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SKELETAL MUSCLE SATELLITE CELL ACIVATION DURING AGING

衰老过程中骨骼肌卫星细胞的激活

基本信息

批准号：
2002088
负责人：
RONALD E ALLEN
金额：
$ 7.51万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 1998-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2002088
关键词：
aging hepatocyte growth factor laboratory rat muscle cells muscle hypertrophy polymerase chain reaction regeneration striated muscles tissue /cell culture

项目摘要

A gradual loss of muscle mass is a common problem afflicting people as they age. Ultimately, this results in diminished strength which predisposes people to injury and may force a change to more restrictive life-styles. The long-range objectives of this project focus on mechanisms responsible for atrophy and suboptimal regeneration of muscle that accompanies aging. Specifically, this work will probe regulation of skeletal muscle satellite cells. These are muscle precursor cells that persist in a quiescent state throughout adult life and are responsible for muscle regeneration and fiber hypertrophy. In order for satellite cells to contribute to muscle repair or growth, they must first be activated from their quiescent state. The process of satellite cell activation is particularly relevant to muscle aging because there is a pronounced delay in activation of quiescent satellite cells in old muscle, and the physiological explanation for this delayed response is not clear. Based on recent research, we hypothesize that hepatocyte growth factor/scatter factor (HGF) is the primary trigger for activating quiescent satellite cells in injured adult muscle. This proposal is designed to investigate the role of HGF in satellite cell activation and the manner in which the activation process may be affected by age. In the proposed experiments, satellite cell culture and whole animal experimental systems will be employed to determine the presence and expression of HGF in rat skeletal muscle as a function of age and injury and to assess the physiological significance of HGF action on satellite cells. The specific aims for this proposal are: (1) to evaluate the presence of HGF in skeletal muscle and to document changes in HGF expression with injury and age, and (2) to evaluate the role of HGF in satellite cell activation in vivo. A thorough understanding of these satellite cell functions will lead to possible strategies for alleviating problems associated with muscle repair and atrophy during aging.

肌肉质量的逐渐丧失是困扰人们的一个常见问题，他们会变老最终，这导致强度减弱，使人们容易受伤，并可能迫使改变更严格的限制，生活方式该项目的长期目标侧重于负责用于伴随衰老的肌肉萎缩和次优再生。具体来说，这项工作将探索骨骼肌卫星的调节细胞这些是肌肉前体细胞，在整个成年生活中，负责肌肉再生，纤维肥大为了让卫星细胞能为肌肉修复或生长，它们必须首先从静止状态激活。卫星细胞激活的过程与以下方面特别相关：肌肉老化，因为有一个明显的延迟激活老年肌肉中静止的卫星细胞及其生理学解释对于这种延迟的反应是不清楚的。根据最近的研究，我们假设肝细胞的生长因子/分散因子（HGF）是激活的主要触发因子。受伤的成年肌肉中静止的卫星细胞。这项建议是旨在研究HGF在卫星细胞活化中的作用，激活过程可能受年龄影响的方式。在建议的实验，卫星细胞培养和整个动物实验系统将用于确定HGF的存在和表达在大鼠骨骼肌中作为年龄和损伤的函数，并评估 HGF对卫星细胞作用的生理意义。该建议的具体目标是：（1）评估在骨骼肌中的HGF，并记录HGF表达的变化，（2）探讨HGF在卫星细胞中的作用体内激活。深入了解这些卫星细胞功能将导致可能的战略，以减轻问题与衰老过程中的肌肉修复和萎缩有关。