MUSCLE BIOPSY FRAIL VS NON-FRAIL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管虚弱很难定义，弗里德和她的同事已经根据身体和心理特征建立了虚弱的标准。这些特征包括无意的体重减轻（每年10磅或更多），自我报告的疲惫，通过握力测量的虚弱，缓慢的行走速度和低体力活动（Fried et al., 2001）。在检查虚弱的框架下，我们建议更充分地探索虚弱和非虚弱老年人肌肉减少症的病理生理学。在Frontera et al. 2000和Balagopal et al. 1997中，作者假设肌肉减少症主要是由于肌丝晶格内功能失调的收缩蛋白的替代能力下降。利用二次谐波想象显微镜（SHIM）的信号，该信号来源于并敏感于肌肉肌瘤内的局部密度和收缩蛋白的排列，这种非线性激光扫描显微镜的新模式将允许对完全天然的完整肌肉组织的组织学和分子结构进行定量分析。迄今为止，很少有研究对高龄个体的肌肉进行广泛和定量的超微结构检查（Frontera et al. 2000）。Fiatarone Singh和他的同事用电子显微镜报告了虚弱老年人肌肉损伤方面的数据，与SHIM相比，电子显微镜有局限性。

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.