{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:03:33Z","timestamp":1776974613938,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN-PNRR","award":["P2022Z4EB5"],"award-info":[{"award-number":["P2022Z4EB5"]}]},{"name":"PRIN-PNRR","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Fondazione Perugia","award":["P2022Z4EB5"],"award-info":[{"award-number":["P2022Z4EB5"]}]},{"name":"Fondazione Perugia","award":["21060"],"award-info":[{"award-number":["21060"]}]},{"name":"Fondazione Veronesi","award":["P2022Z4EB5"],"award-info":[{"award-number":["P2022Z4EB5"]}]},{"name":"Fondazione Veronesi","award":["21060"],"award-info":[{"award-number":["21060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Dietary advanced glycation end-products (dAGEs) contained in high-sugar\/fat and ultra-processed foods of the \u201cWestern diet\u201d (WD) pattern predispose to several diseases by altering protein function or increasing oxidative stress and inflammation via RAGE (receptor for advanced glycation end-products). Although elevated endogenous AGEs are associated with loss of muscle mass and functionality (i.e., muscle wasting; MW), the impact of dAGEs on MW has not been elucidated. Here, we show that the most common dAGEs or their precursor, methylglyoxal (MGO), induce C2C12 myotube atrophy as endogenous AGE-derived BSA. ROS production, mitochondrial dysfunction, mitophagy, ubiquitin\u2013proteasome activation, and inhibition of myogenic potential are common atrophying mechanisms used by MGO and AGE-BSA. Although of different origins, ROS are mainly responsible for AGE-induced myotube atrophy. However, while AGE-BSA activates the RAGE-myogenin axis, reduces anabolic mTOR, and causes mitochondrial damage, MGO induces glycolytic stress and STAT3 activation without affecting RAGE expression. Among thirty selected natural compounds, Vaccinium macrocarpon (VM), Camellia sinensis, and chlorophyll showed a surprising ability in counteracting in vitro AGE formation. However, only the standardized VM, containing anti-glycative metabolites as revealed by UHPLC-HRMS analysis, abrogates AGE-induced myotube atrophy. Collectively, our data suggest that WD-linked dAGE consumption predisposes to MW, which might be restricted by VM food supplements.<\/jats:p>","DOI":"10.3390\/antiox14080900","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diet-Derived Advanced Glycation End-Products (AGEs) Induce Muscle Wasting In Vitro, and a Standardized Vaccinium macrocarpon Extract Restrains AGE Formation and AGE-Dependent C2C12 Myotube Atrophy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-493X","authenticated-orcid":false,"given":"Martina","family":"Paiella","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-0647","authenticated-orcid":false,"given":"Tommaso","family":"Raiteri","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Reano","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominga","family":"Manfredelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Manenti","sequence":"additional","affiliation":[{"name":"Laboratori Biokyma Srl, 52031 Anghiari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6919-3862","authenticated-orcid":false,"given":"Giulia","family":"Gentili","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7720-1718","authenticated-orcid":false,"given":"Hajar","family":"Meskine","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Chiappalupi","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5650","authenticated-orcid":false,"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9660-5335","authenticated-orcid":false,"given":"Flavia","family":"Prodam","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-680X","authenticated-orcid":false,"given":"Cinzia","family":"Antognelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-0230","authenticated-orcid":false,"given":"Roccaldo","family":"Sardella","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Migni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-9679","authenticated-orcid":false,"given":"Guglielmo","family":"Sorci","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"},{"name":"Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Salvadori","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-611X","authenticated-orcid":false,"given":"Nicoletta","family":"Filigheddu","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-3379","authenticated-orcid":false,"given":"Francesca","family":"Riuzzi","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Myology (IIM), 06132 Perugia, 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