Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source

oxygen free radicals (ROS) of mitochondrial origin seem to be involved in a ging. Whereas in other tissues complexes I or III of the respiratory chain contain the ROS generators, in this study we find that rat liver mitochondr ia generate oxygen radicals at complexes 1, II, and III. Short-term (6 week s) caloric restriction significantly decreased H2O2 production in rat liver mitochondria. This decrease in ROS production was located at complex I bec ause it occurred with complex I-linked substrates (pyruvate/malate), but di d not reach statistical significance with the complex II-linked substrate s uccinate, The mechanism responsible for the lowered ROS production was not a decrease in oxygen consumption, Instead, the mitochondria of caloric-rest ricted animals released less ROS per unit electron flow. This was due to a decrease in the degree of reduction of the complex I generator. Furthermore , oxidative damage to mitochondrial and nuclear DNA was also decreased in t he liver by short-term caloric restriction. The results agree with the idea that caloric restriction delays aging, at least in part, by decreasing the rate of mitochondrial ROS generation and thus the rate of attack to molecu les, like DNA, highly relevant for the accumulation of age-dependent change s.