SINGLE SKELETAL MUSCLE FIBER MECHANICS AND MYOSIN KINETICS IN HUMAN AGING

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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.