MUSCLE DENERVATION AND REGENERATION--INFLUENCE OF AGING

随着个人年龄的增长，失神经肌肉纤维变得越来越多 骨骼肌肉系统的重要组成部分，无论是通过 随老化或老化而发生的发动机部件的正常改装 通过导致精神崩溃的创伤性事件 肌肉纤维的再生。这个项目的总体目标是 理解质量和力下降的基础，以及 两组失神经肌肉的恢复能力急剧下降 幼年和年老的动物，并确定预防或 逆转去神经的影响。具体的假设和 建议在四个方面进行实验：1)理解生物学 对幼年和老年大鼠失神经肌肉的影响；2)测试 认为去神经是许多退行性疾病的基础的假说 在极端老年期间发现肌肉的变化；3)识别 失神经维持和恢复的机制 通过电刺激肌肉；4)检验假设 神经和肌肉的类型都决定了手术的成功 随着动物年龄的增长，肌肉的再生，特别是在极老的时候。 该项目涉及一个实验室联盟，专门从事 形态、生理学、分子生物学和生物化学，以及许多 部分实验将在团体提供的肌肉上进行 通过动物外科核心进行的实验。具体技术 包括电子显微镜和共聚焦显微镜、细胞培养 免疫细胞化学，体外分析血管收缩特性 肌肉，活体运动单位分析，原位杂交，Northern和 Western blotting、核糖核酸酶保护分析和细胞转染。 对许多人来说，肌肉无力是健康生活方式的主要限制 年纪较大的个体。从对此所做的研究中获得的信息 计划项目预计将同时应用于预防和 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.