Epigenetic age acceleration tracks lower baseline cognition and greater retest gains
In middle-aged adults, biological aging correlated with processing speed variability and baseline performance but did not predict cognitive change over time.
In a study of 139 adults aged 25 to 65, researchers investigated how DNA methylation measures of biological age relate to specific patterns of cognitive function. Using four annual high-frequency assessment bursts, the team evaluated working memory and processing speed via N-Back and Symbol Search tasks. They measured biological age deviation using clocks including Horvath, Hannum, PhenoAge, GrimAge, SystemsAge, and DunedinPACE. Participants with greater epigenetic age deviation, faster DunedinPACE, and older chronological age exhibited lower baseline peak performance. Biologically older participants also displayed higher intraindividual variability in processing speed and greater retest-related gains within and across testing bursts. However, neither biological age deviation nor chronological age predicted cognitive change over time. Greater chronological age alone linked to more forgetting between bursts.
Why it matters
The findings show that epigenetic clocks capture distinct features of cognitive performance, such as baseline ability and short-term retest gains, during early and middle adulthood. This underscores the utility of multidimensional testing to uncover subtle functional differences linked to biological aging.
Caveats
The study was observational and limited by a modest sample size of 139 participants spanning young adulthood to early old age.
- Epigenetic alterations
- DNA methylation
- DunedinPACE
- GrimAge
- Hannum
- Horvath1
- Horvath2
- PhenoAge
- SystemsAge
- Homo sapiens
The paper
Exploring Epigenetic Aging and Cognitive Change in Middle Adulthood
Zavala DV, Kim SH, Felt JM et al.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences · 26 Sep 2026