Age-associated changes in mitochondrial mRNA expression and translation in the Wistar rat heart.
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 the 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.
Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, MD 21224, USA.
E K
EK
Hudson
N
N
Tsuchiya
R G
RG
Hansford
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003576:Electron Transport Complex IV / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D003576:Electron Transport Complex IV