EFFECT OF AGE ON IN-VIVO RATES OF MITOCHONDRIAL PROTEIN-SYNTHESIS IN HUMAN SKELETAL-MUSCLE

A progressive decline in muscle performance in the rapidly expanding a ging population is causing a dramatic increase in disability and healt h care costs. A decrease in muscle endurance capacity due to mitochond rial decay likely contributes to this decline in muscle performance. W e developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using need le biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and fund-ion of skeletal muscle. The fractional rate of muscle mitochondr ial protein synthesis in young humans (24 +/- 1 year) was 0.081 +/- 0. 004%. h(-1), and this rate declined to 0.047 +/- 0.005%. h(-1) by midd le age (54 +/- 1 year; P < 0.01). No further decline in the rate of mi tochondrial protein synthesis (0.051. +/- 0.004%. h(-1)) occurred with advancing age (73 +/- 2 years). The mitochondrial synthesis rate was about 95% higher than that of mixed protein in the young, whereas it w as approximately 35% higher in the middle-aged and elderly subjects. I n addition, decreasing activities of mitochondrial enzymes were observ ed in muscle homogenates (cytochrome c oxidase and citrate synthase) a nd in isolated mitochondria (citrate synthase) with increasing age, in dicating declines in muscle oxidative capacity and mitochondrial funct ion, respectively. The decrease in the rates of mitochondrial protein synthesis is likely to be responsible For this decline in muscle oxida tive capacity and mitochondrial function. These changes in muscle mito chondrial protein metabolism may contribute to the age-related decline in aerobic capacity and muscle performance.