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

Background: Periods of inactivity experienced by older adults induce nutrient anabolic resistance creating a cascade of skeletal muscle transcriptional and translational aberrations contributing to muscle dysfunction. Objective: To identify how inactivity alters leucine-stimulated translation of molecules and pathways within the skeletal muscle of older adults. Overall design: Design: We performed ribosomal profiling alongside RNA sequencing from skeletal muscle biopsies taken from older adults (n=8; ~72y; 6F/2M) in response to a leucine bolus before (Healthy) and after (Inactive) 2-weeks of reduced physical activity. At both visits, muscle biopsies were taken at baseline, 60min (early response), and 180min (late response) after leucine ingestion.

研究背景：老年人长期久坐不动可诱发营养合成代谢抵抗，进而引发骨骼肌转录与翻译层面的一系列异常改变，最终导致肌肉功能障碍。
研究目的：明确运动不足如何改变老年人骨骼肌内亮氨酸刺激下的分子及通路翻译进程。
整体实验设计：本研究针对8名老年受试者（平均年龄约72岁，其中女性6名、男性2名）的骨骼肌活检样本，同步开展核糖体谱分析（ribosomal profiling）与RNA测序（RNA sequencing）。受试者分别在2周体力活动减少前（健康状态）与后（运动不足状态）接受亮氨酸单次冲击给药，并在两次访视中，于亮氨酸摄入后的基线时刻、60分钟（早期应答阶段）及180分钟（晚期应答阶段）采集肌肉活检样本。