MITOCHONDRIAL METABOLISM AND SUBSTRATE COMPETITION IN THE AGING FISCHER RAT-HEART

Objective: The objective was to examine mitochondrial oxidative metabo lism of long chain fatty acids and to compare it with glucose uptake a nd the generation of pressure-volume work in hearts from mature and ag ed rats. Methods: Hearts from mature (8 to 15 months of age) and old ( 28 to 30 months) Fischer 344 rats were perfused as working hearts with either 10 mM glucose or glucose plus 1 mM oleic acid (2% bovine serum albumin) and rates of glucose extraction were determined. Hearts were subjected to a stepwise increase in work load. In separate experiment s, mitochondria were isolated from mature and old rat hearts and assay ed for respiratory function, carnitine exchange, carnitine palmitoyltr ansferase activities, and phospholipid content. Results: Although ther e were no differences in peak work attained between the mature and old rats in the presence of either glucose alone or glucose plus oleic ac id, glucose utilisation was significantly decreased by oleate in the m ature animals only. No significant changes in either glutamate or succ inate (+rotenone) supported respiration were found in heart mitochondr ia isolated from old rats compared with mature animals. In agreement w ith prior studies with the Wistar rat model of aging, significant decr ements in the rates of palmitoylcarnitine oxidation and carnitine exch ange were apparent in the old Fischer animals. A significant lowering of heart mitochondrial carnitine palmitoyltransferase I activity was a lso found in the old animals. A decrease in the amounts of carnitine l oaded in mitochondria from old animals is consistent with reduced carn itine content in both mitochondria and whole hearts from aged Wistar a nd Fischer rats. A significant (23%) reduction in heart mitochondrial cardiolipin content from 30 month old Fischer rats suggests that this phospholipid may also contribute to the lower rates of carnitine and a cylcarnitine transport across the mitochondrial inner membrane. Conclu sion: The limitation in the delivery of fatty acyl units to beta oxida tion as measured in isolated heart mitochondria from old rats has a ph ysiological correlate in the intact heart. The well documented suppres sion of glucose oxidation by fatty acids seen in the adult rat heart i s not seen in old hearts, supporting the in vitro finding of decreased oxidation of palmitoylcarnitine with senescence.