Sakuma Kunihiro, Aoi Wataru, Yamaguchi Akihiko
Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, 1-1 Hibarigaoka, Tenpaku-cho, Toyohashi, 441-8580, Japan,
Pflugers Arch. 2015 Feb;467(2):213-29. doi: 10.1007/s00424-014-1527-x. Epub 2014 May 7.
The world's elderly population is expanding rapidly, and we are now faced with the significant challenge of maintaining or improving physical activity, independence, and quality of life in the elderly. Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Muscle loss has been linked with several proteolytic systems, including the ubuiquitin-proteasome, lysosome-autophagy, and tumor necrosis factor (TNF)-α/nuclear factor-kappaB (NF-κB) systems. Although many factors are considered to regulate age-dependent muscle loss, this gentle atrophy is not affected by factors known to enhance rapid atrophy (denervation, hindlimb suspension, etc.). In addition, defects in Akt-mammalian target of rapamycin (mTOR) and serum response factor (SRF)-dependent signaling have been found in sarcopenic muscle. Intriguingly, more recent studies indicated an apparent functional defect in autophagy- and myostatin-dependent signaling in sarcopenic muscle. In this review, we summarize the current understanding of the adaptation of many regulators in sarcopenia.
全球老年人口正在迅速增长，我们现在面临着一项重大挑战，即维持或改善老年人的身体活动、独立性和生活质量。肌肉减少症是与年龄相关的骨骼肌质量流失，其特征是肌肉数量和质量下降，导致运动逐渐减慢、力量和功率下降、跌倒相关损伤风险增加，并且常常伴有身体虚弱。由于肌肉减少症很大程度上归因于影响纤维大小、线粒体稳态和细胞凋亡的各种分子介质，这些有害变化的机制为药物研发提供了众多治疗靶点。肌肉流失与多种蛋白水解系统有关，包括泛素-蛋白酶体系统、溶酶体-自噬系统和肿瘤坏死因子（TNF）-α/核因子-κB（NF-κB）系统。尽管许多因素被认为可调节年龄依赖性肌肉流失，但这种轻度萎缩不受已知会加剧快速萎缩的因素（去神经支配、后肢悬吊等）影响。此外，在肌肉减少症患者的肌肉中发现了Akt-雷帕霉素哺乳动物靶蛋白（mTOR）和血清反应因子（SRF）依赖性信号通路的缺陷。有趣的是，最近的研究表明，在肌肉减少症患者的肌肉中，自噬和肌肉生长抑制素依赖性信号通路存在明显的功能缺陷。在这篇综述中，我们总结了目前对肌肉减少症中许多调节因子适应性的理解。
