Journal
FRONTIERS IN AGING NEUROSCIENCE
Volume 14, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2022.926468
Keywords
multiple sclerosis; DNA methylation; aging; epigenetic clock; brain; glial cells; neurons
Categories
Funding
- Swedish Research Council [818170]
- Swedish Association for Persons with Neurological Disabilities
- Swedish Brain Foundation
- Swedish MS Foundation
- Stockholm County Council - ALF project
- European Union [2018-05973]
- European Research Council (ERC) [733161]
- Knut and Alice Wallenberg Foundation
- Ake Wilberg Foundation
- Karolinska Institute
- Margaretha af Ugglas Foundation
- Erasmus fellowship
- Government of Navarra
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The study investigated epigenetic aging in bulk brain tissue and sorted nuclei from MS patients, revealing accelerated biological aging in glial cells of progressive MS patients compared to controls. The findings suggest a potential role of epigenetic clocks in understanding disease progression in multiple sclerosis.
BackgroundMultiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks. MethodsWe applied Horvath's multi-tissue and Shireby's brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls. ResultsWe found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (P-adj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls. ConclusionWhile the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
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