Aging is characterized by a progressive muscle wasting and loss of muscle function. Quantitative and qualitative loss of skeletal muscle mitochondria may contribute to these features of the aging process. We investigated the activity of cytochrome c oxidase (COX; an indicator of mitochondrial content) and in vivo synthesis rates of mitochondrial protein in quadriceps muscle biopsies of 7 young (22±2), 8 middle aged (52±3) and 6 old (77±7) human subjects. Muscle biopsies were taken at 5 and 10 h during a primed continuous infusion of L-[l-13C]leucine. COX activities were measured in whole muscle homogenates. Subsarcolemmal mitochondria were isolated from muscle by established fractional centrifugation procedures and hydrolysed. Enrichments of the N-hepta fluorobutyryl, methyl ester of leucine were measured on an on-line gas chromatograph/combustion/isotope ratio mass spectrometer (Delta S). Fractional protein synthesis rates (FSR) were calculated from the increment of 13C-leucine enrichment in muscle mitochondrial protein using plasma 13C-ketoisocaproic acid as a surrogate of the precursor for protein synthesis. voung middjg old p f ANQVA) VO2max (ml.min-1.kg fat free mass-1) 60±8 46±8 34±8b 0.0001 COX (μU/mg protein) 139±40 119± 19 97±31 a 0.0481 FSR(%/h) 0.082±0.013 0.046±0.019 0.050±0.015' 0.0008 a significantly different from young; b: significantly different from young and middle (Tukey-Kramer). FSR of mitochondrial protein in the young subjects is approximately twice as high (2.1±0,6) as the mixed muscle protein synthesis rates (0.041±0.008 %/h) measured in the same subjects. Aging is related with a progressive loss of mitochondrial content (COX) in skeletal muscle which is the result of a substantial decline in synthesis rates of mitochondrial protein observed from middle age onwards. This might explain the decrease in VO2maxand loss of muscle function with aging.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)