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标是检验以下假设 失神经变化是肌肉缺陷的主要原因。 在老年时看到的质量和功能，并发现足够的 失神经肌肉的生物学能够设计出方法 成功地防止或逆转了去神经萎缩的过程。 项目1将主要使用形态学方法来研究 无论是卫星细胞生物学还是组织切片定位都很重要 在衰老和失神经的不同阶段，肌肉中的分子，如 以及评估失神经和/或老化恢复的成功 通过嫁接或电刺激获得肌肉。在小组目标1和2中， P-1将提供关于下列人员数量和分布的量化数据 幼年和老年大鼠失神经肌肉纤维上的卫星细胞 以及通过免疫细胞化学方法定位 生肌调节因子家族和蛋白EF-1α和S1。 此外，P-1将从形态上评估移植物的成功。 去神经和衰老的肌肉变成年轻的宿主大鼠。在第三组目标中， P-1将使用卫星细胞分析和分子定位技术 来检验电刺激失神经肌肉的假说 显著降低去神经萎缩的速度和程度。P-1 还将评估刺激失神经移植物的形态 肌肉在检验受刺激-失神经移植物的假说 肌肉恢复情况好于非刺激失神经移植 肌肉。对于目标4组，P-1将评估移植物的形态 已经用快神经或慢神经重新支配的肌肉 幼鼠、成年鼠、老年鼠和极老鼠。这些研究是预期的 为了阐明失神经萎缩的细胞基础和 失神经支配不同时期后的恢复模式 肌肉。这些数据将被用来分析结构和 衰老肌肉的功能缺陷。