What question did this study set out to answer?

To assess epigenetic age acceleration variability in individuals with multiple sclerosis compared to healthy controls.

April 3, 2026Open Access

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

Key Points

To assess epigenetic age acceleration variability in individuals with multiple sclerosis compared to healthy controls.
Measured DNA methylation across different MS groups and healthy controls
Calculated standard deviation of PhenoAge
Conducted likelihood ratio tests to compare variances across groups
PhenoAge standard deviation was 12.7 in secondary progressive MS, 1.5 times that of controls
Significant variance difference observed among relapsing remitting MS, secondary progressive MS, and healthy controls (p-value 0.017)
Findings indicate the need for larger sample sizes in future epigenetic studies on MS

Abstract

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.

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