The electron transport system (ETS) of the inner mitochondrial membrane is the primary site of reactive oxygen species (ROS) production and therefore the main source of oxidative stress (damage to proteins, lipids, and DNA) in the mitochondria and in the cell. Free radical superoxide anions () are generated when electrons are donated from complexes I and III of the ETS to O2 instead of the appropriate ETS subunit. 2–4% of total oxygen consumption may go toward the production of ROS instead of energy as ATP. Scavenging enzymes represent an important mitochondrial defense mechanism against oxidative stress by neutralizing within the mitochondrial matrix (superoxide dismutase; MnSOD = SOD2) and catalyzing the reduction of mitochondrial SOD2-generated H2O2 to nontoxic H2O in the mitochondria and the cell (glutathione peroxidase and catalase). Mitochondria in young muscle (a) are numerous and efficient. With age (b), muscle mitochondria become less numerous and seem to develop impaired function associated with reduced oxidative capacity. Through lifestyle changes such as exercise, and caloric restriction, and caloric restriction mimetics, we hypothesize that antioxidative enzymes are upregulated, and that most of the above impairments in aged muscle may be improved (c).
