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。本意见书的目的是获得批准，对年轻(21-35岁，n=24)和老年(65-75岁，n=24)志愿者群体进行肌肉功能测量，以完成NIH K01基金资助的两个目标。 1)目标(NIH K01补助金的具体目标)： 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。我们已经开发了将正弦分析应用于人类骨骼肌纤维的方案和技术平台，从而可以在肌球蛋白-肌动蛋白跨桥的水平上检查年龄对单个肌肉纤维动力学和结构的影响。我们的假设是，衰老通过降低肌球蛋白动力学参数和减少肌球蛋白蛋白含量来降低收缩功能。我们将通过检测年轻和老年男性和女性的大腿肌肉(股外侧肌)的单一骨骼肌纤维功能来检验这一假设。 2)涉及人体受试者的程序： 以下程序将在佛蒙特州大学综合临床研究中心(GCRC)或心脏康复中心的两次(年轻)或三次(老年)门诊就诊期间执行： 肌肉力量测试-将使用多关节测功器在等长和等速条件下测试膝关节伸肌的收缩性能。 运动负荷测试-有氧运动能力将在跑步机运动中进行测量。 身体成分分析-全身脂肪和脱脂组织质量将通过双能X射线吸收法测量，以确定全身瘦组织质量和附件肌肉质量。大腿肌肉横截面积将由计算机断层扫描测量。 心电图-静息心电图将被用来测试心脏病的迹象，并将在运动测试期间对老年人进行检查，以监测心脏功能。 血样-将根据GCRC对任何接受肌肉活检程序的志愿者的要求，采集血样以测量标准血液化学、计数(CBC w/diff)和肝/肾/激素功能，并确定凝血能力(PT/PTT)。 肌肉组织采集-将在利多卡因麻醉下对右侧和左侧大腿(股外侧肌)进行经皮活检。 以下程序将由GCRC以外的志愿者执行： 问卷-将完成一份医疗结果简明问卷(MOS-SF-36)，该问卷测量8个领域，包括身体功能、角色功能、身体疼痛、一般健康、活力、社会功能、精神健康和报告的健康转变。 活动监测器--一个小的加速度计将被固定在受试者的裤腰上7天，以监测他们的活动水平。

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. The purpose of this submission is to obtain approval to perform muscle function measurements on a population of young (21-35 yrs old, n=24) and elderly (65-75 yrs old, n=24) volunteers in order to complete two goals of a funded NIH K01 grant. 1) Objectives (Specific Aims of the NIH K01 Grant): 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. We have developed protocols and technological platforms to apply sinusoidal analysis to human skeletal muscle fibers that allow examination of the effect of age on single muscle fiber kinetics and structure at the level of the myosin-actin cross-bridge. Our hypothesis is that aging reduces contractile function by depressing myosin kinetic parameters and reducing myosin protein content. We will test this hypothesis by examining single skeletal muscle fiber function of the thigh muscle (vastus lateralis) in young and elderly men and women. 2) Procedures involving human subjects: The following procedures will be performed during two (young) or three (elderly) out-patient visits to the University of Vermont General Clinical Research Center (GCRC) or Cardiac Rehabilitation Center: Muscle Strength Testing - The contractile performance of the knee extensor muscles will be tested under isometric and isokinetic conditions using a multi-joint dynamometer. Exercise Stress Test - Aerobic exercise capacity will be measured during treadmill exercise. Body Composition Analysis - Whole body fat and fat-free tissue mass will be measured by dual energy x-ray absorptiometry to determine whole body lean tissue mass and appendicular muscle mass. Thigh muscle cross-sectional area will be measured by computed tomography. Electrocardiogram - Resting ECG will be performed to test for signs of heart disease and will be performed on the elderly during the exercise test to monitor cardiac function. Blood Samples - Blood samples will be taken to measure standard blood chemistry, counts (CBC w/diff), and liver/kidney/hormonal function and to determine clotting ability (PT/PTT) per the GCRC's requirement of any volunteer undergoing the muscle biopsy procedure. Muscle Tissue Collection - Percutaneous biopsies of the right and left thigh (vastus lateralis) will be performed under lidocaine anesthesia. The following procedures will be performed by volunteers outside of the GCRC: Questionnaires - A Medical Outcomes Short Form Questionnaire (MOS-SF-36) which measures 8 domains, including physical functioning, role functioning, bodily pain, general health, vitality, social functioning, mental health and reported health transition, will be completed. Activity monitor - A small accelerometer will be attached to the subject's waistband of their pants for 7 days to monitor activity level.