Skeletal Muscle Fatigue in Older Adults

描述（由申请人提供）：总体目标是确定肌肉疲劳中年龄相关变化的幅度和机制（最大力产生能力，MVC降低）。阐明年龄对疲劳的影响对老年人的健康和独立生活的维持具有重要意义。我们将研究健康年轻人（20-35岁）和老年人（70-85岁）的踝背屈肌和膝伸肌。肌肉代谢和灌注（1-2年）。用于肌肉工作的ATP通过3种途径合成：肌酸激酶（CK）反应，氧化磷酸化和无氧糖酵解。ATP供应不足会导致疲劳。具体目标I，代谢能力：确定老年肌肉是否表现出产生ATP的能力下降。我们将使用磁共振波谱（MRS）来测量这些通路的能力。假设IA-C：背屈肌将显示A）相似的CK动力学，B）相似的氧化能力，C）老年人的糖酵解速率峰值较低。假设ID-F：膝伸肌将显示D）类似的CK动力学，E）老年人的氧化能力较低，F）老年人的糖酵解速率峰值较低。具体目标2，肌肉灌注：为了检查背屈肌肌力、收缩强度和血流阻塞之间的关系，我们将在一系列等长收缩期间使用功能性MR成像测量年轻人和老年人的反应性充血。假设2A：在充血反应和绝对力之间的双线性关系的交点处，力（N）将不存在年龄差异。假设2B：充血反应和相对力之间关系的交叉点将出现在较高的MVC百分比处。肌肉疲劳（3-5岁）。肌肉群和收缩类型都可能改变衰老中肌肉疲劳研究的结果。具体目标3，疲劳中的肌群特异性：为了确定肌肉和收缩类型对衰老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等长收缩期间的背屈肌和膝伸肌疲劳。我们将测量激活、收缩功能、代谢和充血。假设3A：假设3B：在持续的协议，老年人和年轻人将疲劳相似，并有相同的代谢反应。假设3C：在间歇性方案期间，背屈肌的抗疲劳性的基于年龄的增加幅度大于膝伸肌。具体目标4，疲劳的任务规范特异性（探索性）：在第4年和第5年，我们将1）使用等速收缩测量2个肌肉群的疲劳、激活和收缩功能，2）使用Hill模型研究收缩和系列弹性特性在疲劳中的作用，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.