Skeletal Muscle Fatigue in Older Adults

描述（由申请人提供）：人体骨骼肌在一段时间内做功的能力对于维持健康和身体功能至关重要。在老年，神经肌肉系统发生了深刻的变化，其中许多变化因废用而加剧。在这个项目中，我们将继续追求我们的长期目标，即通过整合神经，收缩和代谢功能的测量来阐明老年人骨骼肌疲劳的机制和影响，以测试与老年肌肉产生能量和力量的能力相关的新假设。与此同时，我们将提供有关老年人疲劳（定义为最大力量产生能力的下降）的新信息，这些老年人具有身体功能受损的早期迹象。我们的具体目标是确定：1）年龄和身体损伤对肌肉代谢经济的神经和肌肉成分的影响，以及2）年龄和身体损伤对肌肉疲劳机制的影响。为了实现我们的目标，我们将使用一种综合方法，在这种方法中，我们测量肌肉的神经信号，肌肉提供能量的能力，以及保持剧烈收缩的能力。这套独特的研究将使用最先进的方法进行，包括留置电极和非侵入性磁共振波谱和成像。使用横截面设计，我们将比较肌肉疲劳的程度和机制，同时考虑我们研究对象的体力活动水平和身体功能的差异。在这个为期4年的项目中，我们将研究年轻（21-35岁）和老年（65-80岁）健康和行动不便的男性和女性的踝关节背屈肌。背屈肌为计划中的研究提供了一个很好的模型，它们对胜任运动特别重要。该项目将提供一个独特的知识体系，了解神经和代谢因素如何介导一系列老年受试者的抗疲劳性与年龄相关的变化。我们将解决长期存在的差距，在我们的理解如何神经，收缩和代谢系统整合，以调节年轻人和老年人的神经肌肉功能，以及如何整合可能会与老年人的身体表现下降中断。牙髓健康相关性：神经肌肉系统的年龄相关变化是深刻的。尽管神经肌肉系统对老年人的健康和独立至关重要，但支持身体功能的神经，能量和肌肉因素之间的相互作用和调节目前尚不清楚。通过解决这些知识的关键差距，我们将应对老年医学研究中的两个重要优先事项：1）我们将确定健康和身体受损的老年人对肌肉工作的“压力源”的反应能力，以及2）我们将在损伤-残疾-虚弱级联中相对较早地识别潜在的“虚弱的可预防方面”。

DESCRIPTION (provided by applicant): The ability of human skeletal muscle to perform work over a period of time is critical to the maintenance of health and competent physical functioning. In old age, there are profound changes that occur in the neuromuscular system, many of which are exacerbated by disuse. In this project we will continue pursuit of our long-term goal of elucidating the mechanisms and impact of skeletal muscle fatigue in aging humans by integrating measures of neural, contractile and metabolic function to test novel hypotheses related to the ability of old muscle to produce energy and force. At the same time, we will provide new information about fatigue (defined as the fall of maximal force-generating capacity) in older adults with early signs of impaired physical function. Our Specific Aims are to determine the effects of: 1) old age and physical impairment on the neural and muscular components of muscle metabolic economy, and 2) age and physical impairment on the mechanisms of muscle fatigue. To accomplish our goals, we will use an integrative approach in which we measure the neural signals to the muscle, the ability of the muscle to provide energy, and its capacity to maintain vigorous contractions. This unique set of studies will be conducted using state-of-the-art methodologies, including in-dwelling electrodes and non-invasive magnetic resonance spectroscopy and imaging. Using a cross-sectional design, we will compare the magnitude and mechanisms of muscle fatigue, while accounting for differences in physical activity level and physical functioning in our study subjects. Over the course of this 4-year project, we will study the ankle dorsiflexor muscles of young (aged 21-35 years) and older (65-80) healthy and mobility-impaired men and women. The dorsiflexors provide an excellent model for the planned studies, and they are particularly important to competent locomotion. This project will provide a unique body of knowledge about how neural and metabolic factors may mediate age-related changes in fatigue resistance in a range of older subjects. We will address the long-standing gap that exists in our understanding of how the neural, contractile and metabolic systems are integrated to regulate neuromuscular function in young and older adults, and how that integration may be disrupted with the decline in physical performance in the elderly. PULBIC HEALTH RELEVANCE: The age-related changes in the neuromuscular system are profound. Despite the vital importance of the neuromuscular system to health and independence in old age, the interactions between and regulation of the neural, energetic and muscular factors that support competent physical functioning are not clear at this time. By addressing these key gaps in knowledge, we will respond to two important priorities in geriatric research: 1) we will determine the ability of both healthy and physically-impaired older adults to "respond to the stressor" of muscular work, and 2) we will identify potential "preventable aspects of frailty" relatively early in the impairment-disability-frailty cascade.