Dillon E Lichar
Division of Endocrinology and Metabolism, Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
Amino Acids. 2013 Sep;45(3):431-41. doi: 10.1007/s00726-012-1438-0. Epub 2012 Dec 14.
Aging is associated with a gradual decline in skeletal muscle mass and strength leading to increased risk for functional impairments. Although basal rates of protein synthesis and degradation are largely unaffected with age, the sensitivity of older muscle cells to the anabolic actions of essential amino acids appears to decline. The major pathway through which essential amino acids induce anabolic responses involves the mammalian target of rapamycin (mTOR) Complex 1, a signaling pathway that is especially sensitive to regulation by the branched chain amino acid leucine. Recent evidence suggests that muscle of older individuals require increasing concentrations of leucine to maintain robust anabolic responses through the mTOR pathway. While the exact mechanisms for the age-related alterations in nutritional signaling through the mTOR pathway remain elusive, there is increasing evidence that decreased sensitivity to insulin action, reductions in endothelial function, and increased oxidative stress may be underlying factors in this decrease in anabolic sensitivity. Ensuring adequate nutrition, including sources of high quality protein, and promoting regular physical activity will remain among the frontline defenses against the onset of sarcopenia in older individuals.
衰老与骨骼肌质量和力量的逐渐下降有关，从而导致功能障碍风险增加。尽管蛋白质合成和降解的基础速率在很大程度上不受年龄影响，但老年肌肉细胞对必需氨基酸合成代谢作用的敏感性似乎有所下降。必需氨基酸诱导合成代谢反应的主要途径涉及雷帕霉素哺乳动物靶蛋白（mTOR）复合物1，这是一条对支链氨基酸亮氨酸的调节特别敏感的信号通路。最近的证据表明，老年人的肌肉需要越来越高浓度的亮氨酸，以通过mTOR途径维持强劲的合成代谢反应。虽然通过mTOR途径的营养信号传导中与年龄相关的变化的确切机制仍然难以捉摸，但越来越多的证据表明，对胰岛素作用的敏感性降低、内皮功能减退和氧化应激增加可能是合成代谢敏感性降低的潜在因素。确保充足的营养，包括优质蛋白质来源，并促进定期体育活动，仍将是预防老年人肌肉减少症发生的一线防御措施。
