The following is a summary of “Evaluation of Cell-Specific Epigenetic Age Acceleration in People With Multiple Sclerosis,” published in the August 2023 issue of Neurology by Maltby et al.
Epigenetic Age Evaluation in Multiple Sclerosis (MS) – Exploring Immunosenescence and Disease Progression Driven by DNA Methylation (DNAm) Variations Among Lymphocyte Subtypes and its Link to Morbidities. Researchers performed a retrospective study to assess cell-specific epigenetic age acceleration (EAA) in individuals with MS.
They conducted a case-control analysis of EAA using pre-existing DNAm data from multiple studies. Data included Illumina 450K/EPIC arrays for MS cases and age/sex-matched controls within the same study. Multi-factor statistical modeling was employed to evaluate the primary EAA outcome. Examining EAA’s link to MS, this incorporated interaction terms to identify immune cell-specific effects. Cell-sorted DNAm data from three separate datasets were utilized to validate the findings.
The results showed DNAm data from 583 cases with MS and 643 non-MS controls. GrimAge algorithm computed EAA. MS group had higher EAA than controls (∼9 months, 95%CI: 3.6-14.4), P= 0.001. Deconvolution indicated EAA links to MS via B cells (βint=1.7, 95%CI: 0.3-2.8), P= 0.002), regardless of proportions. Validation with B cell-rich data showed MS EAA rise of 5.1 years vs. controls (95%CI: 2.8-7.4, P= 5.5×10-5). T-cell data showed no MS and EAA difference. EAA related to Beta-2-microglobulin (diff = 47,546, 95%CI: 10,067-85,026; P= 7.2×10-5), and smoking pack years (diff = 8.1, 95% CI: 1.9-14.2, P= 0.002).
They concluded B cells exhibit EAA in MS, supporting the premature immune senescence hypothesis; future research should explore age-related mechanisms.