Fan Haixia, Zhang Minheng, Wen Jie, Wang Shengyuan, Yuan Minghao, Sun Houchao, Shu Liu, Yang Xu, Pu Yinshuang, Cai Zhiyou
Chongqing Medical University, Chongqing 400042, China.
Department of Neurology, Chongqing General Hospital, Chongqing 400013, China.
J Biomed Res. 2024 Feb 26;38(2):122-136. doi: 10.7555/JBR.37.20220220.
Aging is characterized by progressive degeneration of tissues and organs, and it is positively associated with an increased mortality rate. The brain, as one of the most significantly affected organs, experiences age-related changes, including abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function, and increased levels of reactive oxygen species. These changes collectively contribute to cognitive deterioration. Aging is also a key risk factor for neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. For many years, neurodegenerative disease investigations have primarily focused on neurons, with less attention given to microglial cells. However, recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the perspective of the microglia. In doing so, we present the current knowledge on the correlation between brain aging and the microglia, summarize recent progress of investigations about the microglia in normal aging, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and then discuss the correlation between the senescent microglia and the brain, which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.
衰老的特征是组织和器官的渐进性退化，并且与死亡率增加呈正相关。大脑作为受影响最显著的器官之一，会经历与年龄相关的变化，包括异常的神经元活动、功能失调的钙稳态、失调的线粒体功能以及活性氧水平升高。这些变化共同导致认知能力下降。衰老也是神经退行性疾病的关键风险因素，如阿尔茨海默病和帕金森病。多年来，神经退行性疾病的研究主要集中在神经元上，对小胶质细胞的关注较少。然而，最近，小胶质细胞稳态已成为神经疾病发病机制中的重要调节因子。在此，我们从小胶质细胞的角度对大脑衰老进行概述。这样做时，我们展示了关于大脑衰老与小胶质细胞之间相关性的当前知识，总结了关于正常衰老、阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症中小胶质细胞研究的最新进展，然后讨论衰老小胶质细胞与大脑之间的相关性，最后将呈现大脑衰老过程中小胶质细胞所涉及的分子复杂性，并给出健康衰老的建议。
