Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0460, USA.
FASEB J. 2010 Oct;24(10):4117-27. doi: 10.1096/fj.09-150177. Epub 2010 Jun 14.
Age-related skeletal muscle loss is thought to stem from suboptimal nutrition and resistance to anabolic stimuli. Impaired microcirculatory (nutritive) blood flow may contribute to anabolic resistance by reducing delivery of amino acids to skeletal muscle. In this study, we employed contrast-enhanced ultrasound, microdialysis sampling of skeletal muscle interstitium, and stable isotope methodology, to assess hemodynamic and metabolic responses of older individuals to endurance type (walking) exercise during controlled amino acid provision. We hypothesized that older individuals would exhibit reduced microcirculatory blood flow, interstitial amino acid concentrations, and amino acid transport when compared with younger controls. We report for the first time that aging induces anabolic resistance following endurance exercise, manifested as reduced (by ∼40%) efficiency of muscle protein synthesis. Despite lower (by ∼40-45%) microcirculatory flow in the older than in the younger participants, circulating and interstitial amino acid concentrations and phenylalanine transport into skeletal muscle were all equal or higher in older individuals than in the young, comprehensively refuting our hypothesis that amino acid availability limits postexercise anabolism in older individuals. Our data point to alternative mediators of age-related anabolic resistance and importantly suggest correction of these impairments may reduce requirements for, and increase the efficacy of, dietary protein in older individuals.
与年龄相关的骨骼肌丢失被认为源于营养不足和对合成代谢刺激的抵抗。受损的微循环(营养)血流可能通过减少氨基酸向骨骼肌的输送,导致合成代谢抵抗。在这项研究中,我们采用对比增强超声、骨骼肌间质微透析采样和稳定同位素方法,评估了在控制氨基酸供应的情况下,老年人对耐力型(步行)运动的血液动力学和代谢反应。我们假设与年轻对照组相比,老年人在运动后会表现出微循环血流量、间质氨基酸浓度和氨基酸转运减少。我们首次报道,衰老会导致耐力运动后的合成代谢抵抗,表现为肌肉蛋白质合成效率降低(约 40%)。尽管老年人的微循环流量比年轻人低(约 40-45%),但循环和间质氨基酸浓度以及苯丙氨酸向骨骼肌的转运在老年人中均高于年轻人,这全面反驳了我们的假设,即氨基酸供应限制了老年人运动后的合成代谢。我们的数据指向与年龄相关的合成代谢抵抗的其他介质,并且重要的是,表明纠正这些损伤可能会减少老年人对膳食蛋白质的需求,并提高其有效性。