REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE--CENTRAL NERVOUS SYSTEM

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This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise survival of neurones. We have examined the possibility that impaired mitochondrial protein synthesis may result in decreased respiratory chain function in old age. The respiratory chain complexes chosen for study are those in which one or more subunit is coded for by mT-DNA; viz, NADH-CoQ oxidoreductase (Complex 1); cytochrome c oxidase (Complex IV); F1-Fo-ATPase (Complex V). In addition, State 3 (ADP- dependent) O(2)-uptake with glutamate plus malate and with succinate as substrate was studied. At this time, activities have been found to be similar in cerebral cortex, hippocampus and striatum, when young adult (6 mo) and senescent (24 mo) male rats were compared. In a collaboration with Dr. C. Filburn of LBC, we have also initiated a study of the incidence of deletions of mt-DNA in the brain regions identified above, as a function of aging.