Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle. 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：老年人处于静息状态时，会诱发营养合成代谢抵抗（nutrient anabolic resistance），进而引发骨骼肌转录与翻译层面的一系列异常级联反应，最终导致肌肉功能障碍。
研究目的：明确静息状态如何改变老年人骨骼肌内亮氨酸（leucine）刺激的分子与通路翻译过程。
实验设计：本研究纳入8名年龄约72岁的老年人（6名女性/2名男性），对其骨骼肌活检样本同时开展核糖体谱分析（ribosomal profiling）与RNA测序（RNA sequencing）。所有受试者接受亮氨酸负荷干预，分别在2周体力活动减少前（健康状态组）及2周后（静息状态组）开展干预；两次访视中，均于亮氨酸摄入后的基线时刻、60分钟（早期响应阶段）及180分钟（晚期响应阶段）采集骨骼肌活检样本。