Aging increases the oxidation of dichlorohydrofluorescein in single isolated skeletal muscle fibers at rest, but not during contractions
Open accessAbstract
An increase in the activity of reactive oxygen species (ROS) has been implicated in the mechanisms of loss of skeletal muscle that occurs during aging, but few studies have attempted to directly assess activities in intact muscle fibers. The current project used the nonspecific fluorescent probe for ROS and reactive nitrogen species, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein (CM-DCFH), in single, isolated, mature skeletal muscle fibers from adult and old mice in addition to biochemical measurements of key regulatory proteins for ROS in muscles of these animals. Data confirmed the changes in key regulatory processes for ROS (increased glutathione peroxidase 1 and catalase activities and reduced total glutathione content) previously reported in muscle from old mice and showed increased CM-DCFH oxidation in muscle fibers from old mice at rest and indicate that these changes are likely due to an increase in generation of oxidants rather than a lack of scavenging capacity. The increased CM-DCFH oxidation persisted even when cellular defenses against oxidants were increased by loading fibers from young and old mice with glutathione. During contractile activity, and in contrast to the increase observed in fibers from young mice, there was no further increase in CM-DCFH oxidation in muscle fibers from old mice. These data also suggest that the defect in short-term adaptations to contractions that occurs in old mice may be related to a diminished, or absent, increase in the muscle generation of ROS and/or reactive nitrogen species that normally accompanies contractile activity in young mice.
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Isolated muscle fibers from old mice generate more ROS than young adult mice.
“isolated muscle fibers from old mice generate more ROS than young adult mice”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Palomero et al., 2013
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Altab, G., Merry, B. J., Beckett, C. W., Raina, P., Lopes, I., Goljanek‐Whysall, K., & de Magalhães, J. P. (2025) · BMC Genomics · doi:10.1186/s12864-024-11051-1 · Cited by 12 · see citing works
Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice
Cowley, P. M., Nair, D. R., DeRuisseau, L. R., Keslacy, S., Atalay, M., & DeRuisseau, K. C. (2017) · Redox Biology · doi:10.1016/j.redox.2017.07.003 · Cited by 12 · see citing works
Redox Homeostasis in Age-Related Muscle Atrophy
Sakellariou, G. K., & McDonagh, B. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1435-3_13 · Cited by 11 · see citing works
Mechanistic models to guide redox investigations and interventions in musculoskeletal ageing
Jackson, M. J. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.01.020 · Cited by 11 · see citing works
Skeletal muscle transcriptomics identifies common pathways in nerve crush injury and ageing
Staunton, C. A., Owen, E., Hemmings, K., Vasilaki, A., McArdle, A., Barrett‐Jolley, R., & Jackson, M. J. (2022) · Skeletal Muscle · doi:10.1186/s13395-021-00283-4 · Cited by 10 · see citing works
Associations Among Physical Activity Level and Skeletal Muscle Antioxidants in Older Adults
Timmerman, K. L., Ballard, K. D., Deal, M. A., Tagariello, L. C., Karrow, J. M., Volk, G. A., Meisler, A. J., Connors, I. D., & Mott, R. E. (2020) · Journal of Physical Activity and Health · doi:10.1123/jpah.2020-0082 · Cited by 10 · see citing works
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Cuijpers, I., Dohmen, C. G. M., Bouwman, F. G., Troost, F. J., & Sthijns, M. M. J. P. E. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1377071 · Cited by 9 · see citing works
Dietary nitrate supplementation mitigates age‐related changes at the neuromuscular junction in mice
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Jackson, M. J. (2025) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2025.02.002 · Cited by 5 · see citing works
Xirouchaki, C. E., García-Domínguez, E., Coughlan, E., McGrath, M. J., Giri, S., Liang, S., Wiede, F., Bigot, A., Sadoshima, J., Gómez-Cabrera, M., et al. (2026) · Science Advances · doi:10.1126/sciadv.adz1953 · Cited by 4 · see citing works
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Análises das Capacidades Aeróbia e Anaeróbia de Ratos Adultos e Idosos
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A decline in skeletal muscle NOX4 abrogates adaptive homeostasis and exacerbates ageingPreprint
Xirouchaki, C. E., Coughlan, E., García-Domínguez, E., Giri, S., McGrath, M. J., Wiede, F., Sadoshima, J., Roman, W., Gomez-Cabrera, M. C., Philp, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.27.714615
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Unraveling skeletal muscle senescence in an in vitro cell culture model
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Ostrom, E. L., Mattson-Hughes, A., McDonald, J., Bammler, T. K., Day, N. J., Gaffrey, M. J., Trejo, J. B., Qian, W., Hagy, B., Giorgione, J. R., et al. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.10.001
- Authors
- Palomero, J., Vasilaki, A., Pye, D., McArdle, A., & Jackson, M. J.
- Affiliations
- Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom
- University of Liverpool (GB)
- Corresponding author
- Jackson, Malcolm J.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2013-08-15
- Volume
- 305
- Issue
- 4
- Pages
- R351-R358
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC3833391
- OpenAlex
- W2049797752
- Cited by
- 71
- References
- 62
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 1 · 2014: 4 · 2013: 2
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- Gredos (University of Salamanca) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (073263 ⁄ Z ⁄ 03)
- Medical Research Council (MR/K006312/1)
- National Institute on Aging (P01AG020591, AG020591-06)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- skeletal muscle aging, reactive oxygen species, reactive nitrogen species, isolated muscle fibers, glutathione peroxidase 1, catalase, glutathione, muscle contraction, oxidative stress, muscle atrophy
- MeSH terms
- Glutathione Peroxidase GPX1, Adaptation, Physiological, Age Factors, Aging, Animals, Catalase, Female, Fluoresceins, Fluorescent Dyes, Glutathione, Glutathione Peroxidase, Mice, Inbred C57BL, Muscle Contraction, Oxidation-Reduction, Time Factors, Oxidants, Reactive Oxygen Species, Oxidative Stress, Muscle Fibers, Skeletal, Reactive Nitrogen Species, Mice
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