Superoxide dismutase: correlation with life-span and specific metabolic rate in primate species.

Abstract

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

Decreased expression of Cu–Zn superoxide dismutase 1 in ants with extreme lifespan

“…14; t ϭ Ϫ0.616, df ϭ 17, P ϭ 0.546, Student's t test), whereas male levels are significantly higher (665 units͞mg of protein Ϯ 36.8; t ϭ Ϫ28.7, P Ͻ 0.001, Student's t test). The similar levels of SOD1 among reproducing females of these two species are consistent with another study finding SOD1 levels similar in primates of various longevities (22,30). When considering body parts, the difference between males and queens is significant for heads and abdomens.…”

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

“…This suggests that SOD1 plays a role in relation to generation time of great apes. The trend in SOD1 activities is observed both in livers, hearts, and brains [82].…”

“…SOD1 is not only systemically important in anti-aging functions, it is also one of the most abundant proteins in most cells; thus it makes sense that selection against misfolding acts particularly on SOD1. Furthermore, mass-specific SOD1 levels are 5090% higher in brains of great apes as in rodents, and are slightly lower in monkeys than in great apes [82].…”

“…It is interesting to consider whether the inverse relationship between SOD1 and general rates of evolution has a mechanistic explanation: The ratio of the activity of SOD1 vs. the specific metabolic rate correlates remarkably with life span in a study of 12 primate and two rodent species, suggesting that long-living organisms require more protection against oxidative stress [82]: Monkeys have metabolic rates more than double that of the great apes, and rodents more than five-fold higher; at the same time, specific SOD1 activity is doubly as high in humans as in rodents and intermediate in the monkeys [82]. This suggests that SOD1 plays a role in relation to generation time of great apes.…”

Postmenopausal Health and Disease from the Perspective of Evolutionary Medicine

“…On a more molecular scale, blood levels of the free radical scavenger uric acid (Ames et al 1981) tend to be higher in primates than in most mammals (Friedman et al 1995), and are especially high in apes and humans (Wu et al 1992;Oda et al 2002). Humans and apes, to the exclusion of monkeys, also share mutations in the genes responsible for another group of free radical scavengers, the superoxide dismutases (Fukuhara et al 2002), which are more active in longer-lived primate species and are most active in human organ tissues (Tolmasoff et al 1980). In terms of DNA and fidelity in macromolecular synthesis and cellular replication, humans have higher rates of DNA repair than apes (Cortopassi and Wang 1996).…”