Increasing muscle capillarization to enhance responses to strength training in sarcopenia

增加肌肉毛细血管化以增强肌少症患者对力量训练的反应

基本信息

批准号：
9993190
负责人：
Steven J Prior
金额：
$ 20.69万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9993190
关键词：
Address Adult Aerobic Exercise Affect Age Age-Years Aging Analysis of Variance Area Biopsy Blood Vessels Blood capillaries Complementary therapies Cost Savings Cross-Sectional Studies Development Disease Dual-Energy X-Ray Absorptiometry Elderly Exercise Fiber Foundations Gait speed Health Health Care Costs Human Hypertrophy Impairment Individual Intervention Link Literature Measures Mediating Morphology Muscle Muscle Fibers Muscle function Muscular Atrophy Nutritional Outcome Study Participant Perfusion Pharmacologic Substance Phenotype Physical Function Physical Performance Physical activity Pilot Projects Prevalence Publishing Quality of life Race Randomized Reporting Research Skeletal Muscle Study Subject Testing Thigh structure Tissues Training Translating United States National Institutes of Health Walking Woman X-Ray Computed Tomography age related angiogenesis base care costs clinical practice clinically relevant density design effective therapy exercise program exercise training functional outcomes improved indexing intervention effect intervention participants men mortality muscle form muscle hypertrophy muscle strength older men older women patient oriented research performance tests physically handicapped primary outcome resistance exercise response sarcopenia secondary outcome sex skeletal strength training therapeutic target vastus lateralis

项目摘要

Sarcopenia, or the aging-related loss of muscle mass, affects >15% of individuals over 70 years of age, and the additional loss of muscle mass after this age can reach 15% per decade. The presence of sarcopenia is associated with physical disability, poor quality of life, all-cause mortality, and direct health care costs amounting to $18.5 billion per year. Reducing the prevalence and consequences of sarcopenia would result in substantial improvements in health as well as heath care cost savings; however, there has been no effective treatment for sarcopenia to date and older adults with sarcopenia may have only minimal muscular responses to resistance exercise training (RT) alone. Because sarcopenic adults have low muscle skeletal muscle capillarization and may lack the adequate perfusion needed to maintain anabolic potential, we propose that the ability of RT to promote muscle hypertrophy may, in part, be dependent on increases in capillarization. This pilot study will test the hypothesis that increasing skeletal muscle capillarization with aerobic exercise training (AEX) prior to RT will result in an improved response of muscle fiber size and mass to RT in sarcopenic older adults. This will be tested through two aims. Aim 1: Determine the effects of 3-month aerobic exercise training followed by 3-month resistance training (AEXRT) compared with 3-month resistance training alone (RT) on skeletal muscle morphology (capillarization and fiber size) in sarcopenic older adults. Aim 2: Determine the effects of AEXRT compared with RT alone on skeletal muscle mass and power in sarcopenic older adults. We will study 32 sarcopenic older adults (70+ years of age) randomized to either AEXRT or RT alone (n=16/group) with matching for sex and race. Participants in the AEXRT group will undergo 3 months of AEX training to increase skeletal muscle capillarization, followed by 3 months of RT. Participants in the RT group will undergo 3 months of RT with no preceding intervention to affect capillarization. Before and after the interventions, participants will complete research testing consisting of: a) vastus lateralis muscle biopsies to measure skeletal muscle fiber size and capillarization; b) muscle strength and power testing (Biodex) to determine muscle function; and c) DXA and CT scans to determine muscle mass, volume and quality. We will also measure gait speed, handgrip strength and 6-minute walk distance and assess physical and mobility function using the Modified Physical Performance Test. Repeated measures ANOVA will be used determine the effects of AEXRT compared with RT only. This patient-oriented study would be the first to test a simple and practical vascular intervention (increasing skeletal muscle capillarization) to improve responses to RT in sarcopenic older adults. While these findings could immediately be translated into more optimal exercise programs for older adults, comprehensive phenotyping at the cellular, tissue, regional, whole-body, and functional levels will provide evidence for a larger trial to establish vascular targets for exercise, nutritional, pharmaceutical or complementary therapies to ameliorate sarcopenia.

肌肉减少症或肌肉质量与衰老相关的损失，> 70岁以上的个体> 15％而且，该年龄后的肌肉质量的额外损失可以达到每十年15％。肌肉减少症的存在与身体残疾，生活质量差，全因死亡率和直接医疗保健费用有关每年总计185亿美元。减少肌肉减少症的患病率和后果将导致健康和卫生护理成本节省的大幅改善；但是，没有有效迄今为止的肌肉减少症和肌肉减少症的老年人的治疗可能只有最小的肌肉反应仅靠抵抗运动训练（RT）。因为肌肉减少成年人的肌肉骨骼肌较低毛细管化，可能缺乏保持合成代谢潜力所需的足够的灌注，我们建议 RT促进肌肉肥大的能力可能部分取决于毛细血管化的增加。这试点研究将检验以下假设，即有氧运动训练增加骨骼肌毛细血管（AEX）在RT之前，肌肉纤维尺寸和质量对肌肉减少型的肌肉大小和质量的响应得到改善成年人。这将通过两个目标进行测试。目标1：确定3个月有氧运动训练的影响与仅3个月的阻力训练（RT）相比肌肉减少型老年人的骨骼肌形态（毛细血管和纤维大小）。目标2：确定与单独的RT相比，AEXRT的影响对肌肉减少型老年人的骨骼肌质量和功率。我们将研究32名肌肉减少型老年人（70岁以上）单独将AEX或RT随机分配（n = 16/组）与性别和种族相匹配。 AEXRT组的参与者将经历3个月的AEX 训练以增加骨骼肌毛细管化，然后进行3个月的RT。 RT组的参与者将经历3个月的RT，没有前面的干预措施以影响毛细管化。之前和之后干预措施，参与者将完成包括：a）巨大外侧肌肉活检的研究测试测量骨骼肌纤维的大小和毛细管； b）肌肉力量和功率测试（Biodex）确定肌肉功能； c）DXA和CT扫描以确定肌肉质量，体积和质量。我们将还可以测量获得速度，手工束强度和步行6分钟的距离，并评估身体和机动性使用修改的身体绩效测试功能。重复测量方差分析将确定 AEXRT的效果与RT相比。这项面向患者的研究将是第一个测试简单的研究和实际的血管干预（增加骨骼肌毛细管化），以改善对RT的反应肌肉减少型老年人。虽然这些发现可以立即转化为最佳练习针对老年人的计划，在细胞，组织，区域，全身和功能水平将为更大的试验提供证据，以建立运动，营养，，改善肌肉减少症的药物或完整疗法。