Human skeletal muscle mitochondrial metabolism in youth and senescence: No signs of functional changes in ATP formation and mitochondrial oxidative capacity

The mitochondrial theory of ageing was tested. Isolated mitochondria from the quadriceps muscle from normal, healthy, young (age 20+ years, n=12) and elderly (70+ years, n=11) humans were studied in respiratory experiments and the data expressed as activities of the muscle. In each group, the subjects exhibited a variation of physical activity but, on average, the groups were representative for their age with maximum O₂ consumption rate of 50±9 and 34±13 ml min^-1 kg^-1 (mean±SD), respectively. Thirteen different activities were assayed, α-Glycerophosphate oxidation was lower in the 70+ group (38%, P∼0.001), as was the respiratory capacity for fatty acids (19%, P∼0.03). The remaining eleven activities, including those of the central bioenergetic reactions, were not lower in the 70+ group. Pyruvate and α-ketoglutarate dehydrogenase activities (i.e. the tricarboxylic acid cycle turnover) and the respiratory chain activity could all account for ∼14 mmol O₂ min^-1 kg^-1 muscle (37°C). The capacity for aerobic ATP synthesis was ∼35 mmol ATP min^-1 kg^-1. The mitochondrial capacities were far in excess of whole-body performance. They were related to physical activity, but not to age. The mitochondrial theory of ageing, which attributes the age-related decline of muscle performance to decreased mitochondrial function, is incompatible with these results.