Aging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

中文翻译：

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导致大脑衰老的分子和细胞途径

衰老是神经退行性疾病等多种与年龄相关的疾病的主要危险因素。了解衰老机制的生物学对于追求大脑健康至关重要。在这方面，大脑衰老的定义是神经生理功能逐渐下降、适应性神经可塑性受损、神经元 Ca2+ 稳态失调、神经炎症以及分子和细胞器氧化修饰。许多途径导致大脑衰老，包括氧化应激增加、炎症、能量代谢紊乱（例如自噬失调）、线粒体功能障碍，以及 IGF-1、mTOR、ROS、AMPK、SIRT 和 p53 作为代谢控制的中心调节剂，将通路老化，导致神经退行性疾病。此外，热量限制（CR）、体育锻炼和精神活动可以延长寿命并增强神经系统对与年龄相关的神经退行性疾病的抵抗力。CR 的神经保护作用包括增强对 ROS 生成的保护、维持细胞 Ca2+ 稳态以及抑制细胞凋亡。关于神经生物学中大脑衰老的现代分子和细胞方法的最新证据表明，脑细胞在适应衰老和抵抗神经退行性疾病方面具有巨大的潜力。