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We examined the effect of AsA deficiency on skeletal muscle using senescence marker protein-30 (SMP30)-knockout (KO) mice that are defective in AsA biosynthesis, which makes this mouse model similar to humans, to clarify the function of AsA in skeletal muscle. Eight-week-old female SMP30-KO mice were divided into the following two groups: an AsA-sufficient group [AsA(+)] that was administered 1.5\u2009g\/L AsA and an AsA-deficient group [AsA(\u2212)] that was administered tap (AsA-free) water. At 4 weeks, the AsA content in the gastrocnemius muscle of AsA(\u2212) mice was 0.7% compared to that in the gastrocnemius muscle of AsA(+) mice. Significantly lower weights of all muscles were observed in AsA(\u2212) mice than those in AsA(+) mice at 12 and 16 weeks. The cross-sectional area of the soleus was significantly smaller in AsA(\u2212) mice at 16 weeks than that in AsA(+) mice. The physical performance of AsA(\u2212) mice was significantly less than that of AsA(+) mice at 12 weeks. Following AsA deficiency for 12 weeks, the expression of ubiquitin ligases, such as atrogin1\/muscle atrophy F-box (MAFbx) and muscle RING-finger protein 1 (MuRF1), was upregulated. Furthermore, all detected effects of AsA deficiency on muscles of the AsA(\u2212) group at 12 weeks were restored following AsA supplementation for 12 weeks. Thus, longer-term AsA deficiency is associated with muscle wasting, that this can be reversed by restoring AsA levels.<\/jats:p>","DOI":"10.1038\/s41598-019-41229-7","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T07:03:45Z","timestamp":1553065425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Vitamin C deficiency causes muscle atrophy and a deterioration in physical performance"],"prefix":"10.1038","volume":"9","author":[{"given":"Shoko","family":"Takisawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Funakoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7205-8573","authenticated-orcid":false,"given":"Tomofumi","family":"Yatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisaburo","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Aigaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Machida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7875-7482","authenticated-orcid":false,"given":"Akihito","family":"Ishigami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"41229_CR1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nchembio.85","volume":"4","author":"CC Winterbourn","year":"2008","unstructured":"Winterbourn, C. 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