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

描述（由申请人提供）：肌肉减少症，即肌肉质量和力量随着年龄的增长而下降，是多因素造成的，部分原因是骨骼肌对膳食蛋白质的反应降低以及促炎细胞因子增加。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 细胞信号传导途径急剧刺激蛋白质合成，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来增加肌肉的氨基酸利用率。精氨酸还刺激其他合成代谢激素的分泌，并充当蛋白质合成的前体。膳食补充剂 Juven（Ross Laboratories）由 β-羟基-β-甲基丁酸 (HMB) 组成，它是亮氨酸、谷氨酰胺和精氨酸的活性代谢物。 Juven 是否可以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、安慰剂对照干预措施的具体目的是检验以下假设：在老年人中，Juven 与安慰剂相比，长期维持或增加四肢骨骼肌质量、肌肉体积和身体功能； 2）积极影响生活质量； 3) 降低炎症的血清生物标志物。年龄 > 64 岁的社区居住男性和女性将被随机分配每天接受两剂 Juven（3 g HMB、14g Gin、14g Arg）或等氮安慰剂（丙氨酸、谷氨酸、甘氨酸、丝氨酸），持续 6 个月。在基线、3 个月和 6 个月时，测量将包括 1) 通过黄金标准四室模型进行综合身体成分评估； 2)双能X线骨密度测定阑尾骨骼质量； 3) 磁共振成像骨骼肌体积； 4）身体机能通过tDattery的身体机能测试； 5) 通过经过验证的问卷和 SEIQoL-DW 来衡量生活质量，SEIQoL-DW 是一种评估工具，允许个人为自己定义“生活质量”的领域。 公共卫生相关性：该干预措施将生理结果（肌肉质量、肌肉体积、促炎生物标志物）与心理结果（生活质量）和实际身体功能测量全面联系起来。没有有效的方法来预防或逆转肌肉减少症。随着美国人口老龄化，实用、有效的干预措施至关重要。这项临床研究将为膳食补充剂提供证据基础，该补充剂显示出增强老年人肌肉代谢的潜力。

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.