[The modified variant of mitochondrial theory of aging]

The central postulate of mitochondrial theory of aging (MTA) says that attenuation of cellular bioenergetics is the leading cause of aging. This attenuation is attributed to the accumulation of injuries into mitochondrial DNA that are exerted by reactive oxygen species (ROS). As the ROS are generated by mitochondrial respiratory chain then vicious cycle arises. As a result the ROS amount and level of injured biopolymers increase progressively and bioenergetics fades. The central postulate is fairly convincing but the mechanism of age-dependent bioenergetics attenuation is disproved by many empirical data. The new variant of MTA is suggested in this paper. According to this both the aging and the increase in ROS level are caused by the programmed bioenergetics fade. The mechanism of age-dependent increase in ROS is as follows. Superoxide radical (O2(*-)) generating by respiratory chain is neutralized in two stages: first the enzyme superoxide dismutase transforms O2(*-) into hydrogen peroxide and then H202 is converted into water and oxygen by glutathione peroxidase (GP). The reaction catalyzing by GP is shunted by Fenton reaction that produces extremely aggressive secondary radicals. The programmed bioenergetics decline decreases GP activity, which causes elevation of H202 content and increases hydrogen peroxide flow through Fenton reaction. This leads to the increase in general ROS level and to strengthening their aggressivity. Thus, both the aging and the increase in ROS level are two consequences of programmed bioenergetics decline.