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ResearchIn-Press PreviewAgingMuscle biology Open Access | 10.1172/JCI177427
1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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1The Heart Institute, Division of Molecular Cardiovascular Biology, CCHMC and Department of Pediatrics, UC College of Medicine, Cincinnati, United States of America
2Department of Pharmacology and Toxicology, UAMS College of Medicine and Central Arkansas VA Healthcare System, Little Rock, United States of America
3Department of Neuroscience, Cell Biology, and Anatomy, The University of Texas Medical Branch, Galveston, United States of America
4Department of Medicine, Washington University in St. Louis, St. Louis, United States of America
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Published May 3, 2024 - More info
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 PGC1α and its co-factor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatment-driven increase in carbon shuttling from glucose to amino acid biogenesis. We also probed the myocyte-specific Lipin1 as non-redundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes to coordinately rescue energy and mass in sarcopenia.