Larsen 2012 Acta Physiol (Oxf)

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Larsen S, Hey-Mogensen M, Raboel R, Stride N, Helge JW, Dela F (2012) The influence of age and aerobic fitness: Effects on mitochondrial respiration in skeletal muscle. Acta Physiol (Oxf) 205:423-32.

Β» PMID:22212519

Larsen S, Hey-Mogensen M, Raboel R, Stride N, Helge JW, Dela F (2012) Acta Physiol (Oxf)

Abstract: AIM: Mitochondrial function has previously been studied in ageing, but never in humans matched for maximal oxygen uptake (VΒ·O2max). Furthermore, the influence of ageing on mitochondrial substrate sensitivity is not known.

METHODS: Skeletal muscle mitochondrial respiratory capacity and mitochondrial substrate sensitivity was measured by respirometry in young (23Β±3 years) and middle-aged (53Β±3 years) male subjects with similar VΒ·O2max. Protocols for respirometry included titration of substrates for complexI (glutamate), complexII (succinate) and both (octanoyl-carnitine) for calculation of substrate sensitivity (C(50) ). Myosin Heavy Chain (MHC) isoforms, citrate synthase (CS) and Ξ²-hydroxy-acyl-CoA-dehydrogenase (HAD) activity, mitochondrial DNA (mtDNA) content, protein levels of complexes I-V and antioxidant defense system (manganese superoxide dismutase (MnSOD)) was measured.

RESULTS: No differences were found in maximal mitochondrial respiration or C(50) with glutamate (2.0Β±0.3 and 1.8Β±0.3 mmol/l), succinate (3.7Β±0.2 and 3.8Β±0.4 mmol/l) or octanoyl-carnitine (47Β±8 and 56Β±7 ΞΌmol/l) in young and middle-aged subjects, respectively. Normalising 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 VΒ·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 VΒ·O2max middle-aged seems to require a higher mitochondrial content than young subjects.

β€’ O2k-Network Lab: DK Copenhagen Dela F, DK Copenhagen Larsen S

Labels: Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Skeletal muscle 

Enzyme: Complex I, Complex II;succinate dehydrogenase  Regulation: Substrate 

HRR: Oxygraph-2k 

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