Multiple sclerosis (Houndmills, Basingstoke, England), 6 1 2025, Pages 13524585251386217 Epigenetic age and telomere length correlations in pediatric-onset multiple sclerosis. Yang JH, Race J, Sumowski P, Jacques K, Fardad S, Fair A, Hazlett A, Lin J, Yilmaz D, Aaen G, Abrams A, Benson L, Casper TC, Chitnis T, Gorman M, Lotze T, Krupp L, Mar S, Ness J, Rensel M, Rose J, Schreiner T, Tillema JM, Waldman A, Wheeler Y, Barcellos LF, Waubant E, Graves JS
Background
Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes.
Objectives
To determine the correlation between DNAm and TL aging markers.
Methods
We conducted a cross-sectional case-control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL.
Results
We analyzed biological ages in 270 participants (125 POMS, mean 15.7 years; 145 controls, mean 15.3 years). There were moderate correlations among the different DNAm clocks, but no correlations between DNAm clocks and TL in pooled analyses. In a stratified analysis, only the control group showed a modest correlation between TL and PhenoAge clock (r = 0.2, p = 0.06).
Conclusions
DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.
