MUSCLE DENERVATION AND REGENERATION--INFLUENCE OF AGING

随着个体年龄的增长，失神经肌肉纤维变得越来越多， 骨骼肌肉系统的突出组成部分，无论是通过 随着年龄的增长，运动单位的正常重塑， 通过创伤性事件，导致崩溃， 肌肉纤维的再生。 该项目的总体目标是 理解质量和力量下降的基础，以及 急剧减少的恢复能力，在失神经肌肉在两个 年轻和年老的动物，并确定预防或 逆转去神经支配的影响。 具体假设和 实验提出了四个方面：1）了解生物学 年轻和老年大鼠的失神经肌肉; 2）测试 假设去神经支配是许多退化的基础， 在极端老年时发现的肌肉变化; 3）识别 失神经支配的维持和恢复的机制 肌肉通过电刺激; 4）测试假设， 神经的类型和肌肉的类型都决定了 肌肉再生是随着动物年龄的增长，特别是在极端的老年。 该项目涉及一个专门从事以下工作的实验室联合体： 形态学，生理学，分子生物学和生物化学，以及许多 的实验将在由组提供的肌肉上进行。 通过动物外科核心进行实验。 具体技术 包括电子和共聚焦显微镜、细胞培养 免疫细胞化学，收缩特性的体外分析， 肌肉，体内运动单位分析，原位杂交，北方和 蛋白质印迹、RNA酶保护测定和细胞转染。 肌肉无力是一个主要的限制，对许多健康的生活方式 老年人。 从这方面的研究中得到的信息是， 项目预计将应用于预防和 治疗老年人肌肉无力。

As an individual ages, denervated muscle fibers become an increasingly prominent component of the skeletal musculature, whether through the normal remodelling of motor units that occurs with aging or through traumatic events that result in the breakdown and regeneration of muscle fibers. The overall goal of this project is to understand the basis for the decline in mass and force, as well as the sharply reduced restorative capacity, in denervated muscle in both young and old animals and to identify means for preventing or reversing the effects of denervation. Specific hypotheses and experiments are proposed in four areas: 1) Understanding the biology of denervated muscle in both young and old rats; 2) testing the hypothesis that denervation is a basis for many of the regressive changes found in muscle during extreme old age; 3) identifying mechanisms underlying the maintenance and restoration of denervated muscle through electrical stimulation; 4) testing the hypothesis that both the type of nerve and type of muscle determine the success of muscle regeneration as an animal ages, particularly in extreme old age. The Project involves a consortium of laboratories specializing in morphology, physiology, molecular biology and biochemistry, and many of the experiments will be conducted on muscle supplied from group experiments through an Animal Surgery core. Specific techniques include electron and confocal microscopy, cell culture, immunocytochemistry, in vitro analysis of contractile properties of muscles, in vivo motor unit analysis, in situ hybridization, Northern and Western blotting, RNase protection assays, and transfection of cells. Muscle weakness is a major limitation on a healthy lifestyle for many older individuals. The information learned from research done on this Program Project is expected to be applied to both the prevention and treatment of muscle weakness in the elderly.