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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。肌肉质量和性能的减少，或肌肉减少症，降低了一个人执行日常任务的能力，增加了他们跌倒和跌倒相关伤害的风险。这种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）的减少。虽然研究表明，单肌纤维力的产生和收缩速度随着年龄的增长而减少，但没有报道的研究已经检查了单纤维肌肉性能与年龄相关的递减的分子基础。为了在我们的剥皮单骨骼肌纤维实验中创造尽可能类似于体内的环境，我们建议使用渗透压压缩机Dextran T500，以使肿胀的剥皮晶格间距返回到体内值。BioCAT光束线的使用允许我们使用X射线衍射来测量未结皮纤维的晶格间距，这将近似于体内条件，以及用不同浓度的右旋糖酐T500压缩的结皮纤维，以确定使溶胀的结皮纤维恢复到体内晶格间距值所需的渗透压缩量。基于这些X射线结果，我们将在佛蒙特大学使用使晶格间距恢复到体内值所需的葡聚糖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.