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Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle
Abstract
Summary: According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain. However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high‐resolution respirometry, and ROS production was analyzed by in situ staining with the redox‐sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional mitochondria and that the level of ROS production is higher in young compared to aged muscle. Accordingly, we could not find any increase in oxidative modification of proteins in muscle from elderly donors. However, the accumulation of lipofuscin was identified as a robust marker of human muscle aging. The data support a model, where ROS‐induced molecular damage is continuously removed, preventing the accumulation of dysfunctional mitochondria despite ongoing ROS production.
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“Moreover, most studies of mitochondrial respiration have not considered important covariates such as participant physical activity levels (9), adiposity (11), and fiber type percentage, which could confound the relationship between mitochondrial capacity and age (10,12,18,19).”
From Chronological Age Does not Influence Ex-vivo Mitochondrial Respiration and Quality Control in Skeletal Muscle (2016) · cites this paper as [12]
In the citing paper
“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 [346]
In the citing paper
“several studies have observed an accumulation of lipofuscin particles in aged muscles from rodents [47] and humans [111,112], suggesting that the autophagy-lysosomal function is defective.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [111]
In the citing paper
“Interestingly, these changes were not accompanied by increased levels of oxidative stress, a finding that has also been confirmed in humans (Hutter et al., 2007).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Hutter et al., 2007
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Metadata
- Authors
- Hütter, E., Skovbro, M., Lener, B., Prats, C., Rabøl, R., Dela, F., & Jansen‐Dürr, P.
- Affiliations
- Austrian Academy of Sciences (AT)
- University of Copenhagen (DK)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2007-02-05
- Volume
- 6
- Issue
- 2
- Pages
- 245-256
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2007891985
- Cited by
- 149
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 13 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 10
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Aging Cell (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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- muscle aging, oxidative stress, reactive oxygen species, mitochondrial dysfunction, lipofuscin accumulation, skeletal muscle, mitochondrial respiration, protein oxidative modification, free radical theory of aging, vastus lateralis, mitochondrial quality control
- MeSH terms
- Adult, Aged, Aging, Biopsy, Female, Humans, Lipofuscin, Male, Mitochondria, Oxygen Consumption, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Cell Respiration
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