Author: Vignesh Subramanian, Class of 2024

Figure 1: Increasing evidence suggests biological aging, measured by examining the extent of methylation of cells’ DNA, is a stronger predictor of diminishing cognitive abilities than chronological age. 

Title: Epigenetic Age Acceleration More Accurately Predicts Memory Decline Than Chronological Age

Age acceleration is the term used to describe the difference between an individual’s chronological age, the length of time they have been alive, and their biological age, the degree of physiological development of their cells and tissues. In epigenetic age acceleration (EAA), an individual’s biological age outpaces their actual, chronological age; their cells exhibit signs of premature dysfunction, resulting in significant disruptions in their functions and consequently diminished physical capabilities and cognitive abilities for the individual. The extent of the biological aging of one’s cells can be determined with the use of DNA methylation biomarkers, which track the modification of cells’ DNA (via the addition of methyl groups aimed at repressing transcription of specific regions with increasing age) as a measure of the epigenetic “clock” of cells’ development. 

The question of whether measures of epigenetic age predict impairment of cognitive function more accurately than one’s chronological age is one of intense interest. Researchers at Stony Brook University sought to determine whether EAA was a better indicator of a decline in memory function than individuals’ actual ages. The researchers drew blood samples from 142 randomly sampled adults aged 25–65, extracting genomic DNA from their blood plasma and screening it to determine the extent of methylation in each individual’s genome to establish their biological age against five separate metrics. The researchers then had participants complete smartphone-based ambulatory cognitive assessments several times a day that asked them to match and locate specific symbols in jumbles of letters, establishing a measure of their working memory and processing speed.

The researchers found that positive EAA – wherein biological age has outpaced chronological age – was strongly associated with both poorer mean processing speed and working memory, as well as greater inconsistency in measures of both. Participants whose cells’ DNA were established as having older epigenetic ages were found to be slower at completing the cognitive assessments, even when they were not chronologically older than other participants. Participants of older biological ages also varied more greatly in their performance on the cognitive assessments, which correlated less strongly with their chronological age. Overall, the study yielded some of the first evidence that accelerated biological aging is a stronger predictor of memory function than chronological age, paving the way for future research to examine the longitudinal implications of the former. 

Works Cited:

[1] Zavala, D. V., Dzikowski, N., Gopalan, S., Harrington, K. D., Pasquini, G., Mogle, J., Reid, K., Sliwinski, M., Graham-Engeland, J.E., Engeland, C. G., Bernard, K., Veeramah, K., Scott, S. B. (2024). Epigenetic age acceleration and chronological age: Associations with cognitive performance in daily life. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 79(1), 242. https://doi.org/10.1093/gerona/glad242

[2] Image retrieved from: Wikimedia | DNA