MUSCLE DISUSE AND CONTRACTILE DYSFUNCTION IN THE ELDERLY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 骨骼肌停用是导致老年人残疾的一个重要因素。老年人更有可能经历废用，更容易受到其衰弱效应的影响，因为他们的生理储备减少了。尽管有这些事实，但在这一人群中，停用促进骨骼肌收缩功能障碍的细胞和分子机制仍未得到很大程度的研究。在最近对美国国立卫生研究院的拨款申请中，我们建议通过研究终末期双侧骨关节炎患者，系统地测试骨骼肌纤维结构和功能的改变，这些结构和功能是老年人废用相关收缩功能障碍的基础。具体地说，我们将把这些患者的数据与活动水平正常的健康老年对照组进行比较。我们假设，老年人的肌肉停用通过改变肌球蛋白跨桥动力学、肌丝蛋白含量和肌丝格子的力学性质来损害单个肌纤维的收缩功能。在赠款申请中，我们建议评估患者的腿部肌肉力量(测力)、整体和局部身体成分(放射成像技术：双能X射线吸收法和CT)、体力活动水平(加速计)，并通过经皮活组织检查从大腿肌肉(股外侧肌)获取组织。在这份意见书中，我们请求允许对4名骨关节炎患者进行研究，以便为拨款申请获得初步数据。这些数据可以在审查申请前两周内发送给NIH。这将是证明我们招募和测试骨关节炎患者的能力的重要数据，并可以提供数据支持我们关于停用对肌肉收缩功能的影响的假设。在这4名患者中，我们将进行肌肉力量(测力)、身体成分(双能X射线吸收法)、体力活动(1wk加速度计)的评估，并通过肌肉活检获取组织。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Skeletal muscle disuse is an important contributing factor to disability in the elderly. Elderly individuals are more likely to experience disuse and are more susceptible to its debilitating effects because of their diminished physiological reserve. Despite these facts, the cellular and molecular mechanisms whereby disuse promotes skeletal muscle contractile dysfunction in this population remain largely unstudied. In a recent grant application to NIH, we proposed to systematically test for modifications of skeletal muscle fiber structure and function that underlie disuse-related contractile dysfunction in elderly humans by studying patients with end-stage, bilateral osteoarthritis. Specifically, we will compare data from these patients to healthy elderly controls with normal activity levels. We hypothesize that muscle disuse in the elderly impairs single muscle fiber contractile function through alterations in acto-myosin cross-bridge kinetics, myofilament protein content and the mechanical properties of the myofilament lattice. In the grant application, we propose to assess patients for leg muscle strength (dynamometry), total and regional body composition (radiologic imaging techniques: dual-energy x-ray absorptiometry and CT), physical activity levels (accelerometer) and obtain tissue from the thigh muscle (vastus lateralis) via percutaneous biopsy. In this submission, we are requesting permission to study 4 patients with osteoarthritis in order to obtain preliminary data for the grant submission. This data can be sent to NIH up to 2 wks prior to the review of the application. This will be important data to demonstrate our ability to recruit and test osteoarthritis patients and could provide data to support our hypotheses regarding the effects of disuse on muscle contractile function. In these 4 patients, we will perform assessments of muscle strength (dynamometry), body composition (dual-energy x-ray absorptiometry), physical activity (accelerometery for 1 wk) and obtain tissue via muscle biopsy.