Senescence marker p16INK4a expression in patients with multiple sclerosis

Abstract

ObjectivesTelomere attrition is associated with disability accumulation and brain atrophy in multiple sclerosis (MS). Downstream of telomere attrition is cellular senescence. We sought to determine differences in the cellular senescence marker p16INK4a expression between MS and healthy control participants and the association of p16INK4a expression with MS disability and treatment exposure. MethodsPatients meeting diagnostic criteria for MS and healthy controls were recruited for a cross-sectional pilot study. RNA was extracted from peripheral blood mononuclear cells (PBMCs) and p16INK4a expression levels were measured using qRT PCR. Spearman correlation coefficients and regression models were applied to compare expression levels to chronological age, assess case control differences, and determine associations with clinical outcome measures. ResultsFifty-two participants with MS (67 % female, ages 25–70) and 38 healthy controls (66 % female, ages 23–65) were included. p16INK4a levels were not linearly correlated with chronological age in MS (rhos = −0.01, p = 0.94) or control participants (rhos = 0.02, p = 0.92). Higher median p16INK4a levels were observed in the >50-year age group for MS (0.25, IQR 0.14–0.35) vs. controls (0.12, IQR 0.05–0.15) and in this age group B cell depletion therapy was associated with lower expression levels. p16INK4a expression was not associated with any of the measured MS disability outcomes. DiscussionCaution is needed with using p16INK4a expression level from PBMCs as an aging biomarker in MS participants, given lack of correlation with chronological age or large associations with clinical outcomes.