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Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers
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Summary: Mitochondria regulate cellular bioenergetics and apoptosis and have been implicated in aging. However, it remains unclear whether age‐related loss of muscle mass, known as sarcopenia, is associated with abnormal mitochondrial function. Two technically different approaches have mainly been used to measure mitochondrial function: isolated mitochondria and permeabilized myofiber bundles, but the reliability of these measures in the context of sarcopenia has not been systematically assessed before. A key difference between these approaches is that contrary to isolated mitochondria, permeabilized bundles contain the totality of fiber mitochondria where normal mitochondrial morphology and intracellular interactions are preserved. Using the gastrocnemius muscle from young adult and senescent rats, we show marked effects of aging on three primary indices of mitochondrial function (respiration, H 2 O 2 emission, sensitivity of permeability transition pore to Ca 2+ ) when measured in isolated mitochondria, but to a much lesser degree when measured in permeabilized bundles. Our results clearly demonstrate that mitochondrial isolation procedures typically employed to study aged muscles expose functional impairments not seen in situ . We conclude that aging is associated with more modest changes in mitochondrial function in sarcopenic muscle than suggested previously from isolated organelle studies.
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“Furthermore, several of these investigations were performed in isolated mitochondria (6,9,11), which has been shown to exaggerate the observed deficit in mitochondrial function, when compared to measurements conducted on permeabilized myofibers (17).”
From Chronological Age Does not Influence Ex-vivo Mitochondrial Respiration and Quality Control in Skeletal Muscle (2016) · cites this paper as [17]
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RetractedThe mitochondrial permeability transition
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Self-citationMitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing
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Metadata
- Authors
- Picard, M., Ritchie, D., Wright, K. J., Romestaing, C., Thomas, M. M., Rowan, S. L., Taivassalo, T., & Hepple, R. T.
- Affiliations
- McGill University (CA)
- University of Calgary (CA)
- Université de Lyon (FR)
- Corresponding author
- Hepple, Russell T.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-11-10
- Volume
- 9
- Issue
- 6
- Pages
- 1032-1046
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1600619258
- Cited by
- 238
- References
- 72
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 20 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 12 · 2019: 12 · 2018: 25 · 2017: 19 · 2016: 17 · 2015: 9 · 2014: 10 · 2013: 25 · 2012: 16
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- University of Calgary
- Directorate for Biological Sciences
- Canadian Institutes of Health Research (84673_1, MOP57808)
- 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 (medical) › Adipose Tissue and Metabolism
- Keywords
- mitochondrial function, aging, sarcopenia, isolated mitochondria, mitochondrial respiration, hydrogen peroxide emission, mitochondrial permeability transition pore, calcium sensitivity, gastrocnemius
- MeSH terms
- Aging, Animals, Calcium, Hydrogen Peroxide, Male, Mitochondria, Mitochondria, Muscle, Permeability, Rats, Inbred F344, Rats, Inbred Strains, Reactive Oxygen Species, Mitochondrial Membrane Transport Proteins, Rats
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