Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved
Abstract
Age-related changes in mitochondrial H2O2 release (MHR) could be responsible for an increase in oxidative stress in skeletal muscle and participate in the development of sarcopenia. We compared MHR in vastus lateralis biopsies obtained from young (23.5+/-2.0 year, n=6) and elderly (67.3+/-1.5 year, n=6) healthy sedentary men. Isolated mitochondria were incubated in the presence of glutamate/malate/succinate, with or without rotenone. Muscle fat oxidative capacity, citrate synthase, complex II, complex III, and cytochrome c oxidase activities were also measured. In parallel, we analyzed in gastrocnemius of young male Wistar rats (n=6), the impact of lidocaine (local anesthetic used in humans) on mitochondrial respiration and MHR. In humans, muscle oxidative capacity was preserved with age but muscle MHR was markedly enhanced in elderly subjects compared to young adults (+175%, P<0.05). Rotenone abolished this increase, demonstrating that it was due to a free radical release during reverse electron transfer from complex II towards complex I. Lidocaine can interfere with MHR measurements (intra-muscular injection in rats) but it can be avoided by minimizing contact with muscle (small multiple subcutaneous injections in humans). Physiologic consequences of the observed increase in muscle MHR with aging remain to be determined.
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Oxidative stress is consistently detected in aged skeletal muscle and is considered to contribute to ageing-related decreases in muscle mass and function.
“Oxidative stress has been consistently detected in aged skeletal muscle and is considered to contribute to ageing‐related decreases in muscle mass and function (Yan & Sohal, 1998; Capel et al. 2005; Yarian et al. 2005; Chabi et al. 2008; Sohal & Orr, 2012; Sinha‐Hikim et al. 2013; Umanskaya et al. 2014).”
From Parkin overexpression protects from ageing‐related loss of muscle mass and strength (2019) · cites this paper as Capel et al. 2005
Correlative evidence between increased levels of 8-oxo-dG and age-related deletions in mtDNA from humans, mice, rats and houseflies has been reported.
“Correlative evidence between increased levels of 8-oxo-dG and age-related deletions in mtDNA from humans (Capel et al., 2005; Hayakawa et al., 1992; Hayakawa et al., 1991), mice (Vermulst et al., 2007), rats (Sawada and Carlson, 1987) and houseflies (Sohal and Sohal, 1991) has been reported.”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Capel et al., 2005
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- Authors
- Capel, F., Rimbert, V., Lioger, D., Diot, A., Rousset, P., Mirand, P. P., Boirie, Y., Morio, B., & Mosoni, L.
- Affiliations
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Centre de Recherche en Nutrition Humaine d'Auvergne (FR)
- Corresponding author
- Mosoni, L.
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 126
- Issue
- 4
- Pages
- 505-511
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2055709885
- Cited by
- 108
- References
- 27
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 13 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 3 · 2013: 8 · 2012: 8
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- 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 › Rehabilitation › Exercise and Physiological Responses
- Keywords
- reverse electron transfer, mitochondrial respiration, aging, vastus lateralis, skeletal muscle oxidative capacity, sarcopenia, oxidative stress, rotenone, complex II, complex I, citrate synthase, cytochrome c oxidase, gastrocnemius
- MeSH terms
- Adult, Aged, Aging, Animals, Electron Transport, Humans, Hydrogen Peroxide, Male, Mitochondria, Muscle, Rats, Wistar, Muscle, Skeletal, Rats
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