Aging-related hyperphosphatemia triggers the release of TNF-α from macrophages, promoting indicators of sarcopenia through the reduction of IL-15 expression in skeletal muscle
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Le résumé fourni par la source
AIMS: The association between aging-related hyperphosphatemia and sarcopenia has been documented, and evidence suggests that inflammaging is involved in the manifestation of sarcopenia. The present study investigates whether hyperphosphatemia triggers inflammation, thereby inducing the appearance of sarcopenia along with the cytokines involved in these processes. MATERIALS AND METHODS: RAW 264.7 macrophages were incubated with β-glycerophosphate (BGP), as a phosphate donor, at different time intervals, to assess the production of proinflammatory markers. Conditioned medium from macrophages was collected and added to cultured C2C12 myoblasts to analyse whether proinflammatory molecules, released by macrophages, modified myogenic differentiation, cell senescence or myokine IL-15 expression. A neutralising antibody anti-TNF-α and recombinant IL-15 were added to evaluate the role of these cytokines in the observed effects. Additionally, TNF-α, IL-15, serum phosphate, and sarcopenia signs were evaluated in 5-month-old mice, 24-month-old mice and 24-month-old mice fed with a hypophosphatemic diet. KEY FINDINGS: BGP increased TNF-α expression in macrophages through NFkB activation. Conditioned medium from BGP-treated macrophages impaired myogenic differentiation in differentiating myoblasts and promoted cellular senescence and reduced IL-15 expression in undifferentiated myoblasts. These effects were mediated by TNF-α. Old mice displayed reduced expression of muscle IL-15 and elevated circulating TNF-α, along with increased serum phosphate levels, which correlated with the appearance of sarcopenia indicators. The hypophosphatemic diet prevented these changes in old mice. SIGNIFICANCE: Hyperphosphatemia induces TNF-α production in macrophages, which contributes to the reduced expression of muscular IL-15. This mechanism may play a role in inducing sarcopenia in elderly mice.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Aging-related hyperphosphatemia triggers the release of TNF-α from macrophages, promoting indicators of sarcopenia through the reduction of IL-15 expression in skeletal muscle
- Date Crossref
- 01/05/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Universidad de Alcalá pays non établi dans la noticeUniversité ou école supérieure
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Hospital Universitario Fundación Jiménez Díaz pays non établi dans la noticeÉtablissement de santé
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Fundación Renal Española pays non établi dans la noticeInstitution
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Biomedical Research Foundation pays non établi dans la noticeInstitution
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University of Alcalá pays non établi dans la noticeUniversité ou école supérieure
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Autonomous University of Madrid Institute of Medical Research of the Jiménez Díaz Foundation pays non établi dans la noticeUniversité ou école supérieure
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Foundation for Biomedical Research of the Príncipe de Asturias University Hospital Reina Sofía Institute of Nephrology Research (IRSIN) pays non établi dans la noticeUniversité ou école supérieure
Universidad de Alcalá, Hospital Universitario Fundación Jiménez Díaz et Fundación Renal Española, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.