Fatigability of Limb Muscle in Older Adults: Protective Effects of Exercise

 描述（由申请人提供）：老年人进行日常活动的能力受到肌肉质量损失（肌肉减少症）和动力降低的影响，并且肌肉疲劳的发展加剧了该问题。该提案将通过研究老年男性和女性（≥ 70岁）动态收缩引起的疲劳来解决这些问题。我们采取了一种翻译的方法，通过检查疲劳的机制，从动态收缩的单纤维（从肌肉活检），整个肌肉（磁共振波谱，MRS）和神经肌肉系统内（使用经颅磁刺激，TMS）。该假说认为，在动态收缩过程中，老年人比年轻人更快地疲劳，这是由于骨骼肌纤维固有的与年龄相关的效率低下（外周疲劳），而不是中枢神经系统的更大疲劳（中枢疲劳）。我们的实验设计包括对男性和女性的全面研究，以检查性别差异。这一点特别重要，因为认识到尽管老年妇女更容易疲劳，但老年妇女的疲劳却很少受到关注。第二个目标是测试一种新的运动模式，以保护老年人免受疲劳。该假设是，以已知引起峰值功率的速度和力量进行缓慢的六秒缩短和六秒延长收缩的训练将在更大程度上改善老年人的整个肌肉和身体性能，肌纤维尺寸和功能，而不是传统的高阻力（一次最大充盈的80%）收缩。在目标1中，我们将研究通过股外侧肌穿刺活检获得的单纤维，以比较年轻和老年久坐男性和女性，老年晚年锻炼者（最近10年的锻炼者）和老年终身锻炼组的单纤维功能，经济性和疲劳。我们的假设是，老年人的纤维功能主要是在动态收缩过程中受到峰值功率降低、张力发展速率降低和经济性降低的影响，而等长力保持良好。我们的初步数据还表明，老年人的肌纤维对低pH值和高无机磷酸盐的疲劳效应更敏感。我们预计快纤维比慢纤维更容易受到年龄的影响，并且功能损失是非锻炼者>晚年锻炼者>终身锻炼者。目的2将测试的假设，即年龄引起的变化，在动态运动过程中增加整个肌肉的外周疲劳，导致更大的肌肉疲劳与年轻人相比。我们将使用经颅磁刺激来评估整个肌肉的疲劳，并表明中枢疲劳并不随年龄的动态疲劳收缩而不同。在目标3中，我们将测试新运动训练的有效性，并假设它将改善全身任务，整体肌肉和单纤维性能（峰值功率和代谢）以及抗疲劳性。训练前后将进行肌肉活检、TMS和MRS。这些结果将提供重要的新信息，这些信息将转化为临床上重要的运动计划，以提高生活质量并降低衰老的医疗保健成本。

 DESCRIPTION (provided by applicant): The ability of older adults to perform routine daily activities is compromised by the loss of muscle mass (sarcopenia) and reduced power, and the problem is exacerbated by the development of muscle fatigue. This proposal will address these issues by studying fatigue induced by dynamic contractions in older men and women (= 70 years). We take a translational approach by examining the mechanisms of fatigue from dynamic contractions of single fibers (from muscle biopsies), whole muscle (magnetic resonance spectroscopy, MRS) and within the neuromuscular system (using transcranial magnetic stimulation, TMS). The hypothesis is that older adults fatigue more rapidly than young adults during dynamic contractions due to age-related inefficiencies inherent to skeletal muscle fiber (peripheral fatigue) rather than greater fatigue in the central nervous system (central fatigue). Our experimental design includes a comprehensive study of both men and women to examine sex differences. This is particularly important given the realization that fatigability in older women has received minimal attention despite the greater vulnerability to older women. A secondary goal is to test a novel exercise paradigm in protecting older adults from fatigue. The hypothesis is that training with slow six second shortening and six second lengthening contractions at velocities and forces known to elicit peak power will improve whole muscle and body performance, muscle fiber size and function in older adults to a greater extent than traditional high resistance (80% of one repletion maximum) contractions. In Aim 1, we will study single fibers obtained by needle biopsy from the vastus lateralis muscle to compare single fiber function, economy and fatigue in young and old sedentary men and women, and old late-life exercisers (exercisers for ~the last 10 years) and old life-long exercise groups. Our hypothesis is that fiber function in older adults is compromised mainly during dynamic contractions by a reduced peak power, rate of tension development, and economy, while isometric force is well maintained. Our preliminary data also suggests that muscle fibers from older adults are more sensitive to the fatiguing effects of low pH and high inorganic phosphate. We expect fast fibers to be more effected by age than slow fibers, and the functional loss to be non-exercisers>late-life exercisers>life-long exercisers. Aim 2 will test the hypothesis that age-induced change in peripheral fatigue of whole muscle is increased during dynamic exercise resulting in greater muscle fatigue compared with young adults. We will use TMS to assess fatigue in the whole muscle and to show that central fatigue does not differ with age for dyanmic fatiguing contractions. In Aim 3, we will test the effectiveness of the novel exercise training and the hypothesis that it will improve whole body tasks, whole muscle and single fiber performance (peak power and metabolism), and resistance to fatigue. Muscle biopsies, TMS and MRS will be performed before and after training. These outcomes will provide important new information that will translate into clinically important exercise programs to improve quality of life and reduce health care costs with aging.