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Cited by 63Muscle Physiology and DisordersNutrition and Health in AgingExercise and Physiological Responses

Reactive oxygen species in the pathogenesis of sarcopenia

Open access
Xu, Hongyang, Brown, Jacob L., Bhaskaran, Shylesh, Van Remmen, Holly·2025·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2024.11.046PMC PMC11816180
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Abstract

One of the most critical factors impacting healthspan in the elderly is the loss of muscle mass and function, clinically referred to as sarcopenia. Muscle atrophy and weakness lead to loss of mobility, increased risk of injury, metabolic changes and loss of independence. Thus, defining the underlying mechanisms of sarcopenia is imperative to enable the development of effective interventions to preserve muscle function and quality in the elderly and improve healthspan. Over the past few decades, understanding the roles of mitochondrial dysfunction and oxidative stress has been a major focus of studies seeking to reveal critical molecular pathways impacted during aging. In this review, we will highlight how oxidative stress might contribute to sarcopenia by discussing the impact of oxidative stress on the loss of innervation and alteration in the neuromuscular junction (NMJ), on muscle mitochondrial function and atrophy pathways, and finally on muscle contractile function.

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Crossref · 10.1016/j.freeradbiomed.2024.11.046

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  • Mitochondrial dysfunction leads to decreased energy production in muscle cells, impairing their ability to maintain mass and function.

    “Mitochondrial dysfunction leads to decreased energy production in muscle cells, impairing their ability to maintain mass and function [7,8].”

    From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [7]

    The “Mitochondrial function and ROS generation” section (page unavailable) links mitochondrial dysfunction in skeletal muscle to altered energetics and reports reduced respiratory-complex activity and oxidative phosphorylation in sarcopenia. The “Impact of oxidative stress and lipid hydroperoxides on muscle proteostasis” section links mitochondrial oxidative stress to loss of muscle mass. The copy does not establish the claim’s specific causal chain that decreased energy production impairs maintenance of muscle mass and function; it emphasizes ROS and proteolysis instead. (LLM, conf=0.83)

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Research works printed but not linked: 2

  1. [146]Xu H,, Muscle mitochondrial catalase expression prevents neuromuscular junction disruption, atrophy, and weakness in a mouse model of accelerated sarcopenia, J. Cachexia Sarcopenia Muscle. 12 (6) (2021) 1582– 1596. 34559475 PMC8718066
  2. [147]McClung JM,, Calpain-1 is required for hydrogen peroxide-induced myotube atrophy, Am. J. Physiol. Cell Physiol. 296 (2) (2009) C363– C371. 19109522 PMC2643855

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Authors
Xu, H., Brown, J. L., Bhaskaran, S., & Van Remmen, H.
Affiliations
Oklahoma Medical Research Foundation (US)
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2025-02
Volume
227
Pages
446-458
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2024.11.046
PMC
PMC11816180
OpenAlex
W4404813617
Cited by
61
References
206
Citations by year
2026: 34 · 2025: 27
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • National Institute on Aging
  • US Department of Veterans Affairs
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
sarcopenia, reactive oxygen species, oxidative stress, muscle atrophy, muscle weakness, mitochondrial dysfunction, neuromuscular junction, aging, healthspan, muscle contractility, older adults
MeSH terms
Aging, Animals, Humans, Mitochondria, Mitochondria, Muscle, Muscle Contraction, Muscular Atrophy, Neuromuscular Junction, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Sarcopenia

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