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Glucocorticoid intermittence coordinates rescue of energy and mass in aging-related sarcopenia through the myocyte-autonomous PGC1alpha-Lipin1 transactivation

Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once...

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Detalles Bibliográficos
Autores principales: Prabakaran, Ashok Daniel, McFarland, Kevin, Miz, Karen, Durumutla, Hima Bindu, Piczer, Kevin, El Abdellaoui Soussi, Fadoua, Latimer, Hannah, Werbrich, Cole, Blair, N. Scott, Millay, Douglas P, Prideaux, Brendan, Finck, Brian N, Quattrocelli, Mattia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614926/
https://www.ncbi.nlm.nih.gov/pubmed/37905062
http://dx.doi.org/10.1101/2023.10.16.562573
Descripción
Sumario:Sarcopenia burdens the elderly population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are missing. The glucocorticoid prednisone remodels muscle metabolism based on frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone rescued muscle quality in aged 24-month-old mice to levels comparable to young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing PGC1alpha and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1alpha, which was required for the treatment-driven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1alpha upregulation to the stimulation of both oxidative and anabolic capacities. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.