{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:35:56Z","timestamp":1786988156752,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF 2021R1F1A1048536"],"award-info":[{"award-number":["NRF 2021R1F1A1048536"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The onset of sarcopenia is associated with a decline in vitamin D receptor (VDR) expression, wherein reduced VDR levels contribute to muscle atrophy, while heightened expression promotes muscle hypertrophy. Like VDR, the age-related decline in protein deacetylase sirtuin (SIRT) expression is linked to the development of sarcopenia and age-related muscle dysfunction. This study aimed to investigate whether the VDR agonist 1,25-dihydroxyvitamin D3 (1,25VD3) exerts beneficial effects on muscles through interactions with sirtuins and, if so, the underlying molecular mechanisms. Treatment of 1,25VD3 in differentiating C2C12 myotubes substantially elevated VDR, SIRT1, and SIRT3 expression, enhancing their differentiation. Furthermore, 1,25VD3 significantly enhanced the expression of key myogenic markers, including myosin heavy chain (MyHC) proteins, MyoD, and MyoG, and increased the phosphorylation of AMPK and AKT. Conversely, VDR knockdown resulted in myotube atrophy and reduced SIRT1 and SIRT3 levels. In a muscle-wasting model triggered by IFN-\u03b3\/TNF-\u03b1 in C2C12 myotubes, diminished VDR, SIRT1, and SIRT3 levels led to skeletal muscle atrophy and apoptosis. 1,25VD3 downregulated the increased expression of muscle atrophy-associated proteins, including FoxO3a, MAFbx, and MuRF1 in an IFN-\u03b3\/TNF-\u03b1 induced atrophy model. Importantly, IFN-\u03b3\/TNF-\u03b1 significantly reduced the mtDNA copy number in the C2C12 myotube, whereas the presence of 1,25VD3 effectively prevented this decrease. These results support that 1,25VD3 could serve as a potential preventive or therapeutic agent against age-related muscle atrophy by enhancing the VDR\/SIRT1\/SIRT3 axis.<\/jats:p>","DOI":"10.3390\/nu15224714","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:25:31Z","timestamp":1699356331000},"page":"4714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vitamin D3 Exerts Beneficial Effects on C2C12 Myotubes through Activation of the Vitamin D Receptor (VDR)\/Sirtuins (SIRT)1\/3 Axis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6674-3990","authenticated-orcid":false,"given":"Nurul Fatihah","family":"Talib","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunshu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Clinical Pharmacology and Therapeutics, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea"},{"name":"East-West Bone & Joint Disease Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/ageing\/afz046","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s13539-010-0014-2","article-title":"An overview of sarcopenia: Facts and numbers on prevalence and clinical impact","volume":"1","author":"Morley","year":"2010","journal-title":"J. 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