Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice

• DOI: 10.1152/physiolgenomics.00115.2024
• Publication Date: 2025-03-10T15:01:12Z
• Authors: Shelby C. Osburn; Meghan E. Smith; Devin Wahl; Thomas J. LaRocca
• Keywords: Reverse-transcriptase inhibitor

Aging is the primary risk factor for development of many chronic diseases, including dementia, cardiovascular disease, and diabetes. There significant interest in identifying novel “geroprotective” agents, by repurposing existing drugs, but such treatments may affect organ systems differently. One current example nucleoside reverse transcriptase inhibitor 3TC, which has been increasingly studied as a potential gerotherapeutic. Recent data suggest 3TC reduce inflammation improve cognitive function older mice; however, effects on other tissues aged animals are less well characterized. Here, we use transcriptomics (RNA-seq) targeted metabolomics to investigate influence supplementation skeletal muscle mice. We show that 3TC: (a) does not overtly mass or functional/health markers; (b) largely reverses age-related changes gene expression metabolite signatures; (c) potentially beneficial mitochondrial old via increases antioxidant enzymes decreases reactive oxygen species. Collectively, our results that, addition its protective tissues, have adverse muscle, even protect muscle/mitochondrial health this context.