SINGLE SKELETAL MUSCLE FIBER MECHANICS AND MYOSIN KINETICS IN HUMAN AGING

人类衰老过程中的单骨骼肌纤维力学和肌球蛋白动力学

• 批准号: 8166995
• 负责人: MARK Steven MILLER
• 金额: $ 2.14万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166995
• 关键词: Actins; Activities of Daily Living; Aerobic Exercise; Age; Aging; Anesthesia procedures; Area; Biopsy; Blood Chemical Analysis; Blood specimen; Body Composition; Body fat; Cardiac; Clinical Research; Coagulation Process; Computer Retrieval of Information on Scientific Projects Database; Depressed mood; Elderly; Elderly man; Electrocardiogram; Exercise; Exercise stress test; Fatty acid glycerol esters; Funding; Goals; Grant; Health; Health Transition; Heart Diseases; Hormonal; Human; Injury; Institution; Isometric Exercise; Isotonic Exercise; Joints; Kidney; Kinetics; Knee; Left; Lidocaine; Liver; Measurement; Measures; Mechanics; Medical; Mental Health; Molecular; Monitor; Muscle; Muscle Fibers; Muscle function; Myosin ATPase; Outcome; Outpatients; Pain; Performance; Persons; Physical Function; Population; Procedures; Production; Proteins; Protocols documentation; Questionnaires; Rehabilitation Centers; Reporting; Research; Research Personnel; Resources; Rest; Role; Skeletal Muscle; Social Functioning; Source; Structure; Testing; Thigh structure; Tissue Banks; Tissues; United States National Institutes of Health; Universities; Vermont; Visit; Woman; X-Ray Computed Tomography; age effect; age related; base; fall risk; falls; human subject; muscle form; muscle strength; sarcopenia; standard measure; vastus lateralis; volunteer

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们研究的总体长期目标是研究衰老如何在分子水平上改变人类骨骼肌功能。本提交的目的是获得批准对年轻（21-35 岁，n=24）和老年（65-75 岁，n=24）志愿者进行肌肉功能测量，以完成 NIH K01 资助的两个目标。 1) 目标（NIH K01 资助的具体目标）： 与年龄相关的肌肉质量和性能下降或肌少症会降低一个人执行日常任务的能力，并增加跌倒和跌倒相关伤害的风险。功能能力下降的一个关键预测因素是肌肉力量（力 x 速度）的下降。尽管研究表明单肌纤维产生的力量和收缩速度会随着年龄的增长而降低，但没有研究报告研究单纤维肌肉性能与年龄相关的下降的分子基础。我们开发了将正弦分析应用于人类骨骼肌纤维的协议和技术平台，从而可以检查年龄对肌球蛋白-肌动蛋白跨桥水平的单肌纤维动力学和结构的影响。我们的假设是，衰老通过抑制肌球蛋白动力学参数和减少肌球蛋白蛋白质含量来降低收缩功能。我们将通过检查年轻和老年男性和女性大腿肌肉（股外侧肌）的单一骨骼肌纤维功能来检验这一假设。 2) 涉及人类受试者的程序： 以下程序将在佛蒙特大学普通临床研究中心 (GCRC) 或心脏康复中心的两次（年轻）或三次（老年）门诊就诊期间进行： 肌肉力量测试 - 将使用多关节测力计在等长和等速条件下测试膝伸肌的收缩性能。 运动压力测试 - 将在跑步机运动期间测量有氧运动能力。 身体成分分析 - 通过双能 X 射线吸收测定法测量全身脂肪和无脂肪组织质量，以确定全身瘦组织质量和四肢肌肉质量。大腿肌肉横截面积将通过计算机断层扫描测量。 心电图 - 将进行静息心电图检查以测试心脏病的体征，并在运动测试期间对老年人进行检查以监测心脏功能。 血液样本 - 将采集血液样本来测量标准血液化学、计数（CBC w/diff）和肝/肾/激素功能，并根据 GCRC 对接受肌肉活检程序的任何志愿者的要求确定凝血能力（PT/PTT）。 肌肉组织采集 - 将在利多卡因麻醉下对左右大腿（股外侧肌）进行经皮活检。 以下程序将由 GCRC 之外的志愿者执行： 问卷 - 将完成医疗结果简式问卷 (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、心理健康和报告的健康转变。 活动监测器 - 一个小型加速计将被固定在受试者裤子的腰带上 7 天，以监测活动水平。