Leukocyte telomere length in multiple sclerosis: relationship between disability severity and pregnancy history

Michael Zhong; Sabrina Salberg; Sandeep Sampangi; Anneke van der Walt; Helmut Butzkueven; Richelle Mychasiuk; Vilija Jokubaitis

doi:10.1016/j.msard.2024.105607

Leukocyte telomere length in multiple sclerosis: relationship between disability severity and pregnancy history

Mult Scler Relat Disord. 2024 Apr 10:86:105607. doi: 10.1016/j.msard.2024.105607. Online ahead of print.

Authors

Michael Zhong¹, Sabrina Salberg², Sandeep Sampangi², Anneke van der Walt³, Helmut Butzkueven³, Richelle Mychasiuk², Vilija Jokubaitis³

Affiliations

¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, The Alfred Hospital, Melbourne, Australia. Electronic address: michael.zhong@monash.edu.
² Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
³ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, The Alfred Hospital, Melbourne, Australia.

PMID: 38631073
DOI: 10.1016/j.msard.2024.105607

Abstract

Background: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL.

Objectives: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history.

Methods: We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction.

Results: A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87).

Conclusions: The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects.

Keywords: Aging; Multiple sclerosis; Pregnancy; Telomeres.