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亮氨酸经LAT1介导调控衰老骨骼肌蛋白质合成的机制研究进展

柯余^1,2, 戴志强³, 阳颖^1,2, 吴慧雯^1,2, 赵艳^1,2, 尚画雨⁴, 夏志^1,2,*

¹温州大学体育与健康学院，温州 325035；²温州市生物健康材料与化学重点实验室，温州 325035；³南昌大学体育学院，南昌 330031；⁴成都体育学院运动医学与健康学院，成都 610041

摘要

衰老性骨骼肌萎缩是指因衰老导致骨骼肌质量流失及功能减退的增龄性机能退化症，而骨骼肌对亮氨酸等营养物质合成代谢刺激的反应削弱(合成代谢抵抗)则是其发生与发展的重要诱因。近年来有研究提示，大分子中性氨基酸转运载体1(large neutral amino acid-transpoter 1, LAT1/SLC7A5)可能在增强亮氨酸感应过程中发挥重要作用，从而调节衰老骨骼肌蛋白质合成。本文通过对LAT1 的结构、功能以及其调节衰老骨骼肌蛋白质合成的关键分子进行综述，分析其作为亮氨酸跨膜转运蛋白与衰老骨骼肌蛋白质合成之间的潜在关联，以期探寻衰老性骨骼肌萎缩的新机制与防治新思路，并为相关靶点在临床转化医学领域的应用提供依据。

关键词： 衰老性骨骼肌萎缩; 合成代谢抵抗; 亮氨酸; 大分子中性氨基酸转运载体1; 骨骼肌蛋白质合成

Research progress on the mechanism of leucine regulation of protein synthesis in aging skeletal muscle through LAT1

KE Yu^1,2, DAI Zhi-Qiang³, YANG Ying^1,2, WU Hui-Wen^1,2, ZHAO Yan^1,2, SHANG Hua-Yu⁴, XIA Zhi^1,2,*

¹ College of Physical Education and Health, Wenzhou University, Wenzhou 325035, China；²Key Lab of Biohealth Materials and Chemistry of Wenzhou, Wenzhou 325035, China；³School of Physical Education, Nanchang University, Nanchang 330031, China；⁴School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China

Abstract

Age-related sarcopenia is a degenerative disease characterized by the decline in skeletal muscle mass and function during the aging process. Anabolic resistance, which refers to the diminished response of skeletal muscle to anabolic stimulation from leucine and other nutrients, is a significant contributing factor to its development. Recent studies have suggested that large neutral amino acid-transporter 1 (LAT1/SLC7A5) may play an important role in enhancing leucine's effects on protein synthesis in aging skeletal muscle. In this paper, the structure and function of LAT1 and its key molecules regulating aging skeletal muscle protein synthesis were reviewed, and the potential relationship between LAT1, as a transmembrane transporter of leucine, and protein synthesis in aging skeletal muscle was analyzed. The aim is to explore new mechanisms and insights for prevention and treatment of age-related sarcopenia, and provide reference for the application of relevant targets in clinical translational medicine.

Key words: age-related sarcopenia; anabolic resistance; leucine; large neutral amino acid-transporter 1; skeletal muscle protein synthesis

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通讯作者：夏志　　E-mail:

引用本文：

柯余, 戴志强, 阳颖, 吴慧雯, 赵艳, 尚画雨, 夏志. 亮氨酸经LAT1介导调控衰老骨骼肌蛋白质合成的机制研究进展[J]. 生理学报 2024; 76 (6): 1001-1018.

KE Yu, DAI Zhi-Qiang, YANG Ying, WU Hui-Wen, ZHAO Yan, SHANG Hua-Yu, XIA Zhi. Research progress on the mechanism of leucine regulation of protein synthesis in aging skeletal muscle through LAT1. Acta Physiol Sin 2024; 76 (6): 1001-1018 (in Chinese with English abstract).