What telomeres teach us about MS

Abstract

While the precise mechanisms driving progressive forms of MS are not fully understood, patient age has clear impact on disease phenotype. The very young with MS have high relapse rates and virtually no progressive disease, whereas older patients tend to experience more rapid disability accumulation with few relapses. Defining a patient's biological age may offer more precision in determining the role of aging processes in MS phenotype and pathophysiology than just working with an individual's birthdate. The most well recognized measurement of an individual's "biological clock" is telomere length (TL). While TL may differ across tissue types in an individual, most cells TL correlate well with leukocyte TL (LTL), which is the most common biomarker used for aging. LTL has been associated with risk for aging related diseases and most recently with higher levels of disability and brain atrophy in people living with MS. LTL explains 15% of the overall association of chronological age with MS disability level. While LTL may be used just as a biomarker of overall somatic aging processes, triggering of the DNA damage response by telomere attrition leads to senescence pathways that are likely highly relevant to a chronic autoimmune disease. Considering reproductive aging factors, particularly ovarian aging in women, which correlates with LTL and oocyte telomere length, may complement measurements of somatic aging in understanding MS progression. The key to stopping non-relapse related progression in MS might lie in targeting pathways related to biological aging effects on the immune and nervous systems.