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

• Published in: Acta Physiologica Vol. 205; no. 3; pp. 423 - 432
• Main Authors: Larsen, S., Hey-Mogensen, M., Rabøl, R., Stride, N., Helge, J. W., Dela, F.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.07.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - metabolism; Adult; aerobic fitness; ageing; Aging - physiology; Biological and medical sciences; Biopsy; DNA, Mitochondrial - metabolism; Electron Transport - physiology; Exercise - physiology; Fundamental and applied biological sciences. Psychology; Humans; Male; Middle Aged; Mitochondria, Muscle - physiology; mitochondrial capacity; mitochondrial substrate sensitivity; Muscle, Skeletal - pathology; Muscle, Skeletal - physiology; Myosin Heavy Chains - metabolism; Oxygen Consumption - physiology; Physical Fitness - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Senescence; Ageing; aerobic fitness; Striated muscle; mitochondrial substrate sensitivity; Vertebrata; Physical fitness; Mitochondria; Sensitivity; Mammalia; mitochondrial capacity; Respiration; Age
• ISSN: 1748-1708; 1748-1716; 1748-1716
• DOI: 10.1111/j.1748-1716.2012.02408.x

Aim: Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake (V·O2max). 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 V·O2max. 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 (P < 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 V·O2max, mitochondrial respiratory capacity is also similar. However, per mitochondrion respiratory capacity was lower in middle‐aged compared to young subjects. Thus, when matched for V·O2max, middle‐aged seem to require a higher mitochondrial content than young subjects.