Clocks out of sync: Increased epigenetic aging variability in multiple sclerosis

Epigenetic clocks are composite measures of DNA methylation used as markers of biological age. This study found that epigenetic age acceleration (EAA) exhibits greater variability in individuals with multiple sclerosis (MS) compared to sex- and age-matched healthy controls (HC). Specifically, the standard deviation for PhenoAge in the secondary progressive (SP) MS group was 12.7, which is 1.5 times that of controls. A likelihood ratio test confirmed a significant difference in variance across relapsing remitting (RR) MS, SPMS, and HC groups, with a p-value of 0.017. This heterogeneity suggests future epigenetic aging studies in MS will require larger sample sizes and underscore the need for variance-aware sample size planning.