Mechanisms of Neuromuscular Fatigue with Aging

项目总结/摘要 骨骼肌质量下降（肌肉减少症）可导致丧失活动性、独立性 以及进行日常活动的能力，而肌肉疲劳会加剧这一问题。虽然 对等长收缩的研究经常报告说，老年人比年轻人疲劳少， 在动态收缩中通常观察到相反的情况，动态收缩与执行日常活动更相关。 与年龄相关的疲劳性增加和动态过程中肌肉力量损失的机制 收缩是未知的，但必须识别，以帮助改善身体功能和生活质量， 老人本提案的目的是通过以下方式确定老年人疲劳性增加的原因： 整合先进技术，在单个肌纤维水平上研究疲劳（肌肉活检）， 在整个神经肌肉系统（经颅磁刺激）。假设老年人 由于年龄相关的差异，在动态收缩期间， 在肌肉（外周疲劳），而不是在神经系统（中枢疲劳）。研究设计将 还测试了男性和女性以及老年人（60-74岁）和非常老年人（≥75岁）之间肌肉疲劳性的差异 岁）成年人。对老年妇女和老年人的研究有限，但特别重要，因为 同龄人遭受加速的与年龄相关的肌肉质量和功能损失， 肌肉疲劳的有害影响。在目标1中，我将检验以下假设： 动态收缩期间的外周疲劳将导致膝关节的力量和功率的更大降低 与年轻人相比，老年人的伸肌。我会用磁刺激运动皮层 刺激股神经，以测试棘上和外周疲劳的量是否与 年龄或性别在动态疲劳收缩。在目标2中，我将使用从针活检中分离的单纤维 的股外侧肌，以检验老年成人肌纤维收缩效率降低的假设 对肌肉中积累的疲劳代谢物的抑制作用更敏感 与年轻的成年肌肉纤维相比，在动态收缩期间。这些研究将产生一个 全面了解老年人疲劳的原因，将其转化为设计 和测试新的运动干预措施，目标是确定与年龄相关的疲劳机制， 改善老年人的肌肉力量、身体功能和生活质量。

PROJECT SUMMARY/ABSTRACT Age-related declines in skeletal muscle mass (sarcopenia) can result in a loss of mobility, independence and the ability to perform everyday activities, and the problem can be exacerbated by muscle fatigue. Although studies on isometric (static) contractions often report that old adults fatigue less than young adults, the opposite is generally observed in dynamic contractions, which are more relevant for performing daily activities. The mechanisms for the age-related increased fatigability and losses in muscle power during dynamic contractions are not known but are essential to identify to help improve physical function and quality of life in the elderly. The goal of this proposal is to identify the causes for the increased fatigability in old adults by integrating advanced techniques to study fatigue at the level of the single muscle fiber (muscle biopsies) and within the entire neuromuscular system (transcranial magnetic stimulation). The hypothesis is that old adults experience greater fatigue than young adults during dynamic contractions as a result of age-related differences within the muscle (peripheral fatigue) rather than in the nervous system (central fatigue). The study design will also test for differences in muscle fatigability between men and women and old (60-74 yrs) and very old (≥75 yrs) adults. Studies on old women and very old adults are limited but particularly important because both cohorts suffer from accelerated age-related losses in muscle mass and function making them more susceptible to the detrimental effects of muscle fatigue. In Aim 1, I will test the hypothesis that age-related increases in peripheral fatigue during dynamic contractions will result in greater reductions in force and power of the knee extensors in old compared to young adults. I will use magnetic stimulation of the motor cortex and electrical stimulation of the femoral nerve to test whether the amount of supraspinal and peripheral fatigue differs with age or sex during dynamic fatiguing contractions. In Aim 2, I will use single fibers isolated from needle biopsies of the vastus lateralis to test the hypothesis that old adult muscle fibers have a reduced contractile efficiency and are more sensitive to the depressive effects of the fatiguing metabolites that accumulate in the muscle during dynamic contractions compared to young adult muscle fibers. These studies will generate a comprehensive understanding of the causes of fatigue in old men and women that will translate into the design and testing of novel exercise interventions that target the identified mechanisms of age-related fatigability to improve muscle power, physical function and quality of life in the elderly.