{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:10:03Z","timestamp":1780103403533,"version":"3.54.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501893"],"award-info":[{"award-number":["82501893"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203191"],"award-info":[{"award-number":["82203191"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024QH510"],"award-info":[{"award-number":["ZR2024QH510"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Sarcopenia contributes to all\u2010cause mortality in the elderly; however, there is no specific treatment. Mesenchymal stromal cells (MSCs) ameliorate age\u2010related muscle loss and dysfunction and are potential therapeutic candidates for sarcopenia. However, their activity is easily affected by the surrounding environment and they are prone to replicative senescence during in\u00a0vitro culture. Therefore, a drug that delays aging and enhances its function is required. Here, we investigated whether nicotinamide adenine dinucleotide (NAD\n +<\/jats:sup>\n ) pretreatment enhances the therapeutic efficacy of MSCs on skeletal muscle atrophy and its underlying mechanism in a D\u2010galactose (D\u2010gal)\u2013induced mouse model.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The administration of D\u2010gal to mice induces a range of age\u2010associated characteristics and is commonly used in research on age\u2010related muscle atrophy. Therefore, in this study, C57BL\/6\u2009J mice and C2C12\u2010differentiated myotubes exposed to D\u2010gal were used to explore the effects of MSCs\/NAD\n +<\/jats:sup>\n \u2010MSCs on muscle atrophy. MSCs\/NAD\n +<\/jats:sup>\n \u2010MSCs were injected into the skeletal muscles of the hind limbs every 7\u2009days for six cycles. Treadmill running and grip strength tests were used to evaluate muscle strength. Muscle weight and fibre cross\u2010sectional area (CSA) were used to measure muscle mass. Multiomics analysis of quadriceps and NAD\n +<\/jats:sup>\n \u2010pretreated MSCs (NAD\n +<\/jats:sup>\n \u2010MSCs), Western blotting of muscle atrophy signalling, including Atrogin 1 and MuRF1, the mitochondrial complex, fatty acid oxidation indicators and Seahorse analysis were performed to explore the underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n MSCs increased grip strength (\n p<\/jats:italic>\n \u2009=\u20090.0005), running endurance (\n p<\/jats:italic>\n \u2009=\u20090.0006) and muscle mass (\n p<\/jats:italic>\n \u2009=\u20090.0165 for tibialis anterior [TA] muscle,\n p<\/jats:italic>\n \u2009=\u20090.0049 for soleus [SO] muscle) in D\u2010gal\u2013treated mice, with elevated muscle fibre CSA (\n p<\/jats:italic>\n \u2009<\u20090.0001) and reduced Atrogin 1 (\n p<\/jats:italic>\n \u2009=\u20090.0242) and MuRF1 expression (\n p<\/jats:italic>\n \u2009=\u20090.0009). NAD\n +<\/jats:sup>\n pretreatment increased the effect of MSCs on muscle atrophy (\n p<\/jats:italic>\n \u2009=\u20090.0009 for grip strength,\n p<\/jats:italic>\n \u2009=\u20090.0169 for running endurance,\n p<\/jats:italic>\n \u2009=\u20090.0506 for TA muscle weight,\n p<\/jats:italic>\n \u2009=\u20090.0238 for SO muscle weight,\n p<\/jats:italic>\n \u2009=\u20090.0014 for muscle fibre CSA,\n p<\/jats:italic>\n \u2009=\u20090.0005 for Atrogin 1 expression and\n p<\/jats:italic>\n \u2009=\u20090.0223 for MuRF1 expression). MSCs\/NAD\n +<\/jats:sup>\n \u2010MSCs activated the SIRT1\/PGC\u20101\u03b1 signalling, enhanced mitochondrial function and fatty acid oxidation in D\u2010gal\u2013induced mice and C2C12 myotubes. SIRT1 knockdown weakened the beneficial effects of MSCs\/NAD\n +<\/jats:sup>\n \u2010MSCs on muscle atrophy. RNA\u2010seq of MSCs\n \/<\/jats:bold>\n NAD\n +<\/jats:sup>\n \u2010MSCs and proteomic analysis of their supernatants revealed that NAD\n +<\/jats:sup>\n enhanced the therapeutic effect of MSCs by promoting NAMPT secretion.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n NAD\n +<\/jats:sup>\n enhances the therapeutic effect of MSCs on D\u2010gal\u2013induced muscle atrophy by promoting NAMPT secretion, which acts on the SIRT1 signaling pathway, and improves mitochondrial function and fatty acid oxidation in skeletal muscles. This study provides new insights and a theoretical basis for clinical treatment of sarcopenia.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70142","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:05:12Z","timestamp":1765526712000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["NAD\n +<\/sup>\n Enhanced Mesenchymal Stromal Cells Effect on Muscle Atrophy by Improving SIRT1\u2010Mediated Mitochondrial Function via NAMPT"],"prefix":"10.1002","volume":"16","author":[{"given":"Jia","family":"Song","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chromic Metabolic Diseases; Institute of Endocrine and Metabolic Diseases of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"The First Clinical Medical College, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"The First Clinical Medical College, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"The First Clinical Medical College, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longqing","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"The First Clinical Medical College, Cheeloo College of Medicine Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinguo","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chromic Metabolic Diseases; Institute of Endocrine and Metabolic Diseases of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chromic Metabolic Diseases; Institute of Endocrine and Metabolic Diseases of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shandong Engineering & Technology Research Center for Tumor Marker Detection The Second Qilu Hospital of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University Jinan Shandong China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chromic Metabolic Diseases; Institute of Endocrine and Metabolic Diseases of Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13037"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13115"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.14053"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.3604"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010024\u201000550\u2010w"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005843\u20108"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010020518\u2010114310"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201593084"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8059"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802457RR"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000797\u20108"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153877"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115265"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116917"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.22\u201000132"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29456"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160235"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13717"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2022.103424"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u201000313\u2010x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010023\u201001073\u20102"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010019\u20101569\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13177"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000752\u2010w"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202315997"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.117"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.09.003"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.015"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395\u2010025\u201000377\u20103"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201013694\u20101"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.10.021"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12568"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438\u2010022\u201001878\u20102"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2012.00844.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"crossref","unstructured":"L.Tian W.Cao R.Yue et\u00a0al. \u201cPretreatment With Tilianin Improves Mitochondrial Energy Metabolism\u2002and Oxidative Stress in Rats With Myocardial Ischemia\/Reperfusion Injury via AMPK\/SIRT1\/PGC\u20101 Alpha Signaling Pathway \u201d139 no.4(2019):352\u2013360 https:\/\/doi.org\/10.1016\/j.jphs.2019.02.008.","DOI":"10.1016\/j.jphs.2019.02.008"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab4138"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.05.013"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.04.005"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70142","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:42:03Z","timestamp":1772959323000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcsm.70142"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70142","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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