Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species.

Abstract

Peroxidation reactions may cause many of the dysfunctions associated with aging. Accordingly, the 30-fold differences in aging rate among the mammalian species could be determined in part by peroxidation defense processes. This possibility was tested by measuring the spontaneous autoxidation of aerobically incubated brain and kidney tissue homogenates of 24 different mammalian species as a function of their maximum lifespan potential. Results show a statistically significant inverse correlation between both the rate of autoxidation and the amount of peroxidizable substrate with maximum lifespan potential. Kinetic analysis of the data indicates that the amount of peroxidizable substrate was the major factor determining the rate of autoxidation. For human tissues, antioxidants also appear to contribute to their unusually low sensitivity to peroxidation. These results support the hypothesis that aging may be caused in part by oxygen radicals initiating peroxidation reactions and that peroxidation defense processes are involved in governing the longevity of mammalian species.Much evidence now supports oxygen radicals as a causative factor in a number of pathologies (1-4), but their importance to aging has largely been based on circumstantial evidence (5-8). Past work in our laboratory has shown a positive correlation in the concentration of a number of different antioxidants per specific metabolic rate with the maximum lifespan potential of mammalian species. These results suggested the potential importance of antioxidants in governing aging rate. However, negative or no correlations with some antioxidants were also found (7, 9, 10). Because of the difficulties in determining the total defense these antioxidants were contributing, a method was needed to estimate the net sensitivity a tissue has against oxidative damage.Aerobically incubated tissue homogenates spontaneously undergo autoxidation (11-15). The rate and extent of this reaction depends upon factors affecting its initiation, propagation, and termination (16-19). Much evidence also indicates that the sensitivity of tissue homogenates to autoxidation in vitro reflects their normal in vivo sensitivity to similar oxidative processes (20-26). Thus, a measure of the autoxidation of aerobically incubated tissue homogenates appears to represent one means of assessing a complex array of tissue defenses against oxygen radicals that may be important in governing the aging rate of different mammalian species. MATERIALS AND METHODSSource of Tissues. Tissues were from Yerkes Regional Primate Center, Duke University Primate Facility, the Washington Regional Primate Center, and Pel-Freez Biologicals. Peromyscus maniculatus (deer mouse), Peromyscus leucopus (white-footed mouse), and Mus musculus (field mouse) were from our own animal colony.Estimation of Species Longevity. Maximum lifespan potentials (MLSPs) are from a literature survey covering over 100 zoos world-wide (27). From these data, mean ± SD values were calculated. Lifespan energy potential (LEP, kcal/g)...

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

“…In agreement with this, it was demonstrated that in long-lived mammals, the low degree of membrane fatty acid unsaturation was accompanied by a low sensitivity to in vivo and in vitro lipid peroxidation (269,272,(275)(276)(277) and a low steady-state level of lipoxidation-derived adducts in both tissue and mitochondrial proteins of skeletal muscle, heart, liver, and brain (267,268,274,277,292,307). These findings were consistent with the negative correlation between MLSP and the sensitivity to lipid autoxidation of mammalian kidney and brain homogenates that had been described some years earlier (72).…”

An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms

“…In this line, lipofuscin, often considered a hallmark of aging also shows an accumulation rate that inversely correlates with longevity (Terman and Brunk 2004). These findings were consistent with the negative correlation observed between longevity and the sensitivity to lipid autoxidation of mammalian kidney and brain homogenates (Cutler 1985).…”

Regulation of Membrane Unsaturation as Antioxidant Adaptive Mechanism in Long-lived Animal Species

“…[62] These findings were consistent with the negative correlation observed between longevity and the sensitivity to lipid autoxidation of mammalian kidney and brain homogenates. [63] Interestingly, the findings from a recent work [57] centered in offspring of long-lived individuals again seem to reinforce the association between membrane unsaturation and longevity. Thus, the fatty acid composition of erythrocyte membranes from 41 nonagenarian offspring were compared with 30 matched controls.…”