Department of Biochemistry and Molecular Biology.
Department of Pediatric and Adolescent Medicine, and.
J Clin Invest. 2018 Apr 2;128(4):1208-1216. doi: 10.1172/JCI95145. Epub 2018 Feb 19.
Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed. Numerous recent studies have demonstrated that senescent cells, which are characterized by sustained cell cycle arrest and production of a distinct senescence-associated secretory phenotype, accumulate with age and at sites of age-related diseases throughout the body, where they actively promote tissue deterioration. Cells with features of senescence have been detected in the context of brain aging and neurodegenerative disease, suggesting that they may also promote dysfunction. Here, we discuss the evidence implicating senescent cells in neurodegenerative diseases, the mechanistic contribution of these cells that may actively drive neurodegeneration, and how these cells or their effects may be targeted therapeutically.
随着整体健康状况的普遍下降，大多数慢性退行性人类疾病本质上都与年龄的增长有关。与年龄相关的认知障碍和神经退行性疾病，如帕金森病和阿尔茨海默病，是潜在的使人衰弱的疾病，缺乏有效的治疗选择，给经济和社会带来巨大的负担。大多数备受瞩目的神经退行性疾病的临床试验都导致了无效的结果，这表明需要新的方法来治疗这些病变。最近有许多研究表明，衰老细胞（其特征是持续的细胞周期停滞和产生独特的衰老相关分泌表型）随着年龄的增长以及在全身与年龄相关的疾病部位积累，在那里它们积极促进组织恶化。在脑老化和神经退行性疾病的背景下已经检测到具有衰老特征的细胞，这表明它们也可能促进功能障碍。在这里，我们讨论了衰老细胞与神经退行性疾病的关系的证据，这些细胞可能积极驱动神经退行性变的机制贡献，以及如何针对这些细胞或它们的作用进行治疗。
