Age-associated changes in mitochondrial mRNA expression and translation in the Wistar rat heart

Abstract

The purpose of this research is to determine possible causes and mechanisms involved in the age-associated decline in mitochondrial activity. We have focused on cytochrome c oxidase because it is comprised of both nuclear and mitochondrial-encoded subunits and may provide some insight into the coordination of the two genomes. In agreement with previous reports, we show an approximate 30% decrease in cardiac cytochrome c oxidase activity at 24 months compared to 6 months with no change in the activity of the nuclear encoded citrate synthase of the mitochondrial matrix. The rate of mitochondrial protein synthesis as shown by [ 35S]methionine incorporation decreased approximately 35% in the 24-month-old rat compared to the 6-month-old rat. The decrease in protein synthesis was associated with a 30–50% reduction in the levels of most individually radiolabeled translation products including the COX subunits and specifically, a 23% decrease in COX1 protein steady-state levels according to Western analysis. Similarly, there was a decrease in the mRNA steady-state levels of both nuclear and mitochondrial-encoded subunits of cytochrome c oxidase. These results suggest that a number of different mechanisms are involved in the age-associated decrease in heart mitochondrial activity and these are discussed.