Department of Biomedical Sciences, University of Lausanne, CH-1015, Lausanne, Switzerland; Institute of Sport Sciences, University of Lausanne, CH-1015, Lausanne, Switzerland.
Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Ageing Res Rev. 2021 Jul;68:101343. doi: 10.1016/j.arr.2021.101343. Epub 2021 Apr 15.
The absolute reliance of the mammalian brain on oxygen to generate ATP renders it acutely vulnerable to hypoxia, whether at high altitude or in clinical settings of anemia or pulmonary disease. Hypoxia is pivotal to the pathogeneses of myriad neurological disorders, including Alzheimer's, Parkinson's and other age-related neurodegenerative diseases. Conversely, reduced environmental oxygen, e.g. sojourns or residing at high altitudes, may impart favorable effects on aging and mortality. Moreover, controlled hypoxia exposure may represent a treatment strategy for age-related neurological disorders. This review discusses evidence of hypoxia's beneficial vs. detrimental impacts on the aging brain and the molecular mechanisms that mediate these divergent effects. It draws upon an extensive literature search on the effects of hypoxia/altitude on brain aging, and detailed analysis of all identified studies directly comparing brain responses to hypoxia in young vs. aged humans or rodents. Special attention is directed toward the risks vs. benefits of hypoxia exposure to the elderly, and potential therapeutic applications of hypoxia for neurodegenerative diseases. Finally, important questions for future research are discussed.
哺乳动物的大脑完全依赖氧气来产生 ATP，这使其极易受到缺氧的影响，无论是在高海拔地区还是在贫血或肺部疾病的临床环境中。缺氧是包括阿尔茨海默病、帕金森病和其他与年龄相关的神经退行性疾病在内的无数神经疾病发病机制的关键。相反，环境氧气减少，例如在高海拔地区逗留或居住，可能对衰老和死亡率产生有利影响。此外，控制缺氧暴露可能代表一种治疗与年龄相关的神经退行性疾病的策略。本综述讨论了缺氧对衰老大脑的有益和有害影响的证据，以及介导这些不同影响的分子机制。它借鉴了关于缺氧/海拔对大脑衰老影响的广泛文献检索，并详细分析了所有直接比较年轻人和老年人或啮齿动物对缺氧反应的已确定研究。特别关注缺氧暴露对老年人的风险与益处，以及缺氧对神经退行性疾病的潜在治疗应用。最后，讨论了未来研究的重要问题。
