Effect of age onin vivorates of mitochondrial protein synthesis in human skeletal muscle

Abstract

A progressive decline in muscle performance in the rapidly expanding aging population is causing a dramatic increase in disability and health care costs. A decrease in muscle endurance capacity due to mitochondrial decay likely contributes to this decline in muscle performance. We developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using needle biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and function of skeletal muscle. The fractional rate of muscle mitochondrial protein synthesis in young humans (24 ؎ 1 year) was 0.081 ؎ 0.004%⅐h ؊1 , and this rate declined to 0.047 ؎ 0.005%⅐h ؊1 by middle age (54 ؎ 1 year; P < 0.01). No further decline in the rate of mitochondrial protein synthesis (0.051 ؎ 0.004%⅐h ؊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 was approximately 35% higher in the middle-aged and elderly subjects. In addition, decreasing activities of mitochondrial enzymes were observed in muscle homogenates (cytochrome c oxidase and citrate synthase) and in isolated mitochondria (citrate synthase) with increasing age, indicating declines in muscle oxidative capacity and mitochondrial function, respectively. The decrease in the rates of mitochondrial protein synthesis is likely to be responsible for this decline in muscle oxidative capacity and mitochondrial function. These changes in muscle mitochondrial protein metabolism may contribute to the age-related decline in aerobic capacity and muscle performance.

Tracers to investigate protein and amino acid metabolism in human subjects

“…3). The highest FSR were seen in mitochondrial protein and again decreased with age (Rooyackers et al 1996a), while the FSR of a cytosolic muscle protein fraction was intermediate and did not change with age (Fig. 3).…”

“…Mean values were significantly different from those for the youngest age-group (mean 24 years): *P < 0·05. Summary of data published by Rooyackers et al (1996a) and Balagopal et al (1997).…”

Lipid metabolism in the elderly

“…In general, the glycolytic capacity of skeletal muscle is maintained with age (Rogers & Evans, 1993). In contrast, the activity of enzymes involved in oxidative metabolism (eg succinate dehydrogenase; citrate synthase; cytochrome c oxidase) and b-oxidation of fatty acids (eg H 3-hydroxyacyl-CoA dehydrogenase) are reduced with age (Coggan et al, 1992a, b;Rooyackers et al, 1996). These enzymatic changes would have the net effect of decreasing fat oxidation relative to glucose oxidation and may partially explain the reduction in exercising fat oxidation observed in older individuals (Sial et al, 1996).…”

Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres

“…Although a number of previous studies have reported a reduction in the fractional synthetic rate of mixed muscle and specific myofibrillar proteins with age,3, 24, 25 these studies were performed on muscle biopsies from human subjects. Moreover, most of the biopsies were from muscles such as the quadriceps femoris and vastus lateralis that consist of a mixture of fast‐twitch and slow‐twitch fibres and until recently, it was impossible to separate the fractional synthesis rate of the various fibre types 23.…”