Preservation of skeletal muscle mitochondrial content in older adults: Relationship between mitochondria, fibre type and high-intensity exercise training
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Key points: Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). Following 12 weeks of high‐intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria. Mitochondrial dynamics proteins are critical for mitochondrial turnover and maintenance of mitochondrial health. High‐intensity interval training (HIT) is a potent training modality shown to upregulate mitochondrial content in young adults but little is known about the effects of HIT on mitochondrial dynamics proteins in older adults. This study investigated the abundance of protein markers for mitochondrial dynamics and mitochondrial content in older adults compared to young adults. It also investigated the adaptability of mitochondria to 12 weeks of HIT in older adults. Both older and younger adults showed a higher abundance of mitochondrial respiratory chain subunits COXIV and NDUFA9 in type I compared with type II fibres, with no difference between the older adults and young groups. In whole muscle homogenates, older adults had higher mitofusin‐2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) contents compared to the young group. Also, older adults had higher levels of Mfn2 in type II fibres compared with young adults. Following HIT in older adults, MiD49 and Mfn2 levels were not different in whole muscle and Mfn2 content decreased in type II fibres. Increases in citrate synthase activity (55%) and mitochondrial respiratory chain subunits COXIV (37%) and NDUFA9 (48%) and mitochondrial respiratory chain complexes (∼70–100%) were observed in homogenates and/or single fibres. These findings reveal (i) a similar amount of mitochondria in muscle from young and healthy older adults and (ii) a robust increase of mitochondrial content following 12 weeks of HIT exercise in older adults.
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In humans, Mfn2 expression in aged skeletal muscle is reported as decreased, similar, or higher.
“In humans, while Mfn2 expression was decreased in aged skeletal muscle in one study [60], others have reported either similar [56,58,59,61] or even higher Mfn2 content in aged skeletal muscles [61].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [61]
Mitochondrial morphology and dynamics differ across muscle fiber types.
“Other studies have also highlighted that mitochondrial morphology and dynamics differ across muscle fiber types [61,66,67].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [61]
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Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
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- Authors
- Wyckelsma, V. L., Levinger, I., McKenna, M. J., Formosa, L. E., Ryan, M. T., Petersen, A. C., Anderson, M. J., & Murphy, R. M.
- Affiliations
- La Trobe University (AU)
- Victoria University (AU)
- Monash University (AU)
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Murphy, Robyn M.
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2017-04-23
- Volume
- 595
- Issue
- 11
- Pages
- 3345-3359
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC5451733
- OpenAlex
- W2593996807
- Cited by
- 91
- References
- 43
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 12 · 2021: 16 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 2
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Heart Foundation of Australia (100040)
- La Trobe University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- mitochondrial content, mitochondrial dynamics, mitofusin 2, skeletal muscle fiber types, high-intensity interval training, aging, older adults, mitochondrial turnover, mitochondrial respiratory chain, citrate synthase, mitochondrial dysfunction, training effects, fast-twitch muscle, cytochrome c oxidase subunit IV, NDUFA9, mitochondrial protein complexes, blue native PAGE
- MeSH terms
- High-Intensity Interval Training, Aged, Aging, Electron Transport Complex IV, Female, Humans, Male, Mitochondria, Muscle, Peptide Elongation Factors, Up-Regulation, Muscle, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Electron Transport Complex I, Young Adult
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