This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this submission is to obtain approval to perform measurements on a small number of young volunteers in order to obtain preliminary data for a NIH K01 grant re-submission. The data from these measurements will be used to further demonstrate operational feasibility of the sinusoidal length perturbation technique, to buttress our hypothesis that aging alters single muscle fiber mechanics/kinetics and for determining appropriate sample sizes for young and elderly populations. These data are required because this technique has never before been performed on young human skeletal muscle tissue. Application of this technique to human tissue was made possible by recent equipment and technical innovations developed in our laboratories. It is important to note that we have all of the techniques available to complete the sinusoidal analysis, as demonstrated in the attached grant application (pg 51-52 and 54-57). Four young, healthy human subjects (2 men/2 women) are needed for this preliminary study. Preliminary data for a similar number of elderly subjects will be obtained from muscle fibers obtained from elderly volunteers in Dr. Toth's on-going study entitled 'Skeletal muscle contractile dysfunction in heart failure' (CHRMS# 06-150). Dr. Toth routinely performs sinusoidal analysis on these volunteer's fibers as part of his approved protocol, as well as body composition and muscle strength measurements.
Specific Aims of the NIH K01 Grant:Age-related reductions in muscle mass and performance, or sarcopenia, decreases the ability of elderly people to perform day-to-day tasks and increases their risk of falling and incurring fall-related injuries. A key predictor of this decrease in functional capacity is a reduction in muscle power. While whole muscle studies indicate force and velocity decrease with age, the molecular mechanisms underlying the loss of performance remain to be elucidated. Here, we propose to use sinusoidal analysis, a powerful technique not yet used on human skeletal muscle fibers, to determine the effect of age on single muscle fiber mechanics and kinetics at the level of the myosin-actin cross-bridge. Our general hypothesis is that aging reduces the capacity of single fibers to produce power 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. A full accounting of the aims and hypotheses for the project proposed to NIH is provided in the attached grant application.Procedures Involving Human Subjects:The following prodedures will be performed during two, brief out-patient visits to the University of Vermont General Clinical Research Center (GCRC): Muscle Strength Testing - The contractile performance of the knee extensor muscles will be tested isometrically and isokinetically using a multi-joint dynamometer.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.Blood Sample - A blood sample will be taken to measure blood count and determine clotting ability per the GCRC's requirement of any volunteer undergoing the muscle biopsy procedure.Muscle Tissue Collection - A percutaneous biopsy of the right thigh (vastus lateralis) will be performed under lidocaine anesthesia.
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