(Frontiers Media, 2022) Kular, Lara; Klose, Dennis; Urdánoz Casado, Amaya; Ewing, Ewoud; Planell, Nuria; Gómez-Cabrero, David; Needhamsen, Maria; Jagodic, Maja; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Multiple 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.
Methods: We 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.
Results: We 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 (Padj = 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.
Conclusion: While the findings warrant replication in larger cohorts, our
study suggests that glial cells of progressive MS patients exhibit accelerated
biological aging.
