Preservation of succinic dehydrogenase and cytochrome oxidase activity in aging rhesus monkeys

Little is known about how changes in the brain during normal aging contribute to cognitive impairments. One hypothesis holds that age-related changes in oxidative metabolism are a major factor. Cytochrome oxidase (CO) and succinic dehydrogenase (SDH) are two mitochondrial enzymes in the respiratory chain that can be measured biochemically and histochemically to assess oxidative metabolism. The purpose of this study was to determine if there are age-related changes in these two markers and whether they are related to cognitive impairment. This hypothesis was investigated in twenty rhesus monkeys (Macaca mulatta) of both sexes ranging in age from 4.4–30.4 years the approximate equivalent of humans 12 to 90 years old.; One unfixed cerebral hemisphere was dissected into anatomically defined pieces and samples of the frontal, parietal, temporal and occipital lobes were assessed biochemically for CO, SDH and citrate synthase (CS). The other unfixed hemisphere was cut on a cryostat into interrupted series of 15 μm thick sections and stained histochemically for CO and SDH activity.; Biochemical assays were examined spectrophotometrically for enzyme activity. Histochemical assays yielded stained sections that allowed specific neuroanatomically defined neocortical and limbic systems to be digitized. All sections were assessed with quantitative densitometry using calibrated standards of known enzymatic activity to yield localized measures of enzyme activity. All data were analyzed with a three way repeated measures analysis of variance for the effects of age, sex, and region.; Biochemical assays did not show significant effects of age, region or sex or significant interactions indicating that there are no global changes in either CO, SDH, or CS activity. Similarly, anatomically specific histochemical assays showed no statistically significant effects of age or sex nor any significant interactions for either CO or SDH. Finally, further analysis showed no correlation of either histochemical and biochemical measures with behavioral performance indicating that individual differences in oxidative metabolism are not associated with individual levels of age-related cognitive impairment. Together the data indicate that these measures of oxidative metabolism in the brain appear to be unaffected in normal aging and are unlikely to be a major factor in age-related cognitive decline.