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It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating \u03b2\u2010hydroxybutyrate (\u03b2\u2010HB) levels. Whether the elevated \u03b2\u2010HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both <jats:italic>Caenorhabditis elegans<\/jats:italic> and mouse models that an increase of \u03b2\u2010HB reverse myofiber atrophy and improves motor functions at advanced ages. \u03b2\u2010HB\u2010induced histone lysine \u03b2\u2010hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that \u03b2\u2010HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia.<\/jats:p>","DOI":"10.1111\/acel.14284","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T08:42:25Z","timestamp":1722328945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Histone \u03b2\u2010hydroxybutyrylation is critical in reversal of sarcopenia"],"prefix":"10.1111","volume":"23","author":[{"given":"Qiquan","family":"Wang","sequence":"first","affiliation":[{"name":"Metabolic Control and Aging Human Aging Research Institute and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Aging and Diseases  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqiang","family":"Lan","sequence":"additional","affiliation":[{"name":"Metabolic Control and Aging Human Aging Research Institute and School of Life 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