Lesnefsky Edward J, Hoppel Charles L
Department of Medicine, Division of Cardiology, Case Western Reserve University, Cleveland, OH, USA.
Ageing Res Rev. 2006 Nov;5(4):402-33. doi: 10.1016/j.arr.2006.04.001. Epub 2006 Jul 10.
This review addresses the data that support the presence and contribution of decreased mitochondrial oxidative phosphorylation during aging to impaired cellular metabolism. Aging impairs substrate oxidation, decreases cellular energy production and increases the production of reactive intermediates that are toxic to the cell. First, the basic principles of mitochondrial oxidative physiology are briefly reviewed. Second, the focus on the relationship of altered mitochondrial respiration to the increased production of reactive oxygen species that are employed by the "rate of living" and the "uncoupling to survive" theories of aging are discussed. Third, the impairment of function of respiration in aging is reviewed using an organ-based approach in mammalian systems. Fourth, the current state of knowledge regarding aging-induced alterations in the composition and function of key mitochondrial constituents is addressed. Model organisms, including C. elegans and D. melanogaster are included where pertinent. Fifth, these defects are related to knowledge regarding the production of reactive oxygen species from specific sites of the electron transport chain.
本综述阐述了支持衰老过程中线粒体氧化磷酸化降低对细胞代谢受损的存在及作用的数据。衰老会损害底物氧化，降低细胞能量产生，并增加对细胞有毒的反应性中间体的产生。首先，简要回顾线粒体氧化生理学的基本原理。其次，讨论线粒体呼吸改变与衰老的“生存速率”和“解偶联以生存”理论所采用的活性氧增加产生之间的关系。第三，在哺乳动物系统中采用基于器官的方法回顾衰老过程中呼吸功能的损害。第四，阐述关于衰老诱导关键线粒体成分的组成和功能改变的当前知识状态。相关情况下会纳入包括秀丽隐杆线虫和黑腹果蝇在内的模式生物。第五，这些缺陷与关于电子传递链特定部位活性氧产生的知识相关。
