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This study investigated the effects of AU on aging-related skeletal muscle atrophy in vitro and in vivo. The results of network pharmacology revealed the potential therapeutic effects of AU on muscle atrophy. In vitro, AU effectively attenuated D-gal-induced cellular damage, reduced the number of senescence-associated \u03b2-galactosidase (SA-\u03b2-Gal)-positive cells, down-regulated the expression levels of muscle atrophy-related proteins Atrogin-1 and MuRF1, and improved myotube differentiation, thereby mitigating myotube atrophy. Notably, AU was found to attenuate oxidative stress and apoptosis in skeletal muscle cells by reducing ROS production, regulating Cleaved caspase3 and BAX\/Bcl-2 expression in apoptotic pathways, and enhancing Sirt1 and PGC-1\u03b1 signaling pathways. In vivo studies demonstrated that AU treatment extended the average lifespan of Caenorhabditis elegans (C. elegans), increased locomotor activity, improved body wall muscle mitochondrial content, and alleviated oxidative damage in C. elegans. These findings suggested that AU can ameliorate aging-related muscle atrophy and show significant potential in preventing and treating muscle atrophy.<\/jats:p>","DOI":"10.3390\/ijms26062626","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T07:02:16Z","timestamp":1741935736000},"page":"2626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Network Pharmacology Combined with Experimental Validation to Investigate the Effects and Mechanisms of Aucubin on Aging-Related Muscle Atrophy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-4163","authenticated-orcid":false,"given":"Wenan","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Modern 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biology, Guangdong Medical University, Zhanjiang 524023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-2880","authenticated-orcid":false,"given":"Yun-Tao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Modern Biochemistry Experimental Center, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Guangdong Ocean University, Zhanjiang 524088, 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