SINGLE SKELETAL MUSCLE FIBER MECHANICS AND MYOSIN KINETICS IN HUMAN AGING

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。 我们研究的总体、长期目标是在分子水平上研究衰老如何改变人类骨骼肌功能。与年龄相关的肌肉质量和表现的下降，或骨骼减少，会降低一个人执行日常任务的能力，并增加他们摔倒和摔倒相关伤害的风险。功能能力下降的一个关键预测因素是肌肉力量(力量x速度)的下降。尽管已有研究表明单个肌纤维力的产生和收缩速度随着年龄的增长而降低，但还没有报道研究与年龄相关的单纤维肌肉性能下降的分子基础。为了在我们的皮肤单一骨骼肌纤维实验中创造尽可能类似于体内的环境，我们建议使用渗透性压缩机葡聚糖T500，将膨胀的皮肤晶格间距恢复到体内的值。通过使用BioCAT光束线，我们可以使用X射线衍射来测量未剥皮纤维以及用不同浓度的葡聚糖T500压缩的有皮纤维的晶格间距，以确定将膨胀的有皮纤维恢复到体内晶格间隔值所需的渗透压缩量。基于这些X射线结果，我们将在佛蒙特州大学使用将晶格间距恢复到活体数值所需的葡聚糖T500浓度进行单纤维测量。

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. The overall, long-term goal of our research is to examine how aging alters skeletal muscle function in humans at the molecular level. Age-related reductions in muscle mass and performance, or sarcopenia, decrease a person's ability to perform everyday tasks and increase their risk of falling and fall-related injuries. A key predictor of this decrease in functional capacity is a reduction in muscle power (force x velocity). Although studies have shown that single muscle fiber force production and contractile velocity are reduced with age, no reported study has examined the molecular basis of the age-related decrements in single fiber muscle performance. In order to create an environment as similar to in vivo as possible in our skinned single skeletal muscle fiber experiments, we propose to use an osmotic compressor, Dextran T500, to return the swollen skinned lattice spacing back to in vivo values. Use of the BioCAT beam line allowed us to use x-ray diffraction to measure the lattice spacing of unskinned fibers, which would approximate in vivo conditions, as well as skinned fibers compressed with different concentrations of Dextran T500 to determine the amount of osmotic compression necessary to return the swollen skinned fibers to in vivo lattice spacing values. Based on these x-ray results, we will perform our single fiber measurements at the University of Vermont using the concentration of Dextran T500 necessary to return the lattice spacing to in vivo values.