Skeletal Muscle Fatigue in Older Adults

描述(由申请人提供)：总体目标是确定与年龄相关的肌肉疲劳变化的幅度和机制(最大力量生成能力下降)。阐明年龄对疲劳的影响对于健康和在衰老中维持独立生活具有重要的意义。我们将研究健康年轻人(20-35岁)和老年人(70-85岁)的脚踝背屈肌和膝关节伸肌。肌肉代谢和灌流(1-2岁)。肌酸激酶(CK)反应、氧化磷酸化和厌氧糖酵解是肌动蛋白合成的3条途径。ATP供应不足会导致疲劳。特定目标I，新陈代谢能力：确定老年肌肉是否表现出产生ATP的能力降低。我们将使用磁共振波谱(MRS)来测量这些通路的容量。假设IA-C：在老年人中，多指屈肌表现出A)相似的CK动力学，B)相似的氧化能力，C)较低的峰值糖酵解率。假设ID-F：膝关节伸肌将表现出D)相似的CK动力学，E)老年人较低的氧化能力，F)老年人较低的糖酵解率。特定目标2，肌肉灌流：为了研究背屈肌力、收缩强度和血流闭塞之间的关系，我们将使用功能磁共振成像技术测量年轻人和老年人在一系列等长收缩过程中的反应性充血。假设2A：在充血反应和绝对力之间的双线性关系的交点处的力(N)不会因年龄而异。假设2B：充血反应和相对力量之间的关系的交集将发生在MVC的较高百分比。肌肉疲劳(3-5岁)。肌肉群和收缩类型都可能改变衰老过程中肌肉疲劳的研究结果。具体目标3，肌肉群在疲劳中的特异性：为了确定肌肉和收缩类型对衰老过程中疲劳程度和机制的影响，我们将比较最大间歇性和最大持续性等长收缩时的背屈和伸膝疲劳，我们将测量激活、收缩功能、代谢和充血。假设3A：在间歇性训练中，老年人的疲劳程度较低，肌肉酸碱度的下降也较少。假设3B：在持续的治疗方案中，老年人和年轻人会有类似的疲劳，并有相同的新陈代谢反应。假设3C：与膝关节伸肌相比，间歇性训练中背屈肌疲劳耐力随年龄增长的幅度更大。具体目标4，任务规范在疲劳中的特异性(探索性)：在第4年和第5年，我们将1)使用等速收缩来测量两组肌肉的疲劳、激活和收缩功能，2)使用Hill模型来研究收缩和系列弹性特性在疲劳中的作用，以及3)开发在MRS系统中进行动态疲劳研究的方法。

DESCRIPTION (provided by applicant): The overall goal is to determine the magnitude and mechanisms of age-related changes in muscle fatigue (decrease in maximal force-generating capacity, MVC). Clarification of the influence of age on fatigue has important implications for health and the maintenance of independent living in aging. We will study the ankle dorsiflexor and knee extensor muscles of healthy young (20-35 yrs) and older (70-85 yrs) adults. Muscle Metabolism and Perfusion (Years 1-2). ATP for muscular work is synthesized by 3 pathways: the creatine kinase (CK) reaction, oxidative phosphorylation and anaerobic glycolysis. Inadequate ATP supply can result in fatigue. Specific Aim I, Metabolic Capacity: To determine whether older muscle exhibits a decreased capacity to produce ATP. we will use magnetic resonance spectroscopy (MRS) to measure the capacities of these pathways. Hypotheses IA-C: Dorsiflexors will show A) similar CK kinetics, B) similar oxidative capacities, C) lower peak glycolytic rates in older adults. Hypotheses ID-F: Knee extensors will show D) similar CK kinetics, E) lower oxidative capacity in older, F) lower peak glycolytic rates in older adults. Specific Aim 2, Muscle Perfusion: To examine the relationships between dorsiflexor muscle strength, contraction intensity and blood flow occlusion, we will measure the reactive hyperemia of young and older adults using functional MR imaging during a series of isometric contractions. Hypothesis 2A: There will be no difference by age in the force (N) at the intersection of the bilinear relationship between the hyperemic response and absolute force. Hypothesis 2B: The intersection of the relationship between the hyperemic response and relative force will occur at a higher percentage of MVC. Muscle Fatigue (Years 3-5). Both muscle group and type of contraction may alter the outcome in studies of muscle fatigue in aging. Specific Aim 3, Muscle Group Specificity in Fatigue: To determine the impact of muscle and contraction type on the extent and mechanisms of fatigue in aging, we will compare dorsiflexor and knee extensor fatigue during maximal intermittent and maximal sustained isometric contractions We will measure activation, contractile function, metabolism and hyperemia. Hypothesis 3A: During the intermittent protocols, older will fatigue less and show less decrease in muscle pH. Hypothesis 3B: During the sustained protocols, older and young will fatigue similarly and have the same metabolic response. Hypothesis 3C: The magnitude of the age-based increase in fatigue resistance during the intermittent protocol will be greater in the dorsiflexors compared to the knee extensors. Specific Aim 4, Task Spec Specificity in Fatigue (Exploratory): In Years 4 and 5, we will 1) measure fatigue, activation and contractile function in the 2 muscle groups using isovelocity contractions, 2) use the Hill Model to investigate the role of contractile and series elastic properties in fatigue, and 3) develop methods to perform dynamic fatigue studies in the MRS system.