MUSCLE BIOPSY FRAIL VS NON-FRAIL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管脆弱很难定义，但弗里德和她的同事们已经根据身体和心理特征建立了脆弱的标准。这些特征包括非故意的体重减轻(每年10磅或更多)，自我报告的疲惫，以握力衡量的虚弱，缓慢的行走速度，以及低体力活动(Fry等人，2001)。有了一个检查虚弱的框架，我们建议更全面地探索虚弱和非虚弱老年人的石棺减少的病理生理学。在Frontera等人中。2000年和Balagopal等人。1997年，作者假设肌纤维减少的主要原因是肌丝格子内功能失调的收缩蛋白的替代能力降低。利用二次谐波成像显微镜(SHIM)中的信号，这种信号来自肌肉肌节内收缩蛋白质的局部密度和排列，并对其敏感，这种新的非线性激光扫描显微镜模式将允许对完全天然、完整的肌肉组织的组织学和分子结构进行定量分析。到目前为止，很少有研究提供对高龄个体肌肉的广泛和定量的超微结构检查(Frontera等人。2000)。Fiatarone Singh及其同事报告了使用电子显微镜概述虚弱老年人肌肉损伤方面的数据，与Shim相比有局限性。

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. Although frailty has been difficult to define, Fried and her colleagues have established criteria for frailty based on physical ad psychological characteristics. These characteristics include unintentional weight loss (10 or more pounds per year), self-reported exhaustion, weakness as measured by grip strength, slow walking speed, and low physical activity (Fried et al., 2001). With a framework to examine frailty, we propose to explore more fully the pathophysiology of sarcopenia in frail and non-frail older individuals. In Frontera et al. 2000 and Balagopal et al. 1997, the authors hypothesized that sarcopenia largely results from the decreased ability for the replacement of dysfunctional contractile proteins within the myofilament lattice. Exploiting the signal in Second Harmonic Imagine Microscopy (SHIM), which is derived from and sensitive to the local density and alignment of contractile proteins within muscle sarcomeres, this new mode of non-linear laser-scanning microscopy will allow quantitative analysis of both the histology and molecular structure of completely native, intact muscle tissue. Thus far, few studies to date have provided extensive and quantitative ultrastructural examination of muscle from very old individuals (Frontera et al. 2000). Fiatarone Singh and colleagues, reported data outlining aspects of muscle damage in frail elders using electron microscopy, which has limitations in comparison to SHIM.