Mechanisms of Skeletal Muscle Fatigue in Aging Adults

描述（由申请人提供）：老年对人体骨骼肌疲劳程度和机制的影响尚未得到充分了解。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，特别是关于性别和习惯性体力活动如何改变与年龄相关的疲劳变化。此应用程序的目的是补充PI的新R 01“在老年人的骨骼肌疲劳。“这个职业发展奖将允许候选人更充分地专注于发展她的研究计划的深度和广度，通过提供教学责任的释放时间。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非侵入性方法，以及3）加强与该研究相关的统计设计，分析和解释知识。在此期间，将促进和加强与校园内（John Buonaccorsi，博士）和耶鲁大学（道格拉斯罗斯曼，博士）以及JB皮尔斯基金会（Steven Segal，博士）的主要研究人员的合作。候选人将开发一个新的研讨会系列相关的研究生和博士后在负责任的研究行为的培训。这些活动将确保候选人的持续高水平的生产力，并使更多的综合研究项目在这一领域的发展。 研究项目的具体目的是：1）代谢能力：确定老年骨骼肌是否表现出体内产生ATP能量的能力下降; 2）肌肉灌注：检查踝背屈肌肌力、收缩强度和血流阻塞之间的关系; 3）疲劳时的肌群特异性：来确定肌肉的影响（膝伸肌与背屈肌）和收缩类型（间歇性与持续性）对年轻人和老年人疲劳程度和机制的影响; 4）疲劳的任务特异性：研究任务（等长收缩与动态收缩）如何影响年轻和老年男性和女性的疲劳程度和机制。将使用磁共振波谱和功能成像、肌电图和电刺激对肌肉激活、灌注、代谢和收缩功能进行无创测量。

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.