Immune Function and Muscle Adaptations to Resistance Exercise in Older Adults

老年人的免疫功能和肌肉对抗阻运动的适应

• 批准号: 9178595
• 负责人: RICHARD A. DENNIS
• 金额: --
• 依托单位: CENTRAL ARKANSAS VETERANS HLTHCARE SYS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178595
• 关键词: 1-Phosphatidylinositol 3-Kinase; Acute; Affect; Age; Aging; Anti-Inflammatory Agents; Anti-inflammatory; Antibody Response; Area; Arginine; Biopsy; Blood; Body measure procedure; Cell Proliferation; Cell physiology; Cells; Chronic Disease; Clinical; Complement; Consumption; Dietary Intervention; Diphtheria; Diphtheria Toxoid; Double-Blind Method; Elderly; Equilibrium; Exercise; Fiber; Functional disorder; Gait; Glutamine; Growth; Growth Factor; Health; Immune; Immune Targeting; Immune response; Immune system; Individual; Inflammation; Inflammatory; Investigation; Lead; Maintenance; Measures; Methods; Modeling; Monitor; Mononuclear; Muscle; Muscle Fibers; Muscle function; Muscular Atrophy; Musculoskeletal System; Nuclear; Outcome; Participant; Pertussis Vaccine; Phase; Phenotype; Placebos; Production; Quality of life; Randomized; Regulation; Rehabilitation therapy; Research; Role; Signal Pathway; Signal Transduction; Skeletal Muscle; Stimulus; Supplementation; System; T-Lymphocyte; Testing; Tetanus; Tetanus Vaccine; Training; Training Programs; Training Support; Vaccinated; Vaccination; Variant; Veterans; X-Ray Computed Tomography; age effect; age related; base; clinically relevant; cytokine; dietary supplements; exercise training; follow-up; immune function; immune system function; immunological status; improved; innate immune function; macrophage; muscle form; muscle strength; nutritional supplementation; public health relevance; randomized placebo controlled trial; randomized trial; resistance exercise; response; sarcopenia; satellite cell; strength training; vastus lateralis

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.

描述（由申请人提供）： 目的：该研究将检查免疫功能在老年人中通过抵抗训练改善肌肉质量，力量和功能的影响。还将检查在长期随访期间对这些福利的维护。该目标将通过营养补充剂（肌肉装甲）的双盲随机安慰剂对照试验来实现，证据表明可以改善免疫功能，促进肌肉生长和抵消肌肉损失。研究前提是，衰老会导致免疫系统对运动等刺激的反应能力降低。该研究建议，补充剂将通过促进老年人的免疫功能从促炎性状态转向支持肌肉生长和维持的状态来改善肌肉健康。研究计划：该研究将随机将退伍军人（60-80岁，n = 40岁）随机参与三期研究中的补充或安慰剂组。参与的阶段对应于三个特定目标。 AIM 1将确定补充2周是否改善免疫功能。体液免疫功能将被评估为对疫苗接种的反应。先天免疫功能将被测量为我们以前的研究表明受衰老影响的全身性和细胞对急性耐药性运动的反应。 AIM 2将确定在渐进的高强度耐药性训练12周期间补充是否会提高肌肉大小（CT扫描），强度和功能（步态和平衡）的改善。还将测量细胞水平的肌肉适应。 AIM 3将确定锻炼训练后是否继续为26周补充，可以促进肌肉大小，力量和功能的增益的保留。然后，将使用多变量测试来比较目标1、2和3之间的结果，以确定免疫功能是否与肌肉适应训练或逐渐减弱相关。方法：在研究过程中，参与者将接受7次血液抽血和五个股外侧的肌肉活检，以便可以测量补充剂对免疫功能和细胞适应训练的影响。其中三种血液将用于评估对破伤风，百日咳和白喉疫苗的抗体反应。在接受训练之前和之后进行了两周的补充之前和之后，将在训练前后进行肌肉和血液。免疫功能将使用基于促炎和抗炎细胞因子水平，特定T细胞亚群的平衡以及单核细胞的增殖能力来测量免疫功能。免疫功能将根据特定细胞因子和生长因子的巨噬细胞含量在肌肉中进行测量。我们先前的研究表明，这些肌肉度量与训练后的大小和强度增强密切相关。还将测量包括核因子-K B和PI3激酶在内的关键信号通路。将收集第五个活检 根据卫星细胞的数量以及肌核和纤维大小的变化，训练后训练以测量细胞水平的适应性。与这些措施相关的假设将用80％的功率测试，以检测补充剂组和安慰剂组之间的平均值至少0.8标准偏差差异。临床相关性：运动显然能够影响免疫功能。但是，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。该研究还将检查训练研究的损失，这是老年人的重要问题。因此，这项研究将有潜在地了解我们对老年人肌肉增益和损失机制的理解，但更重要的是，该研究将评估营养干预措施，以作为在衰老期间支持锻炼肌肉健康的补充。针对免疫系统可能是老兵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。