Telomere length as a biomarker in multiple sclerosis

Abstract

Background: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS).

Objective: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects.

Methods: Prospective 2-year study including two cohorts of young (18-35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay.

Results: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm³ and white matter volume 1.78 cm³.

Conclusion: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS.

Keywords: Multiple sclerosis; aging; telomere length.