{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:16:52Z","timestamp":1789751812702,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>We previously reported that elevated expression of phospholipid hydroperoxide glutathione peroxidase 4, an enzyme that regulates membrane lipid hydroperoxides, can mitigate sarcopenia in mice. However, it is still unknown whether a pharmacological intervention designed to modulate lipid hydroperoxides might be an effective strategy to reduce sarcopenia in aged mice. Here we asked whether a newly developed compound, CMD\u201035647 (CMD), can reduce muscle atrophy induced by sciatic nerve transection. We treated mice daily with vehicle or CMD (15\u00a0mg\/kg, <jats:sc>i.p.<\/jats:sc> injection) starting 1\u00a0day prior to denervation. CMD treatment reduced hydroperoxide generation and blunted muscle atrophy by over 17% in denervated muscle. To test whether CMD can reduce ageing\u2010induced muscle atrophy and weakness, we treated mice with either vehicle or CMD (15\u00a0mg\/kg, <jats:sc>i.p.<\/jats:sc> injection) 3\u00a0days per week for 8\u00a0months, starting at 18\u00a0months of age until 26\u00a0months of age. We measured muscle mass, functional status of neuromuscular junctions, muscle contractile function and mitochondrial function in control and CMD\u2010treated 26\u2010month\u2010old female mice. Treatment with CMD conferred protection against muscle atrophy in both tibialis anterior and extensor digitorum longus that was associated with maintenance of fibre size of MHC 2b and 2x fibres. Mitochondrial respiration was also protected in CMD\u2010treated mice. We also found that muscle force generation was protected with CMD treatment despite denervation in \u223c25% of the muscle fibres. Overall, this study shows that pharmacological interventions designed to reduce lipid hydroperoxides might be effective for preventing sarcopenia.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16502-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Sarcopenia in aged mice is associated with muscle loss, contractile dysfunction, denervation, and reduced mitochondrial respiration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CMD\u201035647 is a pharmocological compound that can neutralize lipid hydroperoxides.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>8 month treatment of CMD\u201035647 mitigated muscle atrophy in tibialis anterior and extensor digitorum longus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>8 month treatment of CMD\u201035647 improved muscle function in aged mice independent of the neuromuscular junction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Aged mice treated with CMD\u201035647 had greater respiration in red gastrocnemius muscle when compared to vehicle treated mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287090","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T18:19:08Z","timestamp":1736360348000},"page":"837-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacological reduction of lipid hydroperoxides as a potential modulator of sarcopenia"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-7924","authenticated-orcid":false,"given":"Jacob 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