Kular Lara, Klose Dennis, Urdánoz-Casado Amaya, Ewing Ewoud, Planell Nuria, Gomez-Cabrero David, Needhamsen Maria, Jagodic Maja
Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Neuroepigenetics Laboratory, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, Pamplona, Spain.
Front Aging Neurosci. 2022 Aug 24;14:926468. doi: 10.3389/fnagi.2022.926468. eCollection 2022.
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.
We applied Horvath's multi-tissue and Shireby's brain-specific Cortical clock on bulk brain tissue ( = 46), sorted neuronal ( = 54), and glial nuclei ( = 66) from post-mortem brain tissue of progressive MS patients and controls.
We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls ( = 0.0024) using the Cortical clock, which held after adjustment for covariates ( = 0.0263). The 4.8-year age acceleration found in MS neurons ( = 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.
While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性神经退行性疾病，其特征是在疾病后期进展阶段会出现不可逆的残疾。越来越多的证据表明，疾病进展取决于年龄和中枢神经系统内的炎症。我们旨在使用基于DNA甲基化的表观遗传时钟，研究MS患者大脑组织和分选细胞核中的表观遗传衰老情况。
我们将Horvath的多组织时钟和Shireby的大脑特异性皮质时钟应用于来自进展型MS患者和对照组的死后脑组织的大脑组织整体样本（n = 46）、分选的神经元核（n = 54）和神经胶质细胞核（n = 66）。
使用皮质时钟，我们发现与对照组相比，MS患者的神经胶质细胞中年龄加速残差显著增加，相当于3.6岁（P = 0.0024），在对协变量进行调整后该结果依然成立（P = 0.0263）。在MS神经元中发现的4.8岁年龄加速（P = 0.0054）在对协变量进行调整后不成立，并且在MS患者和对照组之间的大脑组织整体样本中未观察到年龄加速残差的显著差异。
虽然这些发现需要在更大的队列中进行重复验证，但我们的研究表明，进展型MS患者的神经胶质细胞表现出加速的生物衰老。
