Increasing muscle capillarization to enhance responses to strength training in sarcopenia

肌肉减少症，或与年龄相关的肌肉质量损失，影响>15%的70岁以上的个体， 在这个年龄之后，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、全因死亡率和直接卫生保健费用有关 每年达到185亿美元。减少肌肉减少症的患病率和后果将导致 保健和保健费用节省方面的实质性改善;然而， 到目前为止，对肌肉减少症的治疗和患有肌肉减少症的老年人可能只有最小的肌肉反应 抗阻训练（RT）。因为肌肉减少症的成年人的骨骼肌 毛细血管化，可能缺乏足够的灌注需要维持合成代谢的潜力，我们建议， RT促进肌肉肥大的能力可能部分依赖于毛细作用的增加。这 一项初步研究将检验有氧运动训练增加骨骼肌毛细血管化的假设 (AEX)将导致肌肉减少老年人的肌纤维大小和质量对RT的反应改善 成年人了这将通过两个目标来检验。目的1：确定3个月有氧运动训练的效果 随后进行3个月的阻力训练（AEX阻力训练），与3个月的单独阻力训练（RT）相比， 骨骼肌形态学（毛细血管化和纤维大小）。目标2：确定 AEX骨水泥RT与RT单独治疗相比对肌肉减少老年人骨骼肌质量和力量的影响。 我们将研究32名肌肉减少的老年人（70岁以上），随机接受AEX双抗RT或单独RT治疗。 （n=16/组），性别和人种匹配。AEX ATERT组的参与者将接受3个月的AEX 训练以增加骨骼肌毛细血管化，随后进行3个月的RT。RT组的参与者 将接受3个月的RT，之前未进行干预以影响毛细血管化。之前和之后 参与者将完成研究测试，包括：a）股外侧肌活检， 测量骨骼肌纤维尺寸和毛细作用; B）肌肉强度和力量测试（Biodex）， c）DXA和CT扫描以确定肌肉质量、体积和质量。我们将 还测量步态速度、握力和6分钟步行距离，并评估身体和活动能力 使用修改的物理性能测试功能。将使用重复测量ANOVA确定 AEX双RT与单纯RT的效果比较。这项以病人为导向的研究将是第一个测试一个简单的 和实际的血管干预（增加骨骼肌毛细血管化），以改善对RT的反应， 肌肉萎缩的老年人虽然这些发现可以立即转化为更优化的运动 老年人的计划，在细胞，组织，区域，全身， 功能水平将为更大规模的试验提供证据，以建立运动，营养， 药物或补充疗法以改善肌肉减少症。

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.