Sakuma Kunihiro, Aoi Wataru, Yamaguchi Akihiko
Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto, 606-8522, Japan.
Pflugers Arch. 2017 Jun;469(5-6):573-591. doi: 10.1007/s00424-016-1933-3. Epub 2017 Jan 19.
Skeletal muscle provides a fundamental basis for human function, enabling locomotion and respiration. Muscle loss occurs as a consequence of several chronic diseases (cachexia) and normal aging (sarcopenia). Although many negative regulators (atrogin-1, muscle ring finger-1, nuclear factor-kappaB (NF-κB), myostatin, etc.) have been proposed to enhance protein degradation during both sarcopenia and cachexia, the adaptation of these mediators markedly differs within both conditions. Sarcopenia and cachectic muscles have been demonstrated to be abundant in myostatin-linked molecules. The ubiquitin-proteasome system (UPS) is activated during rapid atrophy model (cancer cachexia), but few mediators of the UPS change during sarcopenia. NF-κB signaling is activated in cachectic, but not in sarcopenic, muscle. Recent studies have indicated the age-related defect of autophagy signaling in skeletal muscle, whereas autophagic activation occurs in cachectic muscle. This review provides recent research advances dealing with molecular mediators modulating muscle mass in both sarcopenia and cachexia.
骨骼肌为人体功能提供了基本基础，使运动和呼吸成为可能。肌肉流失是多种慢性疾病（恶病质）和正常衰老（肌肉减少症）的结果。尽管已经提出了许多负调节因子（萎缩基因1、肌肉环形指蛋白1、核因子κB（NF-κB）、肌肉生长抑制素等）来增强肌肉减少症和恶病质期间的蛋白质降解，但这些介质在两种情况下的适应性明显不同。肌肉减少症和恶病质肌肉中已被证明富含与肌肉生长抑制素相关的分子。泛素-蛋白酶体系统（UPS）在快速萎缩模型（癌症恶病质）中被激活，但在肌肉减少症期间很少有UPS的介质发生变化。NF-κB信号在恶病质肌肉中被激活，但在肌肉减少症肌肉中未被激活。最近的研究表明骨骼肌中存在与年龄相关的自噬信号缺陷，而自噬激活发生在恶病质肌肉中。本综述提供了有关调节肌肉减少症和恶病质中肌肉质量的分子介质的最新研究进展。
