Age-related changes in respiration coupled to phosphorylation. II. Cardiac mitochondria.

Age-related changes in mitochondrial adenine nucleotide metabolism may underlie the progressive decline in cardiac function. Oxidase activity coupled with phosphorylation, adenine nucleotide translocase (AdNT) activity, adenine nucleotide pool size and membrane lipid composition were determined using cardiac mitochondria from young (3 months), mature (12 months) and aged (24 months) Fischer 344 male rats which had been fed NIH-31 diet. While an age-associated 15% decrease in respiratory activity was not significant, AdNT activity of the aged rat was 20% lower (P less than 0.05) than that of the young rat. The exchangeable matrix adenine nucleotide pool (ATP + ADP) tended to decrease with age. In comparison to the young, membrane lipids of cardiac mitochondria from aged rat had a 43% higher (P less than 0.01) cholesterol/phospholipid-Pi ratio and a significantly lower (P less than 0.01) phosphatidyl ethanolamine/phosphatidyl choline ratio. The overall change in the fatty acid pattern of mitochondrial membrane lipids resulted in a significant (P less than 0.01) decrease in the n-6/n-3 fatty acid ratio. All values obtained for the mature rat fell between those of the young and aged rats. These data suggest that the reduced cardiac AdNT activity in the aged rat is a consequence of both a diminished pool of exchangeable adenine nucleotides and a lower AdNT velocity. Age-related changes in the lipid components of the membrane matrix in which the AdNT is embedded may underlie the decrease in respiratory activity.