Tan Xingli, Gao Naiyong
School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China.
Department of Neurology, Linyi People's Hospital, Linyi, Shandong, China.
Front Neurosci. 2025 Aug 1;19:1599492. doi: 10.3389/fnins.2025.1599492. eCollection 2025.
Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.
细胞衰老(Cellular senescence)是一种永久性细胞周期停滞的状态,被认为是衰老及包括肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)在内的与年龄相关疾病的关键促成因素。衰老的生理过程会导致多种分子和细胞表型,而ALS与衰老相关生物标志物之间存在重叠的证据表明,细胞类型特异性衰老可能是ALS的一个关键因素。在ALS患者和动物模型中已检测到衰老的小胶质细胞、星形胶质细胞和神经元。然而,尽管越来越多的证据表明细胞衰老与ALS之间存在潜在联系,但这种联系尚未最终确立。重要的是,衰老细胞如何导致ALS的神经病理生理学变化在很大程度上仍然未知。此外,抗衰老疗法越来越受欢迎,这凸显了清除衰老细胞作为治疗包括ALS在内的与年龄相关疾病的一种有前景策略的潜力。本综述概述了细胞衰老,讨论了在理解不同细胞类型的衰老如何影响ALS发病机制方面的最新进展,并探讨了抗衰老疗法在ALS治疗中的潜在作用。