H2O2 production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice: sites of free radical generation and mechanisms involved.

Birds have a maximum longevity (MLSP) much higher than mammals of similar body size in spite of their high metabolic rates. In this study, State 4 and State 3 rates of H2O2 production were lower in canary (MLSP = 24 years) and parakeet (MLSP = 21 years) than in mouse (MLSP = 3.5 years) heart mitochondria. Studies using specific inhibitors of the respiratory chain indicate that free radical generation sites at Complexes I and III are responsible for these differences. Main mechanisms lowering H2O2 production in these birds are a low rate of mitochondrial oxygen consumption in the parakeet and a low mitochondrial free radical leak in the canary. Strong increases in H2O2 production during active respiration (State 3) released by addition of ADP to pyruvate/malate-supplemented mitochondria are avoided in three species because the free radical leak decreases during the transition from State 4 to State 3 respiration. These results, together with those previously obtained in pigeons and in various mammalian species, suggest that the rate of mitochondrial free radical production correlates better with the rate of aging and the MLSP than the metabolic rate. They also suggest that a low rate of mitochondrial H2O2 production is a general characteristic of birds, animals showing very slow aging rates.