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 ( ). 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 . Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl carnitine) for calculation of substrate sensitivity ( C 50 ). Myosin heavy chain ( MHC ) isoforms, citrate synthase ( CS ) and β‐hydroxy‐acyl‐ C o A ‐dehydrogenase ( HAD ) activity, mitochondrial DNA (mt DNA ) content, protein levels of complexes I – V and antioxidant defence system [manganese superoxide dismutase ( M n SOD )] were measured. Results: No differences were found in maximal mitochondrial respiration or C 50 with glutamate (2.0 ± 0.3 and 1.8 ± 0.3 m m ), succinate (3.7 ± 0.2 and 3.8 ± 0.4 m m ) or octanoyl carnitine (47 ± 8 and 56 ± 7 μ m ) in young and middle‐aged subjects respectively. Normalizing mitochondrial respiration to mt DNA young subjects had a higher ( P < 0.05) respiratory capacity per mitochondrion compared to middle‐aged subjects. HAD activity and mt DNA 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 , mitochondrial respiratory capacity is also similar. However, per mitochondrion respiratory capacity was lower in middle‐aged compared to young subjects. Thus, when matched for , middle‐aged seem to require a higher mitochondrial content than young subjects.
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Several studies found no effect of age on mitochondrial oxidative capacity.
“several studies found no effect of age on mitochondrial oxidative capacity [[345], [346], [347], [348], [349]]”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [347]
In human muscle, ageing is accompanied by a higher need of mitochondria to maintain the same respiratory capacity as in young people, indicating decay in mitochondrial efficiency.
“In human muscle, ageing is accompanied by a higher need of mitochondria to maintain the same respiratory capacity as in young people indicating decay in mitochondrial efficiency (Larsen et al., 2012).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Larsen et al., 2012
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Self-citation
- Authors
- Larsen, S., Hey‐Mogensen, M., Rabøl, R., Stride, N., Helge, J. W., & Dela, F.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Hey‐Mogensen, M.
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2012-02-11
- Volume
- 205
- Issue
- 3
- Pages
- 423-432
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- OpenAlex
- W2160465777
- Cited by
- 63
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 7 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 1 · 2012: 7
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- aging, cardiorespiratory fitness, mitochondrial respiration, skeletal muscle, VO2max, myosin heavy chain isoforms, citrate synthase, beta-hydroxyacyl-CoA dehydrogenase, mitochondrial DNA content, manganese superoxide dismutase
- MeSH terms
- Adult, Aging, Biopsy, DNA, Mitochondrial, Electron Transport, Humans, Male, Middle Aged, Mitochondria, Muscle, Oxygen Consumption, Physical Fitness, 3-Hydroxyacyl CoA Dehydrogenases, Exercise, Muscle, Skeletal, Myosin Heavy Chains
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