{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:25:12Z","timestamp":1790036712406,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging\u2010associated sarcopenia is driven in part by the progressive loss of type II glycolytic fibers and the functional decline of their resident stem cells, the satellite cells (SCs). We show here that these defects result from attenuation of the hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) signaling pathway and can be reversed by pharmacological HIF\u20101\u03b1 reactivation. In the tibialis anterior muscle of 18\u2010month\u2010old C57BL\/6J mice, HIF\u20101\u03b1 protein abundance decreased by \u224846% and canonical targets (\n                    <jats:italic>Vegf<\/jats:italic>\n                    a,\n                    <jats:italic>Egln1<\/jats:italic>\n                    ) were downregulated in freshly isolated SCs. Treatment of aged SCs with the prolyl hydroxylase inhibitor roxadustat (FG\u20104592) for 48\u2009h restored HIF signaling, upregulated glycolytic enzymes (HK2, GAPDH, ALDO) and the lactate transporter MCT4, and increased intracellular lactate by 1.9\u2010fold. Increased lactate enhanced global histone lactylation, an epigenetic mark that decreased with age. The effect was attenuated by the LDHA inhibitor oxamate, establishing a link between HIF\u2010driven metabolism and chromatin remodeling. HIF\u20101\u03b1 activation slowed old SC proliferation (S phase \u221260%), but decreased the senescence marker p16Ink4a (\u221254%) and increased the stem cell factor\n                    <jats:italic>Pax7<\/jats:italic>\n                    (+1.8\u2010fold), indicating a shift from senescence to a quiescent, regenerative state. When differentiation was induced without drugs, pretreated aged SCs formed hypertrophic myotubes (differentiation index +1.7), exhibited higher ATP content (+1.54\u2010fold), and activated the IGF\u20101\/PI3K\u2013Akt\u2013mTOR pathway, leading to an increase in tropomyosin (\n                    <jats:italic>Tpm1<\/jats:italic>\n                    ) in fast fibers. These results suggest a HIF\u20101\u03b1\u2010lactate\u2010lactylation axis that rejuvenates aged satellite cells and enhances myogenic performance, providing a mechanistic rationale for repurposing roxadustat to alleviate sarcopenia.\n                  <\/jats:p>","DOI":"10.1111\/acel.70411","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:01:20Z","timestamp":1771045280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The HIF\u20101\u03b1 Pathway Regulates Satellite Cell Fate During Aging Through Histone Lactylation"],"prefix":"10.1111","volume":"25","author":[{"given":"Marco","family":"Piccoli","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells for Tissue Engineering IRCCS Policlinico San Donato  Milan Italy"},{"name":"University Vita\u2010Salute San Raffaele  Milan Italy"},{"name":"Institute for Molecular and Translational Cardiology (IMTC) IRCCS Policlinico San Donato  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Mornatti","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells for Tissue Engineering IRCCS Policlinico San Donato  Milan Italy"},{"name":"Institute for Molecular and Translational Cardiology (IMTC) IRCCS Policlinico San Donato  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Lavota","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells for Tissue Engineering IRCCS Policlinico San Donato  Milan Italy"},{"name":"Institute for Molecular and Translational Cardiology (IMTC) IRCCS Policlinico San Donato  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Risuglia","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells for Tissue Engineering IRCCS Policlinico San Donato  Milan Italy"},{"name":"Institute for Molecular and 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