Mitochondrial oxidative stress plays a key role in aging and apoptosis

Harman first suggested in 1972 that mitochondria might be the biological cl ock in aging, noting that the rate of oxygen consumption should determine t he rate of accumulation of mitochondrial damage produced by free radical re actions. Later in 1980 Miquel and coworkers proposed the mitochondrial theo ry of cell aging.,Mitochondria from postmitotic cells use O-2 at a high rat e, hence releasing oxygen radicals that exceed the cellular antioxidant def ences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported b etween the rate of mitochondrial production of hydroperoxide and the maximu m life span of species. An important change in mitochondrial lipid composit ion is the age-related decrease found in cardiolipin content, The concurren t enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitocho ndrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production o f reactive oxygen species, which in turn would aggravate the oxidative dama ge to mitochondria. Moreover, superoxide radicals produced during mitochond rial respiration react with nitric oxide inside mitochondria to yield damag ing peroxynitrite. Treatment with certain antioxidants, such as sulphur-con taining antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 76 1, protects against the age-associated oxidative damage to mtDNA and the ox idation of mitochondrial glutathione. Moreover, the EGb 761 extract also pr events changes in mitochondrial morphology and function associated with agi ng of the brain and liver.