCID: https://orcid.org/0000-0002-0576-0047)
- Kristine S. Yaffe (ORCID: https://orcid.org/0000-0003-0919-3825)
- Sun Xiao (ORCID: https://orcid.org/0000-0002-7012-467X)
- Jinying Zhao (ORCID: https://orcid.org/0000-0003-3243-2660)
- Wei Chen (ORCID: https://orcid.org/0000-0003-1566-7943)
- Ruiyuan Zhang (ORCID: https://orcid.org/0000-0002-4639-3300)
Institutions
- Pennington Biomedical Research Center (US)
- Tulane University (US)
- Rush University Medical Center (US)
- Illinois College (US)
- University of California, San Francisco (US)
- University of Florida (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Southwestern Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Florida College (US)
Publication Details
- Journal
- npj Aging
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1038/s41514-025-00265-6
- Citations
- 2
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Institutes of Health
- National Institute on Aging
- National Institute of General Medical Sciences