| First Author | Prabakaran AD | Year | 2024 |
| Journal | J Clin Invest | Volume | 134 |
| Issue | 11 | PubMed ID | 38702076 |
| Mgi Jnum | J:349447 | Mgi Id | MGI:7646813 |
| Doi | 10.1172/JCI177427 | Citation | Prabakaran AD, et al. (2024) Intermittent glucocorticoid treatment improves muscle metabolism via the PGC1alpha/Lipin1 axis in an aging-related sarcopenia model. J Clin Invest 134(11) |
| abstractText | Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha) and its cofactor 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 myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1alpha upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia. |
