Mechanisms of Skeletal Muscle Fatigue in Aging Adults

描述（由申请人提供）：老年对人类骨骼肌疲劳程度和机制的影响尚不清楚。候选人的长期目标是继续提供有关老年对肌肉功能影响的重要新信息，特别是关于性和习惯性体育活动如何改变与年龄相关的疲劳变化。该应用程序旨在补充Pl的新R01“老年人骨骼肌疲劳”。这个职业发展奖项将使候选人能够更充分地专注于发展她的研究项目的深度和广度，并提供从教学职责中解放出来的时间。职业发展活动将包括三个主要组成部分：1)增强最先进的磁共振光谱和成像专业知识；2)开发测量骨骼肌灌注的专业知识和新的无创方法；3)加强与这一研究方向相关的统计设计、分析和解释知识。在此期间，将促进和加强与校园（John Buonaccorsi博士）、耶鲁大学（Douglas Rothman博士）和JB Pierce基金会（Steven Segal博士）的主要研究人员的合作。该候选人将开发一个与培养研究生和博士后负责任研究行为相关的新系列研讨会。这些活动将确保候选人保持高水平的生产力，并使其能够在该领域开展更多的综合研究项目。

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.