Telomere length (TL) has become increasingly linked to neurodegenerative diseases like MS, where factors such as oxidative stress and immune cell dysfunction, particularly in B cells and Tregs, play a significant role.

This study aims to investigate the association between telomere length, a marker of biological age, and disease progression in Multiple Sclerosis (MS), while also examining oxidative stress and telomerase activity in PBMCs, B cells, and Treg cells of MS patients and healthy controls.

Blood samples were collected from age matched (50 ± 5) 40 MS patients across three disability groups: low EDSS (≤3.0), mid EDSS (3.5–5.5), and high EDSS (≥6.0), along with age matched healthy controls. PBMCs were isolated using density centrifugation, and B cells and Treg cells were further separated via MACS. Telomere length was quantified by qPCR, oxidative stress was analyzed using the TBARS assay, and telomerase activity was measured via ddTRAP. Statistical analysis was conducted using ANOVA with Tukey’s post-hoc test and Bonferroni correction for multiple comparisons.

Telomere length (TL) in B cells was significantly shorter in the high EDSS group compared to the low EDSS group (p=0.0283). Treg cells in MS patients exhibited significantly shorter TL than B cells, irrespective of EDSS scores (p < 0.0001). Oxidative stress analysis in 29 MS patients revealed markedly lower OS levels compared to healthy controls (p < 0.0001), while telomerase activity in 43 MS patients was significantly higher than in PBMC’s of healthy controls (p = 0.0364).

Shorter telomere length in Treg cells and longer TL in B cells of the low EDSS group highlight immunosenescence's role in MS progression. Differences in oxidative stress among MS patient groups  suggest a link to MS-related inflammation. While increased telomerase activity indicates heightened PBMC proliferation in MS, the concurrent telomere shortening suggests other factors influence telomere dynamics, warranting further research.