Much evidence now suggests that superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) may be a major intracellular protective enzyme against oxygen toxicity by catalyzing the removal of the superoxide radical. We examined the possible role this enzyme may have in determining the life-span of primate species. Superoxide dismutase specific activity levels were measured in cytoplasmic fractions of liver, brain, and heart of 2 rodent and 12 primate species. These species had maximum life-span potentials ranging from 3.5 to 95 years. Liver, brain, and heart had similar specific activity levels for a given species, but the levels for different species varied over 2-fold, with man having the highest level.No general correlation was found in the levels with life-span.However, the ratio of superoxide dismutase specific activity to specific metabolic rate of the tissue or of the whole adult organism was found to increase with increasing maximum lifespan potential for all the species. This correlation suggests that longer-lived species have a higher degree of protection against by-products of oxygen metabolism.A wide range exists in maximum life-span potential (MLP) of different mammalian species which may be the result of relatively small biological differences (1-3). Much of the evolution of mammalian species may have been the result of alterations in the temporal and quantitative expression of a conserved set of structural genes (4-6). Consistent with this view is the high rate of increase in MLP during the evolution of the primates, particularly along the hominid ancestral-descendant sequence (7). This high rate implies that relatively few genetic alterations may have been necessary to substantially prolong the period of general health maintenance (8, 9). These and other data have suggested that, as in the evolution of morphology and other characteristics of a species, modifications in gene regulation may be involved in the evolution of longevity or health maintenance (7, 10).We are testing this hypothesis by searching for a correlation between the level of expression of potentially important genetic repair and protective processes and the MLP of mammalian species. There is compelling evidence that superoxide dismutase (SODase; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a major protective enzyme against oxygen toxicity, which acts by catalyzing the removal of the superoxide radical (11-13). In this paper we show the relative level of SODase specific activity as a function of MLP in liver, brain, and heart for 2 rodent and 12 primate species. Results indicate an excellent positive correlation between the ratio of SODase specific activity to specific metabolic rate (SMR) and MLP for these species. MATERIALS AND METHODS