Dietary supplements and aging muscle: specific amino acids to combat sarcopenia

描述（由申请人提供）：骨骼肌减少症，肌肉质量和力量随着年龄的增长而下降，是多因素的，部分原因是骨骼肌对膳食蛋白质的反应下降以及促炎细胞因子的增加。口服特定氨基酸有望抵消老年人的肌肉损失。具体来说，亮氨酸通过mTOR细胞信号通路强烈刺激蛋白质合成，而谷氨酰胺（Gin），其他氨基酸和谷胱甘肽的前体，可能会减少炎症。精氨酸（Arg）可以进一步调节炎症，调节mTOR通路，并通过刺激胰岛素分泌和血管舒张增加氨基酸对肌肉的可用性。精氨酸还刺激其他合成代谢激素的分泌，并作为蛋白质合成的前体。膳食补充剂Juven（罗斯实验室）由β -羟基- β -甲基丁酸盐（HMB）组成，它是亮氨酸、谷氨酰胺和精氨酸的活性代谢物。Juven是否能改善老年人的肌肉质量、质量和功能尚不清楚。这项随机、双盲、安慰剂对照干预的具体目的是检验假设：在老年人中，Juven与安慰剂相比，长期维持或增加了阑尾骨骼肌质量、肌肉体积和身体功能；2)积极影响生活质量；3)降低血清炎症生物标志物。居住在社区的年龄在0 - 64岁的男性和女性将随机接受两剂Juven （3g HMB, 14g Gin, 14g Arg）或一种等氮安慰剂（丙氨酸，谷氨酸，甘氨酸，丝氨酸），每天6个月。在基线、3个月和6个月时，测量将包括1)通过金标准四室模型进行全面的身体成分评估；2)双能x线骨量仪测定阑尾骨量；3)磁共振成像骨骼肌体积；4)物理功能通过一个电池的物理性能测试；5)通过有效的问卷和SEIQoL-DW（一种允许个人为自己定义“生活质量”领域的评估工具）来评估生活质量。

DESCRIPTION (provided by applicant): Sarcopenia, the decline in muscle mass and strength with aging, is multifactorial, due partly to the decreased response of skeletal muscle to dietary protein as well as increased pro-inflammatory cytokines. Oral intake of particular amino acids shows promise to counteract muscle loss in older adults. Specifically, leucine acutely stimulates protein synthesis via mTOR cell signaling pathways, whereas glutamine (Gin), a precursor to other amino acids and glutathione, may decrease inflammation. Arginine (Arg) may further modulate inflammation, regulate mTOR pathways, and increase availability of amino acids to muscle by stimulating insulin secretion and vasodilation. Argine also stimulates secretion of other anabolic hormones and acts as a precursor for protein synthesis. The dietary supplement Juven (Ross Laboratories) is comprised of beta-hydroxy-beta-methylbutyrate (HMB), an active metabolite of leucine, glutamine, and arginine. Whether Juven can improve muscle mass, quality, and function in older adults is unknown. The Specific Aims of this randomized, double-blind, placebo-controlled intervention are to test the hypotheses that, among older adults, Juven versus placebo chronically 1) results in maintenance or gains in appendicular skeletal muscle mass, muscle volume, and physical function; 2) positively affects quality of life; and 3) decreases serum biomarkers of inflammation. Community-dwelling men and women, ages >64 years will be randomized to receive either two doses of Juven (3 g HMB, 14g Gin, 14g Arg) or an isonitrogenous placebo (alanine, glutamic acid, glycine, serine) daily for 6 months. At baseline, 3 months, and 6 months, measurements will include 1) comprehensive body composition evaluation by the gold-standard four-compartment model; 2)appendicular skeletal mass by dual energy X-ray absorptiometry; 3) skeletal muscle volume by magnetic resonance imaging; 4) physical function by a tDattery of physical performance tests; and 5) quality of life by validated questionnaire and the SEIQoL-DW, an assessment tool that allows individuals to define domains of "quality of life" for themselves. PUBLIC HEALTH RELEVANCE: This intervention holistically links physiological outcomes (muscle mass, muscle volume, pro- inflammatory biomarkers) to psychological outcomes (quality of life) and practical physical function measures. No effective means exist to prevent or reverse sarcopenia. As the American population ages, practical, effective interventions will be critical. This clinical research will contribute to an evidence base for dietary supplements that shows potential to enhance muscle metabolism in older adults.