Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi, India.
Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi, India.
Mech Ageing Dev. 2022 Jun;204:111675. doi: 10.1016/j.mad.2022.111675. Epub 2022 Apr 14.
Aging is inevitable. Along with reduced ability to maintain the homeostasis of various biological processes, aging gradually deteriorates overall health. Extensive research on the aging brain has identified cellular senescence as a critical risk factor of neurodegeneration and cognitive decline. Associations of cellular senescence with neurodegenerative diseases like Alzheimer's disease, Down syndrome, Parkinson's disease, and multiple sclerosis are evident in an extensive body of literature generated over decades of research on aging. Cellular senescence triggers neurodegeneration via a complex interplay of mechanisms including neuroinflammation, mitochondrial dysfunction, oxidative stress burden, deranged protein homeostasis, and compromised nuclear and blood-brain-barrier integrity. Thus, cellular senescence can serve as a primary therapeutic target for various neurodegenerative diseases. This review summarizes the concept of cellular senescence, its role in the aging brain, and how it mediates neurodegeneration in several neurodegenerative disorders. Further, we have also highlighted senolytic therapeutics discovered and employed to ameliorate cellular senescence-associated degenerative diseases. This review can aid in providing directions for repurposing senolytic compounds and finding more therapeutic strategies targeting cellular senescence for the management and treatment of neurodegenerative diseases.
衰老是不可避免的。随着维持各种生物过程的内稳态能力的下降，衰老逐渐损害整体健康。对衰老大脑的广泛研究已经确定细胞衰老作为神经退行性变和认知能力下降的关键风险因素。在几十年的衰老研究中产生的大量文献中，细胞衰老与阿尔茨海默病、唐氏综合征、帕金森病和多发性硬化症等神经退行性疾病之间存在关联。细胞衰老通过包括神经炎症、线粒体功能障碍、氧化应激负担、蛋白质平衡失调以及核和血脑屏障完整性受损在内的一系列复杂机制引发神经退行性变。因此，细胞衰老可以作为各种神经退行性疾病的主要治疗靶点。 本综述总结了细胞衰老的概念、它在衰老大脑中的作用以及它如何在几种神经退行性疾病中介导神经退行性变。此外，我们还强调了已发现和用于改善与细胞衰老相关的退行性疾病的衰老细胞疗法。本综述可以为重新利用衰老细胞化合物和寻找更多针对细胞衰老的治疗策略提供指导，以管理和治疗神经退行性疾病。
