Maupin Elizabeth A, Adams Katrina L
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
The Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, Indiana, USA.
J Neurochem. 2025 Jan;169(1):e16301. doi: 10.1111/jnc.16301.
Aging is the most common risk factor for Multiple Sclerosis (MS) disease progression. Cellular senescence, the irreversible state of cell cycle arrest, is the main driver of aging and has been found to accumulate prematurely in neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Cellular senescence in the central nervous system of MS patients has recently gained attention, with several studies providing evidence that demyelination induces cellular senescence, with common hallmarks of p16INK4A and p21 expression, oxidative stress, and senescence-associated secreted factors. Here we discuss the current evidence of cellular senescence in animal models of MS and different glial populations in the central nervous system, highlighting the major gaps in the field that still remain. As premature senescence in MS may exacerbate demyelination and inflammation, resulting in inhibition of myelin repair, it is critical to increase understanding of cellular senescence in vivo, the functional effects of senescence on glial cells, and the impact of removing senescent cells on remyelination and MS. This emerging field holds promise for opening new avenues of treatment for MS patients.
衰老是多发性硬化症（MS）疾病进展最常见的风险因素。细胞衰老，即细胞周期停滞的不可逆状态，是衰老的主要驱动因素，并且已发现在包括阿尔茨海默病和帕金森病在内的神经退行性疾病中会过早积累。MS患者中枢神经系统中的细胞衰老最近受到关注，多项研究提供了证据表明脱髓鞘会诱导细胞衰老，其具有p16INK4A和p21表达、氧化应激以及衰老相关分泌因子等常见特征。在此，我们讨论MS动物模型和中枢神经系统中不同神经胶质细胞群中细胞衰老的当前证据，突出该领域仍然存在的主要差距。由于MS中的过早衰老可能会加剧脱髓鞘和炎症，导致髓鞘修复受到抑制，因此加深对体内细胞衰老、衰老对神经胶质细胞的功能影响以及清除衰老细胞对髓鞘再生和MS的影响的理解至关重要。这个新兴领域有望为MS患者开辟新的治疗途径。
