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The senescence-accelerated prone 8 (SAMP8) mouse model, known for its rapid aging and early cognitive decline, serves as an essential model for studying age-related muscle degeneration. While previous studies have shown that exercise attenuates muscle atrophy by promoting regeneration and improving strength, the underlying metabolic mechanisms remain poorly understood. This study used the SAMP8 model to evaluate the effects of exercise on muscle atrophy and associated metabolic changes. Our results show that exercise promoted muscle growth by reducing body weight, increasing skeletal muscle mass, and decreasing fat accumulation. Furthermore, exercise improved grip strength, muscle tone, and muscle fiber cross-sectional area, thereby preserving muscle functionality. NMR-based metabolomic analysis identified key metabolic pathways modulated by exercise, including glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; pyruvate metabolism; and taurine and hypotaurine metabolism. These findings underscore the therapeutic potential of exercise in combating age-related muscle wasting and elucidate the metabolic pathways underlying its benefits.<\/jats:p>","DOI":"10.3390\/molecules30092003","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T06:49:02Z","timestamp":1746082142000},"page":"2003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exercise Attenuates Skeletal Muscle Atrophy in Senescent SAMP8 Mice: Metabolic Insights from NMR-Based Metabolomics"],"prefix":"10.3390","volume":"30","author":[{"given":"Wenfang","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province, High-Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1796-4158","authenticated-orcid":false,"given":"Linglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province, High-Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifen","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province, High-Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-0169","authenticated-orcid":false,"given":"Caihua","family":"Huang","sequence":"additional","affiliation":[{"name":"Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Technical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province, High-Field NMR Center, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/ggi.12720","article-title":"Prevalence of sarcopenia in older Brazilians: A systematic review and meta-analysis","volume":"17","author":"Diz","year":"2017","journal-title":"Geriatr. 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