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

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Abstract

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.

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Acknowledgements

We wish to express our gratitude to all of the enthusiastic volunteers, without whom this study would not have been possible. It was a most positive experience to collaborate with both the 20+ and 70+ age groups. The expert technical assistance of Ms. I-L. Føhns, H. Lauritzen, I. Kring and Mr. B. Larson is gratefully acknowledged. The study was supported by grant 504-14 from The Danish Research Foundation.

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Authors and Affiliations

  1. Department of Biochemistry, August Krogh Institute, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen, Denmark

    Ulla F. Rasmussen & Hans N. Rasmussen

  2. Institute of Exercise and Sports Sciences, University of Copenhagen, Universitetsparken 13, 2100, Copenhagen, Denmark

    Peter Krustrup

  3. Sports Medicine Research Unit and Copenhagen Muscle Research Centre, Bispebjerg Hospital, 2400, Copenhagen NV, Denmark

    Michael Kjaer

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  1. Ulla F. Rasmussen
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  4. Hans N. Rasmussen
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Correspondence to Ulla F. Rasmussen.

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Rasmussen, U.F., Krustrup, P., Kjaer, M. et al. Human skeletal muscle mitochondrial metabolism in youth and senescence: no signs of functional changes in ATP formation and mitochondrial oxidative capacity. Pflugers Arch - Eur J Physiol 446, 270–278 (2003). https://doi.org/10.1007/s00424-003-1022-2

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  • DOI: https://doi.org/10.1007/s00424-003-1022-2

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