image: Figure 1. Association between dCDT scores and DNAm age acceleration in 1789 participants of the FHS. The dCDT total score includes command task composite scores and copy task composite scores. DNA methylation age acceleration was obtained by regressing DNAm age metrics on chronological age. We conducted association analysis between standardized DNAm age acceleration and the dCDT total score, adjusted for age, self−reported sex, education and cell counts. The numbers inside each cell represent the P−values of the associations. The color represents the change in dCDT scores corresponding to a one SD increase in DNAm age acceleration.
Credit: Copyright: © 2025 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“These findings highlight the potential role of DNAm in cognitive function.”
BUFFALO, NY — August 26, 2025 — A new research paper was published in Volume 17, Issue 7 of Aging (Aging-US) on July 21, 2025, titled “Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study.”
In this study, led by first author Zexu Li from the Department of Anatomy and Neurobiology at Boston University Chobanian and Avedisian School of Medicine, and corresponding author Chunyu Liu from Boston University Chobanian and Avedisian School of Medicine and Boston University School of Public Health, researchers found that individuals with signs of faster biological aging had lower scores on a digital cognitive test taken seven years later. The findings suggest that the rate at which a person ages at the molecular level may be associated with how well their brain functions as they grow older.
Using data from the Framingham Heart Study, the researchers examined the relationship between biological aging and cognitive health. They used DNA methylation (DNAm) patterns—chemical changes that occur in the DNA with aging, known as epigenetic aging—to estimate biological age acceleration, and used the digital Clock Drawing Test (dCDT) to assess cognitive performance. The dCDT is a computerized version of a traditional pen-and-paper test that evaluates memory, thinking speed, and motor control. It provides an overall score and measures performance in specific areas such as spatial reasoning and movement.
Among 1,789 participants, higher levels of epigenetic age acceleration were associated with significantly lower cognitive scores, particularly those over age 65. Of all the epigenetic aging markers examined, the DunedinPACE measure showed the strongest association with reduced brain function in both younger and older adults. Other measures, such as Horvath and PhenoAge, were associated with lower scores only in older adults. Key areas affected included motor skills and spatial reasoning.
The researchers also studied blood-based protein markers used in an aging measure called GrimAge. Two proteins, PAI1 and ADM, were closely associated with lower cognitive scores, especially in older individuals. These results suggest that declines in brain and motor functions may reflect broader aging-related changes throughout the body.
“Digital cognitive measures displayed stronger associations with most DNAm aging metrics among older compared to younger participants, likely to reflect the cumulative and nonlinear age influences on both brain health and DNAm.”
This study supports the idea that epigenetic age may be a more accurate predictor of cognitive decline than chronological age. The dCDT, which is easy to use, automated, and more precise than traditional tools, may help detect early signs of brain aging. When combined with DNAm measures, it could become a valuable part of regular health screenings.
Overall, the findings provide strong evidence that faster biological aging is associated with cognitive decline. This research may lead to better ways of identifying and monitoring brain health in aging populations.
Read the full paper: DOI: https://doi.org/10.18632/aging.206285
Corresponding author: Chunyu Liu – liuc@bu.edu
Keywords: aging, epigenetic aging, DNA methylation, cognitive function, digital Clock Drawing Test
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Journal
Aging-US
Method of Research
News article
Subject of Research
Not applicable
Article Title
Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study
Article Publication Date
21-Jul-2025
COI Statement
Dr. Au is a scientific advisor to Signant Health and Novo Nordisk. The other authors have no conflict of interest.