Levine R L, Stadtman E R
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892-0812, USA.
Exp Gerontol. 2001 Sep;36(9):1495-502. doi: 10.1016/s0531-5565(01)00135-8.
Accumulating experimental evidence supports the proposal that many of the changes which occur during aging are a consequence of oxidative damage. Reactive oxygen species react with all three of the major cellular macromolecules, nucleic acids, lipids, and proteins. This minireview focuses on proteins as targets of oxidizing species during aging. Many of the reactions mediated by these oxidizing species result in the introduction of carbonyl groups into proteins. The steady-state level of carbonyl-bearing proteins increases exponentially during the last third of lifespan in animals ranging from C. elegans to man. Genetic and non-genetic manipulations which lengthen lifespan cause a decrease in the level of protein carbonyl while those which shorten lifespan increase the level. Oxidized proteins bearing carbonyl groups are generally dysfunctional, and in the last third of lifespan the content of these oxidized proteins rises to a level likely to cause substantial disruption of cellular function.
衰老过程中发生的许多变化是氧化损伤的结果。活性氧与细胞中的三大主要大分子，即核酸、脂质和蛋白质都能发生反应。这篇小型综述聚焦于衰老过程中作为氧化物质靶点的蛋白质。这些氧化物质介导的许多反应会导致蛋白质中引入羰基。从秀丽隐杆线虫到人类，在动物寿命的后三分之一时间里，含羰基蛋白质的稳态水平呈指数增长。延长寿命的基因和非基因操作会导致蛋白质羰基水平下降，而缩短寿命的操作则会使其水平升高。带有羰基的氧化蛋白质通常功能失调，在寿命的后三分之一时间里，这些氧化蛋白质的含量会上升到可能导致细胞功能严重紊乱的水平。
