Neuromuscular Disease Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Neurosci. 2020 Aug;21(8):433-444. doi: 10.1038/s41583-020-0325-z. Epub 2020 Jun 29.
Globally, 50 million people live with dementia, with Alzheimer disease (AD) being responsible for two-thirds of the total cases. As ageing is the main risk factor for dementia-related neurodegeneration, changes in the timing or nature of the cellular hallmarks of normal ageing might be key to understanding the events that convert normal ageing into neurodegeneration. Cellular senescence is a candidate mechanism that might be important for this conversion. Under persistent stress, as occurs in ageing, both postmitotic cells - including neurons - and proliferative cells - such as astrocytes and microglia, among others - can engender a state of chronic cellular senescence that is characterized by the secretion of pro-inflammatory molecules that promote the functional decline of tissues and organs. Ablation of senescent cells has been postulated as a promising therapeutic venue to target the ageing phenotype and, thus, prevent or mitigate ageing-related diseases. However, owing to a lack of evidence, it is not possible to label cellular senescence as a cause or a consequence of neurodegeneration. This Review examines cellular senescence in the context of ageing and AD, and discusses which of the processes - cellular senescence or AD - might come first.
全球有 5000 万人患有痴呆症，其中阿尔茨海默病（AD）占总病例的三分之二。由于衰老是与痴呆相关的神经退行性变的主要风险因素，因此正常衰老过程中细胞特征出现时间或性质的变化可能是理解将正常衰老转化为神经退行性变的关键。细胞衰老就是一种可能对此转化起重要作用的候选机制。在持续的压力下，如衰老时，有丝分裂后细胞 - 包括神经元 - 和增殖细胞 - 如星形胶质细胞和小胶质细胞等 - 可以产生慢性细胞衰老状态，其特征是分泌促炎分子，促进组织和器官的功能下降。消除衰老细胞被认为是一种有前途的治疗方法，可以针对衰老表型，从而预防或减轻与衰老相关的疾病。然而，由于缺乏证据，不能将细胞衰老标记为神经退行性变的原因或结果。本综述在衰老和 AD 的背景下检查了细胞衰老，并讨论了哪些过程 - 细胞衰老或 AD - 可能是首先发生的。
