{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:46:52Z","timestamp":1792482412396,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcopenia, an age\u2010related clinical syndrome characterized by reduced skeletal muscle mass and strength, often leads to a loss of physical function. Nucleotides (NTs) supplementation is a potential strategy for preventing age\u2010related sarcopenia as evidence suggests that NTs declined in muscles with aging, and 5\u2032\u2010CMP, 5\u2032\u2010UMP can mitigate muscle atrophy in C2C12 myotubes. This study aimed to investigate the effects of NTs supplementation on sarcopenia and its possible mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Senescence\u2010accelerated mouse prone\u20108 (SAMP8) mice and C2C12 cells were used to assess the effect of NTs on sarcopenia. We fed an NTs\u2010enriched mixture to SAMP8 mice starting from the age of 3\u2009months for 9\u2009months or 15\u2009months. NTs' effects on H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced C2C12 atrophy cells were tested using nucleotide monomers and mixtures. The body composition was measured by EchoMRI analysis meter. Physical performance was tested including grip strength, wire hang, horizontal bar and gait test. The immunofluorescence staining was used to evaluate the cross\u2010sectional area (CSA) or type of muscle fibers and the diameter of myotubes. RT\u2010qPCR, western blot, RNA sequencing (RNA\u2010seq) and targeted metabolomic analyses were conducted to elucidate the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results demonstrated that NTs significantly increased lean mass\/body weight (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, <jats:italic>\u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.434), the grip strength at 7 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, <jats:italic>\u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.312), 9 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, <jats:italic>\u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.293) and 11 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, <jats:italic>\u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.507) months of age and the gait speed of mice (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001<jats:italic>, \u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.3861). The immunofluorescence staining results indicated that NTs increased the CSA of muscle fibers (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, <jats:italic>\u03b7<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.1081), especially for type IIb fibres. The RNA\u2010seq results showed that NTs significantly downregulated the expression of sarcopenia\u2010related genes (Trim63, Dkk3 and Mt1). The downregulation of Fbxo32, Trim63, Dkk3, Mt1 and p53 genes in NTs intervention group was confirmed by RT\u2010qPCR and\/or western blot (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Integrated analyses of RNA\u2010seq and metabolomic showed that NTs could cause changes in metabolites, such as ketoleucine, 3\u2010hydroxylisovalerylcarnitine and 3\u2010methyl\u20102\u2010oxovaleric acid, which could further regulate sarcopenia\u2010related genes and inhibit protein degradation and promote protein synthesis. In\u00a0vitro studies confirmed that NTs increased myotubes diameter and decreased expression of sarcopenia\u2010related genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings reveal the protective role of NTs in improving muscle protein balance during ageing, suggesting they may serve as a conditionally essential nutrient for older individuals. Further research is needed to explore the efficacy and safety of NTs supplementation for sarcopenia in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.70002","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T03:50:20Z","timestamp":1754020220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exogenous Nucleotides Supplementation Attenuates Age\u2010Related Sarcopenia"],"prefix":"10.1002","volume":"16","author":[{"given":"Xin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"},{"name":"Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Science Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Public Health Inner Mongolia Medical University  Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"An","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-5840","authenticated-orcid":false,"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy169"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539\u2010014\u20100132\u20103"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2017.08.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.064071"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20108706\u20101_17"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(04)00400\u20103"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12709"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12166"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1079\/bjn2001467"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21040435"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009\u20102609"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010014\u20109492\u20105"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00134"},{"key":"e_1_2_7_16_1","first-page":"409","article-title":"Acceleration of Muscle Regeneration by Nucleotide Administration. 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