Section on DNA Repair, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Section on DNA Repair, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Ageing Res Rev. 2022 Jun;78:101636. doi: 10.1016/j.arr.2022.101636. Epub 2022 Apr 29.
Adult neurogenesis, the process by which neurons are generated in certain areas of the adult brain, declines in an age-dependent manner and is one potential target for extending cognitive healthspan. Aging is a major risk factor for neurodegenerative diseases and, as lifespans are increasing, these health challenges are becoming more prevalent. An age-associated loss in neural stem cell number and/or activity could cause this decline in brain function, so interventions that reverse aging in stem cells might increase the human cognitive healthspan. In this review, we describe the involvement of adult neurogenesis in neurodegenerative diseases and address the molecular mechanistic aspects of neurogenesis that involve some of the key aggregation-prone proteins in the brain (i.e., tau, Aβ, α-synuclein, …). We summarize the research pertaining to interventions that increase neurogenesis and regulate known targets in aging research, such as mTOR and sirtuins. Lastly, we share our outlook on restoring the levels of neurogenesis to physiological levels in elderly individuals and those with neurodegeneration. We suggest that modulating neurogenesis represents a potential target for interventions that could help in the fight against neurodegeneration and cognitive decline.
成人神经发生，即在成人大脑的某些区域产生神经元的过程，会随着年龄的增长而呈下降趋势，是延长认知健康期的一个潜在目标。衰老是神经退行性疾病的一个主要危险因素，随着寿命的延长，这些健康挑战变得更加普遍。神经干细胞数量和/或活性的与年龄相关的损失可能导致大脑功能的这种下降，因此逆转干细胞衰老的干预措施可能会增加人类认知健康期。在这篇综述中，我们描述了成人神经发生在神经退行性疾病中的作用，并探讨了涉及大脑中一些关键聚集倾向蛋白（即 tau、Aβ、α-突触核蛋白等）的神经发生的分子机制方面。我们总结了与增加神经发生和调节衰老研究中已知靶点（如 mTOR 和 sirtuins）相关的研究。最后，我们分享了我们对恢复老年个体和神经退行性变个体中神经发生水平的展望。我们认为，调节神经发生代表了一种潜在的干预目标，有助于对抗神经退行性变和认知能力下降。
