Increasing muscle capillarization to enhance responses to strength training in sarcopenia

骨质疏松症，也就是与衰老相关的肌肉质量下降，影响着15%的70岁以上的人。 在这个年龄段之后，肌肉质量的额外损失可能达到每十年15%。石棺减少症的存在 与身体残疾、生活质量差、全因死亡率和直接医疗费用有关 相当于每年185亿美元。减少骨质疏松症的患病率和后果将导致 在健康和保健成本节约方面有很大的改善；然而，没有有效的 到目前为止，对石棺减少症和患有石棺减少症的老年人的治疗可能只有最小的肌肉反应 至单纯抗阻运动训练(RT)。因为骨质疏松症成人的骨骼肌较少 毛细血管和可能缺乏维持合成代谢潜能所需的充分灌流，我们建议 RT促进肌肉肥大的能力可能部分依赖于毛细血管的增加。这 初步研究将检验有氧运动训练增加骨骼肌毛细血管形成的假设 放疗前(AEX)治疗可改善肌纤维大小和质量对放疗的反应 成年人。这将通过两个目标来检验。目的1：确定为期3个月的有氧运动训练的效果 然后进行3个月的耐力训练(AEXRT)与3个月的单独耐力训练(RT)进行比较 骨骼肌形态(毛细血管形成和纤维大小)。目标2：确定 AEXRT与单独RT对骨质疏松症老年人骨骼肌质量和力量的影响比较。 我们将研究32名有骨钙素的老年人(70岁以上)，随机分为AEXRT组和单独RT组 (n=16/组)，性别和种族匹配。AEXRT组的参与者将接受3个月的AEX 训练以增加骨骼肌的毛细血管化，随后进行3个月的RT。RT组的参与者 将接受3个月的RT，没有预先干预以影响毛细血管形成。在之前和之后 干预措施，参与者将完成研究测试，包括：a)股外侧肌活组织检查 测量骨骼肌纤维大小和毛细血管形成；b)肌肉力量和力量测试(Biodex) 确定肌肉功能；以及c)DXA和CT扫描以确定肌肉质量、体积和质量。我们会 还要测量步态速度、握力和6分钟步行距离，并评估身体和机动性 使用修改后的物理性能测试功能。重复测量将使用方差分析来确定 AEXRT与单纯RT疗效比较。这项以患者为中心的研究将是第一个测试简单的 和实用的血管干预(增加骨骼肌毛细血管化)，以改善对RT的反应 骨质疏松症老年人。虽然这些发现可以立即转化为更理想的运动 针对老年人的计划，在细胞、组织、区域、全身和 功能水平将为更大规模的试验提供证据，以建立锻炼、营养、 药物或补充疗法，以改善骨质疏松症。

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.