Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle

• DOI: 10.1093/gerona/glab077
• Publication Date: 2021-03-11T19:29:40Z
• Authors: Ziad S Mahmassani; Alec I McKenzie; Jonathan J Petroc...; Naomi M de Hart; Dennis K Fix; Joshua J Kelly; Lisa M Baird; Michael T Howard; Micah J Drummond
• Keywords: Translational regulation; Ribosome profiling; Translational efficiency

Abstract Periods of inactivity experienced by older adults induce nutrient anabolic resistance creating a cascade skeletal muscle transcriptional and translational aberrations contributing to dysfunction. The purpose this study was identify how alters leucine-stimulated translation molecules pathways within the adults. We performed ribosomal profiling alongside RNA sequencing from biopsies taken (n = 8; ~72 years; 6 F/2 M) in response leucine bolus before (Active) after (Reduced Activity) 2 weeks reduced physical activity. At both visits, were at baseline, 60 minutes (early response), 180 (late response) ingestion. Previously identified inactivity-related gene transcription changes (PFKFB3, GADD45A, NMRK2) heightened with corresponding translation. In contrast, also stimulated efficiency several transcripts manner not explained mRNA abundance (“uncoupled translation”). Inactivity eliminated uncoupled for transcripts, most mRNAs encoding proteins. Ingenuity Pathway Analysis discordant circadian as result such PER2 PER3 despite unchanged transcription. demonstrate “uncoupled translation” proteins regulators otherwise detectable traditional sequencing. Innovative techniques continues further our understanding activity mediates regulation, will set path toward therapies that can restore optimal protein synthesis on transcript-specific level combat negative consequences aging muscle.