Mitochondrial production of pro-oxidants and cellular senescence

Abstract

Mitochondria are the major intracellular producers of O₂⁻ and H₂O₂. The level of oxidative stress in cells, as indicated by the in vivo exhalation of alkanes and the concentration of molecular products of oxy-radical reactions, increases during aging in mammals as well as insects. In this paper, we discuss the relationship between mitochondrial generaton of O₂⁻ and H₂O₂, and the aging process. The rate of mitochondrial O₂⁻ and H₂O₂ generation increases with age in houselifes and the brain, heart and liver of rat. This rate has been found to correspond to the life expectancy of flies to the maximum life span potential (MLSP) of six different mammalian species, namely, mouse, rat, guinea pig, rabbit, pig and cow. In contrast, the level of antioxidant defenses provided by activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione concentration neither uniformly declines with age nor corresponds to variations in MLSP of different mammalian species. It is argued that the rate of mitochondrial O₂⁻ and H₂O₂ generation rather than the antioxidant level may act as a longevity determinant.