The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle

Authors

  • S. Larsen,

  • M. Hey-Mogensen,

    Corresponding author
    • Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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  • R. Rabøl,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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  • N. Stride,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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  • J. W. Helge,

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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  • F. Dela

    1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Correspondence: S. Larsen, M.Sc, Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen N, Denmark.

E-mail: stelar@sund.ku.dk

Abstract

Aim:

Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake (inline image). Furthermore, the influence of ageing on mitochondrial substrate sensitivity is not known.

Methods:

Skeletal muscle mitochondrial respiratory capacity and mitochondrial substrate sensitivity were measured by respirometry in young (23 ± 3 years) and middle-aged (53 ± 3 years) male subjects with similar inline image. Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl carnitine) for calculation of substrate sensitivity (C50). Myosin heavy chain (MHC) isoforms, citrate synthase (CS) and β-hydroxy-acyl-CoA-dehydrogenase (HAD) activity, mitochondrial DNA (mtDNA) content, protein levels of complexes I–V and antioxidant defence system [manganese superoxide dismutase (MnSOD)] were measured.

Results:

No differences were found in maximal mitochondrial respiration or C50 with glutamate (2.0 ± 0.3 and 1.8 ± 0.3 mm), succinate (3.7 ± 0.2 and 3.8 ± 0.4 mm) or octanoyl carnitine (47 ± 8 and 56 ± 7 μm) in young and middle-aged subjects respectively. Normalizing mitochondrial respiration to mtDNA young subjects had a higher (< 0.05) respiratory capacity per mitochondrion compared to middle-aged subjects. HAD activity and mtDNA per mg tissue were higher in middle-aged compared to young subjects. Middle-aged had a higher MHC I isoform and a lower MHC IIX isoform content compared to young subjects.

Conclusion:

Mitochondrial substrate sensitivity is not affected by ageing. When young and middle-aged men are carefully matched for inline image, mitochondrial respiratory capacity is also similar. However, per mitochondrion respiratory capacity was lower in middle-aged compared to young subjects. Thus, when matched for inline image, middle-aged seem to require a higher mitochondrial content than young subjects.

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