Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults

描述(由申请人提供)： 目的：研究阻力训练对老年人免疫功能改善肌肉质量、力量和功能的影响。还将审查在长期后续行动期间维持这些福利的情况。这一目标将通过一种营养补充剂(肌肉盔甲)的双盲随机安慰剂对照试验来实现，证据表明，这种营养补充剂可以改善免疫功能，促进肌肉生长，并抵消肌肉损失。研究的前提是，衰老会导致免疫系统对运动等刺激的反应能力下降。研究表明，补充剂将通过促进老年人的免疫功能从促炎状态转变为支持肌肉生长和维护的状态来改善肌肉健康。研究计划：该研究将随机选择退伍军人(60-80岁，N=40)参加补充剂组或安慰剂组，进行三个阶段的研究。参与的阶段与三个具体目标相对应。目标1将确定两周的补充剂是否能改善免疫功能。体液免疫功能将作为对疫苗接种的反应进行评估。先天免疫功能将通过系统和细胞对急性阻力运动的反应来衡量，我们之前的研究表明，这一反应受到年龄的影响。目标2将确定在12周的递进性高强度耐力训练中补充是否能促进肌肉大小(CT扫描)、力量和功能(步态和平衡)的改善。还将测量细胞水平上的肌肉适应能力。目标3将确定在运动训练完成后继续补充26周是否有助于保持肌肉大小、力量和功能的增长。然后将使用多变量测试来比较目标1、目标2和目标3之间的结果，以确定免疫功能是否与肌肉对训练或非训练的适应相关。方法：在研究过程中，参与者将接受7次股外侧肌抽血和5次肌肉活组织检查，以衡量补充剂对免疫功能和细胞对训练的适应性的影响。其中三次抽血将用于评估破伤风、百日咳和白喉疫苗的抗体反应。肌肉和血液将在训练前和训练前两周的补充前和训练后的一轮运动之前和之后进行采集。免疫功能将使用基于促炎和抗炎细胞因子水平、特定T细胞亚群之间的平衡以及单核细胞增殖能力的血液来测量。将根据巨噬细胞中特定细胞因子和生长因子的含量来测量肌肉的免疫功能。我们之前的研究表明，这些肌肉测量与训练后的体型和力量增长密切相关。包括核因子-kB和PI3激酶在内的关键信号通路也将被检测。将收集第五次活组织检查 训练后，根据卫星细胞和肌核数量以及纤维大小的变化，在细胞水平上衡量适应性。与这些措施相关的假设将以80%的能力进行测试，以检测补充剂组和安慰剂组之间至少0.8标准差的均值差异。临床意义：运动显然能够影响免疫功能。然而，这项拟议的研究将试图调节免疫功能，并确定对运动结果的影响。这项研究还将审查解除训练，这是老年人的一个重要问题，通常在训练研究中被省略。因此，这项研究可能会促进我们对老年人肌肉增减机制的理解，但更重要的是，该研究将评估营养干预作为锻炼的补充，以支持衰老期间的肌肉健康。针对免疫系统可能是老年退伍军人成功维持或恢复个人独立所必需的肌肉质量、力量和功能所需的优势。

DESCRIPTION (provided by applicant): Objective: The study will examine the influence of immune function in older adults on improvement of muscle mass, strength, and function by resistance training. The maintenance of those benefits during long- term follow-up will also be examined. This objective will be accomplished by a double-blind randomized placebo-controlled trial of a nutritional supplement (Muscle Armor) which evidence suggests can improve immune function, promote muscle growth, and counteract muscle loss. The study premise is that aging results in decreased ability of the immune system to respond to stimuli such as exercise. The study proposes that the supplement will improve muscle health by promoting a shift in immune function of older adults from a pro-inflammatory state towards a state which supports muscle growth and maintenance. Research Plan: The study will randomize veterans (age 60-80, N=40) to participate in the supplement or placebo groups in a three phase study. The phases of participation correspond to the three specific aims. Aim 1 will determine if 2-weeks of supplementation improves immune function. Humoral immune function will be assessed as the response to vaccination. Innate immune function will be measured as systemic and cellular responses to acute resistance exercise that our previous studies indicate are affected by aging. Aim 2 will determine if supplementation during 12-weeks of progressive high-intensity resistance training boosts improvement in muscle size (CT scan), strength, and function (gait and balance). Muscle adaptations at the cellular levels will also be measured. Aim 3 will determine if continued supplementation for 26-weeks after completion of exercise training promotes the retention of the gains in muscle size, strength, and function. Multivariable testing will then be used to compare the results between Aims 1, 2, and 3 to determine whether or not immune function is correlated with muscle adaptation to training or detraining. Methods: Participants will undergo seven blood draws and five muscle biopsies of the vastus lateralis over the course of the study so that the effects of the supplement on immune function and cellular adaptations to training can be measured. Three of the blood draws will be used to assess the antibody response to the tetanus, pertussis, and diphtheria vaccine. Muscle and blood will be collected before and after a bout of exercise conducted before and after the 2-weeks of supplementation prior to training. Immune function will be measured using the blood based on pro- and anti-inflammatory cytokine levels, the balance between specific T-cell subpopulations, and the proliferative capacity of mononuclear cells. Immune function will be measured in muscle based on macrophage content of specific cytokines and growth factors. Our previous study showed that these muscle measures strongly correlate with size and strength gain after training. Key signaling pathways including nuclear factor-k B and PI3 kinase will also be measured. A fifth biopsy will be collected post-training to measure adaptation at the cellular level based on changes in number of satellite cells and myonuclei and fiber size. Hypotheses related to these measures will be tested with 80% power to detect at least 0.8 standard deviations difference in means between the supplement and placebo groups. Clinical Relevance: Exercise is clearly able to affect immune function. However, the proposed study will attempt to modulate immune function and determine the effects on exercise outcomes. The study will also examine detraining, an important issue for older adults, that is usually omitted from training studies. Thus, the study will potentially advane our understanding of the mechanisms of muscle gain and loss in older adults, but more importantly, the study will evaluate a nutritional intervention as a complement to exercise for supporting muscle health during aging. Targeting the immune system may be the advantage needed for an older Veteran to successfully maintain or restore the muscle mass, strength, and function that is necessary for personal independence.