Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle
Open accessAbstract
Our intent was to investigate the mechanisms driving the adaptive potential of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a potent stimulus for organelle biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days) to induce contractile activity of skeletal muscle in 6 and 36 mo F344XBN rats. Subsequent to chronic activity, acute stimulation (1 Hz, 5 min) in situ revealed greater fatigue resistance in both age groups. However, the improvement in endurance was significantly greater in the young, compared to the old animals. Chronic muscle use also augmented SS and IMF mitochondrial volume to a greater extent in young muscle. The molecular basis for the diminished organelle expansion in aged muscle was due, in part, to the collective attenuation of the chronic stimulation-evoked increase in regulatory proteins involved in mediating mitochondrial protein import and biogenesis. Furthermore, adaptations in mitochondrial function were also blunted in old animals. However, chronic contractile activity evoked greater reductions in mitochondrially-mediated proapoptotic signaling in aged muscle. Thus, mitochondrial plasticity is retained in aged animals, however the magnitude of the changes are less compared to young animals due to attenuated molecular processes regulating organelle biogenesis.
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Alterations in mitochondrial distribution, morphology, and function are present in atrophic muscles in aging, muscle disuse, burn injury, intensive care unit-acquired weakness, insulin resistance, chronic obstructive pulmonary disease, cancer cachexia, and different neuromuscular disorders.
“Alterations in mitochondrial distribution, morphology, and function are present in atrophic muscles in aging [148–150], muscle disuse [151, 152], burn injury [153], intensive care unit-acquired weakness [154], insulin resistance [155] chronic obstructive pulmonary disease (COPD) [156], cancer cachexia [157–159], and different neuromuscular disorders [160].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [148]
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- Authors
- Ljubicic, V., Joseph, A.-M., Adhihetty, P. J., Huang, J. H., Saleem, A., Uguccioni, G., & Hood, D. A.
- Affiliations
- York University (CA)
- Corresponding author
- Hood, David A.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2009-09-12
- Volume
- 1
- Issue
- 9
- Pages
- 818-830
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC2815739
- OpenAlex
- W178295827
- Cited by
- 98
- References
- 55
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 16 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 7
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- 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 › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial biogenesis, skeletal muscle aging, mitochondrial plasticity, subsarcolemmal mitochondria, interfibrillar mitochondria, chronic electrical stimulation, mitochondrial protein import, fatigue resistance, endurance, mitochondrial function
- MeSH terms
- Adaptation, Psychological, Aging, Animals, Electron Transport Complex IV, Electric Stimulation, Male, Mitochondria, Muscle, Muscle Contraction, Muscle Proteins, Ornithine Carbamoyltransferase, Oxygen Consumption, Rats, Inbred F344, Apoptosis, Reactive Oxygen Species, Muscle, Skeletal, Muscle Fatigue, Succinic Acid, Protein Transport, Mitochondrial Proteins, Mitochondrial Membrane Transport Proteins, Rats, Mitochondrial Size, DNA Fragmentation
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