Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences (BUMS), 9717853577, Birjand, Iran.
Behav Brain Funct. 2021 Jun 12;17(1):6. doi: 10.1186/s12993-021-00179-9.
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 Ca 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 Ca 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.
衰老是几种与年龄相关疾病（如神经退行性疾病）的主要风险因素。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，大脑衰老被定义为神经生理功能的逐渐下降、适应性神经可塑性受损、神经元 Ca 稳态失调、神经炎症以及氧化修饰的分子和细胞器。许多途径导致大脑衰老，包括增加的氧化应激、炎症、能量代谢紊乱，如自噬失调、线粒体功能障碍以及 IGF-1、mTOR、ROS、AMPK、SIRTs 和 p53 作为代谢控制的中心调节剂，将衰老与导致神经退行性疾病的途径联系起来。此外，热量限制（CR）、体育锻炼和脑力活动可以延长寿命并提高神经系统对与年龄相关的神经退行性疾病的抵抗力。CR 的神经保护作用涉及增加对 ROS 生成的保护、维持细胞 Ca 稳态和抑制细胞凋亡。关于神经生物学的现代分子和细胞方法对大脑衰老的最新证据表明，脑细胞具有适应衰老和抵抗神经退行性疾病的显著潜力。
