Relationship between antioxidants, prooxidants, and the aging process.

It is argued that reduced oxygen species may be one of the causal factors underlying the aging process. Experimental studies strongly support the view that the rate of metabolism is inversely associated with the rate of aging. It is pointed out that Pearl's rate of living theory is widely misunderstood, because of the mistaken belief that it advocates a fixed metabolic potential for different species or genotypes within a species. The in vivo level of oxidative stress tends to increase with age in insects and mammals as indicated by increased exhalation of alkanes. A search for the causes of this increase revealed that an age-associated decline in antioxidant defenses is neither widespread nor very impressive in magnitude. A comparison of antioxidant defenses (activities of SOD, catalase, and glutathione) in six different mammalian species did not suggest a clear association between these defenses and maximum life span potential of the species. In contrast, mitochondrial rates of O2- and H2O2 were found to increase with age in insects and mammals, and the MLSP of six mammals was found to be inversely correlated with liver mitochondrial rates of O2- and H2O2 generation. It seems that the age-related increase in oxidative stress is mainly due to the enhanced rate of O2- and H2O2 generation. It is hypothesized that variations in the rates of aging in different species, that are otherwise closely related phylogenetically, may be in part due to differences in rates of O2- and H2O2 production. Overall, the rates of oxidant generation are a better correlate of the rates of aging than are the levels of antioxidant defenses.