AGE-ASSOCIATED CHANGES IN MITOCHONDRIAL MESSENGER-RNA EXPRESSION AND TRANSLATION IN THE WISTAR RAT-HEART

The purpose of this research is to determine possible causes and mecha nisms involved in the age-associated decline in mitochondrial activity . We have focused on cytochrome c oxidase because it is comprised of b oth nuclear and mitochondrial-encoded subunits and may provide some in sight into the coordination of the two genomes. In agreement with prev ious reports, we show an approximate 30% decrease in cardiac cytochrom e c oxidase activity at 24 months compared to 6 months with no change in the activity of the nuclear encoded citrate synthase of the mitocho ndrial matrix. The rate of mitochondrial protein synthesis as shown by [S-35]methionine incorporation decreased approximately 35% in the 24- month-old rat compared to the B-month-old rat. The decrease in protein synthesis was associated with a 30-50% reduction in the levels of mos t individually radiolabeled translation products including the COX sub units and specifically, a 23% decrease in COX1 protein steady-state le vels according to Western analysis. Similarly, there was a decrease in the mRNA steady-state levels of both nuclear and mitochondrial-encode d subunits of cytochrome c oxidase. These results suggest that a numbe r of different mechanisms are involved in the age-associated decrease in heart mitochondrial activity and these are discussed. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.