Skeletal Muscle Fatigue in Older Adults

描述(由申请人提供)：人类骨骼肌在一段时间内执行工作的能力对维持健康和胜任的身体功能至关重要。在老年，神经肌肉系统会发生深刻的变化，其中许多变化会因不使用而加剧。在这个项目中，我们将继续追求我们的长期目标，通过整合神经、收缩和代谢功能的测量来测试与老年肌肉产生能量和力量的能力相关的新假说，来阐明老年人类骨骼肌疲劳的机制和影响。与此同时，我们将提供有关疲劳(定义为最大力量产生能力下降)的新信息，这些老年人早期有身体功能受损的迹象。我们的具体目标是确定：1)老年和身体损伤对肌肉代谢经济的神经和肌肉成分的影响；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的方法，测量肌肉的神经信号，肌肉提供能量的能力，以及它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，包括室内电极和非侵入性磁共振波谱和成像。使用横断面设计，我们将比较肌肉疲劳的程度和机制，同时考虑到我们研究对象的身体活动水平和身体功能的差异。在这个为期四年的项目中，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脚踝背屈肌。背屈肌为计划中的研究提供了一个很好的模型，而且它们对有能力的运动尤为重要。这个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在一系列老年受试者中调节与年龄相关的疲劳抵抗力的变化。我们将解决长期存在的差距，我们的理解存在于如何整合神经、收缩和代谢系统来调节年轻人和老年人的神经肌肉功能，以及这种整合可能如何随着老年人身体表现的下降而中断。牙髓健康相关性：神经肌肉系统中与年龄相关的变化是深刻的。尽管神经肌肉系统对老年人的健康和独立性至关重要，但支持良好身体功能的神经、能量和肌肉因素之间的相互作用和调节目前尚不清楚。通过解决这些关键的知识差距，我们将回应老年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做出反应的能力；2)我们将在损伤-残疾-脆弱级联中相对较早地识别潜在的“可预防的脆弱方面”。

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.