Zenkov N K, Kozhin P M, Chechushkov A V, Kandalintseva N V, Martinovich G G, Menshchikova E V
Federal Research Center for Fundamental and Translational Medicine, 2 Timakova str., Novosibirsk 630117, Russian Federation, e-mail:
Novosibirsk State Pedagogical University, 28 Viluyskaya str., Novosibirsk 630126, Russian Federation.
Adv Gerontol. 2020;33(1):10-22.
The free-radical theory of aging, advanced more than 50 years ago by D.Harman, remains popular today. The review analyzes age-related changes in the main endogenous mechanisms of reactive oxygen species (ROS) production and antioxidant defense mechanisms. With age, ROS generation by mitochondria, peroxisomes, and NAD(P)H oxidases is enhanced, while the transcriptional activity of the important system Keap1/Nrf2/ARE maintaining redox balance decreases. In old animals, autophagy activity is also low, which removes damaged organelles and aggregated structures from cells. The age-related shift of the redox balance towards oxidative stress can cause the development of age-associated neurodegenerative, autoimmune and inflammatory pathologies.
衰老的自由基理论是50多年前由D.哈曼提出的，至今仍很流行。这篇综述分析了活性氧（ROS）产生的主要内源性机制和抗氧化防御机制中与年龄相关的变化。随着年龄的增长，线粒体、过氧化物酶体和NAD(P)H氧化酶产生的ROS会增加，而维持氧化还原平衡的重要系统Keap1/Nrf2/ARE的转录活性会降低。在老年动物中，自噬活性也很低，自噬可从细胞中清除受损的细胞器和聚集的结构。氧化还原平衡随年龄向氧化应激的转变可能导致与年龄相关的神经退行性、自身免疫性和炎症性疾病的发展。
