MUSCLE REGENERATION AND AGING

肌肉再生和衰老

• 批准号: 6201004
• 负责人: BRUCE M CARLSON
• 金额: $ 15.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201004
• 关键词: Schwann cells; age difference; aging; cell proliferation; cell type; confocal scanning microscopy; denervation; electron microscopy; electrophysiology; histology; immunocytochemistry; innervation; laboratory rat; morphology; muscle function; muscle satellite cell; muscle transplantation; nervous system regeneration; regeneration; single cell analysis; striated muscles

The overall aims of this Program Project are to test the hypothesis that denervation changes are responsible for much of the deficit in muscle mass and function that is seen in old age and to discover enough about the biology of denervated muscle to be able to devise methods for successfully preventing or reversing the course of denervation atrophy. Project 1 will employ principally morphological methods to investigate both satellite cell biology and to localize in tissue sections important molecules in muscles at various stages of aging and denervation, as well as to asses the success of restoration of denervated and/or aging muscle by grafting or electrical stimulation. In Group Aims 1 and 2, P-1 will provide quantitative data on the numbers and distribution of satellite cells on denervated muscle fibers of young and old rats, as well as localizing by immunocytochemical means molecules of the myogenic regulatory factor family and the proteins EF-1alpha and S1. In addition, P-1 will assess morphologically the success of grafts of denervated and aged muscles into young host rats. In Group Aim 3, p-1 will use satellite cell analysis and molecular localization techniques to test the hypothesis that electrical stimulation of denervated muscle significantly reduces the rate and degree of denervation atrophy. P-1 will also assess the morphology of grafts of stimulated-denervated muscles in testing the hypothesis that grafts of stimulated-denervated muscles recover better than grafts of non-stimulated denervated muscles. For Group aim 4, P-1 will assess the morphology of grafts of muscles that have been reinnervated with either fast or slow nerves in young, adult, old and extremely old rats. These studies are expected to clarify the cellular basis underlying denervation atrophy and the patterns of recovery seen after different periods of denervation of muscle. These data will than be used in the analysis of structural and functional deficits in aging muscle.

该计划项目的总体目的是检验以下假设。 改造的变化是肌肉中大部分赤字的原因 质量和功能在老年时看到，发现足够多的质量和功能 被剥夺肌肉的生物学能够设计方法 成功防止或逆转神经萎缩的过程。 项目1将主要采用形态学方法来调查 卫星细胞生物学和在组织切片中的位置很重要 肌肉中的分子在衰老和神经的各个阶段 并评估恢复已成和/或衰老的成功 肌肉通过嫁接或电刺激。 在小组目标1和2中 P-1将提供有关数量和分布的定量数据 卫星细胞上的老鼠和老鼠的肌肉纤维上的卫星细胞，如 以及通过免疫细胞化学平均分子定位的分子 肌源性调节因子家族和蛋白质EF-1Alpha和S1。 此外，P-1将在形态学上评估移植的成功 将肌肉剥夺并衰老，成为年轻的宿主大鼠。 在AIM 3中， P-1将使用卫星细胞分析和分子定位技术 为了测试未经刺激的肌肉电刺激的假设 显着降低了神经萎缩的速率和程度。 P-1 还将评估受刺激的刺激的移植物的形态 在测试刺激性的嫁接的假设中的肌肉 肌肉比未刺激的无刺激的移植物更好 肌肉。 对于AIM 4，P-1将评估移植物的形态 肌肉已被快速或缓慢的神经加剧的肌肉 年轻，成人，老老鼠。 这些研究是预期的 澄清细胞基础基础神经萎缩和 不同时期的去神经后期看到的恢复模式 肌肉。 这些数据将比在结构和分析中使用 衰老肌肉的功能缺陷。