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Alcal\u00e1","doi-asserted-by":"publisher","award":["PIUAH24\/CCS-036"],"award-info":[{"award-number":["PIUAH24\/CCS-036"]}],"id":[{"id":"10.13039\/501100006302","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PIUAH24\/CCS-036"],"award-info":[{"award-number":["PIUAH24\/CCS-036"]}],"id":[{"id":"https:\/\/ror.org\/04pmn0e78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related hyperphosphatemia is increasingly recognized as a contributing factor in sarcopenia. This work studies the metabolic effects of elevated phosphate on muscle. C2C12 cells were differentiated in the absence or presence of 10 mM \u03b2-glycerophosphate (BGP), an exogenous phosphate donor. In addition, quadriceps muscles from four experimental groups of male C57BL\/6J mice were analyzed: young (5 months) and old (24 months) fed with standard diet; old mice fed with hypophosphatemic diet or supplemented with the phosphate binder Velphoro\u00ae, for the last three months of life. Mice were stratified according to sarcopenia degree based on muscle mass, strength and physical performance. Protein levels were determined by immunoblotting and mRNA expression by RT-qPCR. ATP levels were measured by luminescence and L-lactate production, citrate synthase and cytochrome c oxidase activities by colorimetric assays. Mitochondrial content, membrane potential and reactive oxygen species (ROS) were determined by fluorescence assay. BGP-treated cells showed increased glucose transporter 1 (GLUT1) and decreased NADH Dehydrogenase (CI-NDUFB8) protein expression, elevated hexokinase II (HK2), phosphoglycerate kinase 1 (PGK1) and lactate dehydrogenase A (LDHA) mRNA levels, reduced ATP levels, increased lactate production, and decreased mitochondrial enzyme activities. Moreover, BGP increased ROS, diminished mitochondrial membrane potential, and altered fusion\u2013fission dynamics and mitophagy. In aged quadriceps, oxidative phosphorylation (OXPHOS) subunits and superoxide dismutase 2 (SOD2) expression were reduced. The hypophosphatemic diet improved all parameters, whereas Velphoro\u00ae selectively increased Mitochondrial cytochrome C oxidase subunit 1 (CIV-MTCO1) expression. Several altered mitochondrial markers are associated with sarcopenia degree. Altogether, hyperphosphatemia induces metabolic changes that scale with the sarcopenic degree. Our findings show a relevant association between hyperphosphatemia and mitochondrial dysfunction, and they support the potential benefit of phosphate reduction as a strategy to prevent or mitigate sarcopenia.<\/jats:p>","DOI":"10.3390\/ijms27135662","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-Related Hyperphosphatemia Is Associated with Metabolic and Mitochondrial Alterations During Myogenic Differentiation and in Skeletal Muscle from Old Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1071-4449","authenticated-orcid":false,"given":"Mar\u00eda","family":"Martos-Elvira","sequence":"first","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Medicina y Ciencias de la Salud, Departamento de Biolog\u00eda de Sistemas, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Guerrero-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Medicina y Ciencias de la Salud, Departamento de Biolog\u00eda de Sistemas, Alcal\u00e1 de Henares, 28871 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8919-3964","authenticated-orcid":false,"given":"Ariadna","family":"Moreno-Piedra","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5481-3376","authenticated-orcid":false,"given":"Javier","family":"Sanz-Zamora","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Medicina y Ciencias de 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-1680","authenticated-orcid":false,"given":"Susana","family":"L\u00f3pez-Ongil","sequence":"additional","affiliation":[{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040-Renal, 28029 Madrid, Spain"},{"name":"Unidad de Investigaci\u00f3n de la Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica, Hospital Universitario Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares, 28805 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN), Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Olmos","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Medicina y Ciencias de la Salud, Departamento de Biolog\u00eda de Sistemas, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"\u00c1rea 5-Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS, 28034 Madrid, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040-Renal, 28029 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN), Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Piedad","family":"Ruiz-Torres","sequence":"additional","affiliation":[{"name":"Universidad de Alcal\u00e1, Facultad de Medicina y Ciencias de la Salud, Departamento de Biolog\u00eda de Sistemas, Alcal\u00e1 de Henares, 28871 Madrid, Spain"},{"name":"\u00c1rea 5-Fisiolog\u00eda y Fisiopatolog\u00eda Renal y Vascular del IRYCIS, 28034 Madrid, Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientadas a Resultados en Salud (RICORS), RICORS2040-Renal, 28029 Madrid, Spain"},{"name":"Instituto Reina Sof\u00eda de Investigaci\u00f3n Nefrol\u00f3gica (IRSIN), Fundaci\u00f3n Renal I\u00f1igo \u00c1lvarez de Toledo (FRIAT), 28003 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.3803\/EnM.2020.405","article-title":"Sarcopenia and Muscle Aging: A Brief Overview","volume":"35","author":"Dao","year":"2020","journal-title":"Endocrinol. 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