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

M Hey-Mogensen; R Rabøl; N Stride; J W Helge; F Dela; Steen Larsen

doi:10.1111/j.1748-1716.2012.02408.x

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

M Hey-Mogensen, R Rabøl, N Stride, J W Helge, F Dela, Steen Larsen

43 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Acta Physiologica (Print)
Volume	205
Issue number	3
Pages (from-to)	423-32
Number of pages	10
ISSN	1748-1708
DOIs	https://doi.org/10.1111/j.1748-1716.2012.02408.x
Publication status	Published - Jul 2012

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10.1111/j.1748-1716.2012.02408.x

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title = "The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle",

abstract = "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.",

author = "M Hey-Mogensen and R Rab{\o}l and N Stride and Helge, {J W} and F Dela and Steen Larsen",

note = "{\textcopyright} 2012 The Authors Acta Physiologica {\textcopyright} 2012 Scandinavian Physiological Society.",

year = "2012",

month = jul,

doi = "10.1111/j.1748-1716.2012.02408.x",

language = "English",

volume = "205",

pages = "423--32",

journal = "Acta Physiologica",

issn = "1748-1708",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - The influence of age and aerobic fitness

T2 - effects on mitochondrial respiration in skeletal muscle

AU - Hey-Mogensen, M

AU - Rabøl, R

AU - Stride, N

AU - Helge, J W

AU - Dela, F

AU - Larsen, Steen

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

U2 - 10.1111/j.1748-1716.2012.02408.x

DO - 10.1111/j.1748-1716.2012.02408.x

M3 - Journal article

C2 - 22212519

SN - 1748-1708

VL - 205

SP - 423

EP - 432

JO - Acta Physiologica

JF - Acta Physiologica

IS - 3

ER -

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

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