Mechanisms of Skeletal Muscle Fatigue in Aging Adults

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DESCRIPTION (provided by applicant): The impact of old age on the magnitude and mechanisms of human skeletal muscle fatigue is not well understood. The candidate's long-term goal is to continue to contribute important new information about the effects of old age on muscle function, with particular reference to how sex and habitual physical activity may alter age-related changes in fatigue. This application is designed to complement the Pl's new R01 "Skeletal Muscle Fatigue in Older Adults." This career development award will allow the candidate to focus more fully on developing the depth and breadth of her research program, by providing release time from teaching responsibilities. Career development activities will comprise three main components: 1) enhancement of state-of-the-art magnetic resonance spectroscopy and imaging expertise, 2) development of expertise and new noninvasive methodologies for measuring skeletal muscle perfusion, and 3) strengthening of statistical design, analysis and interpretation knowledge relevant to this line of research. Collaborations with leading investigators on-campus (John Buonaccorsi, PhD) and at Yale University (Douglas Rothman, PhD) and JB Pierce Foundation (Steven Segal, PhD) will be fostered and strengthened during this period. The candidate will develop a new seminar series related to the training of graduate students and postdocs in the Responsible Conduct of Research. These activities will ensure the candidate's continued high level of productivity and enable the development of additional integrative research projects in this area. The Specific Aims of the Research Project are: 1) Metabolic Capacity: to determine whether older skeletal muscle exhibits a decreased capacity to produce ATP for energy in vivo; 2) Muscle Perfusion: to examine the relationships between ankle dorsiflexor muscle strength, contraction intensity and occlusion of blood flow; 3) Muscle Group Specificity in Fatigue: to determine the impact of muscle (knee extensors vs. dorsiflexors) and contraction type (intermittent vs. sustained) on the extent and mechanisms of fatigue in young and older adults; 4) Task Specificity in Fatigue: to investigate how task (isometric vs. dynamic contractions) affects the extent and mechanisms of fatigue in young and older men and women. Nonivasive measures of muscle activation, perfusion, metabolism and contractile function will be made using magnetic resonance spectroscopy and functional imaging, electromyography and electrical stimulation.