AGE-DEPENDENT IMPAIRMENT OF MITOCHONDRIAL-FUNCTION IN PRIMATE BRAIN

It has been hypothesized that some of the functional impairments assoc iated with aging are the result of increasing oxidative damage to mito chondrial DNA that produces defects in oxidative phosphorylation. To t est this hypothesis, we examined the enzymes that catalyze oxidative p hosphorylation in crude mitochondrial preparations from frontoparietal cortex of 20 rhesus monkeys (5-34 years old). Samples were assayed fo r complex I, complex II-III, complex IV, complex V, and citrate syntha se activities. When enzyme activities were corrected for citrate synth ase activities (to account for variable degrees of mitochondrial enric hment), linear regression analysis demonstrated a significant negative correlation of the activities of complex I (p < 0.002) and complex IV (p < 0.03) with age but no significant change in complex II-III or co mplex V activities. Relative to animals 6.9 +/- 0.9 years old (n = 7), the citrate synthase-corrected activity of complex I was reduced by 1 7% in animals 22.5 +/- 0.9 years old (n = 6) (p < 0.05) and by 22% in animals 30.7 +/- 0.9 years old (n = 7) (p < 0.01). Similar age-related reductions in the activities of complexes I and IV were obtained when enzyme activities were corrected for complex II-III activity. These f indings show an age-associated progressive impairment of mitochondrial complex I and complex IV activities in cerebral cortices of primates.