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 O(2) consumption rate of 50+/-9 and 34+/-13 ml min(-1) kg(-1) (mean+/-SD), respectively. Thirteen different activities were assayed. alpha-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 alpha-ketoglutarate dehydrogenase activities (i.e. the tricarboxylic acid cycle turnover) and the respiratory chain activity could all account for ~14 mmol O(2) min(-1) kg(-1) muscle (37 degrees 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.
Department of Biochemistry, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen, Denmark. URasmussen @aki.ku.dk
Ulla F
UF
Rasmussen
Peter
P
Krustrup
Michael
M
Kjaer
Hans N
HN
Rasmussen
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D018709:Statistics, Nonparametric
D000255:Adenosine Triphosphate