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衰老的分子机制及当前对抗肌肉减少症的策略。

Molecular mechanisms in aging and current strategies to counteract sarcopenia.

作者信息

Sakuma Kunihiro, Yamaguchi Akihiko

机构信息

Research Center for Physical Fitness, Sports and Health, Toyohashi University of Technology, Toyohashi, Japan.

出版信息

Curr Aging Sci. 2010 Jul;3(2):90-101. doi: 10.2174/1874609811003020090.

Abstract

Sarcopenia, the progressive loss of muscle mass with age, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength and power. Sarcopenia is a highly significant public health problem. Since these age-related changes in skeletal muscle are largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostatis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. We and other researchers demonstrated that a disruption of Akt-mTOR and RhoA-SRF signaling but not Atrogin-1 or MuRF1 contributes to sarcopenia. In addition, sarcopenia seems to include a marked loss of fibers attributable to apoptosis. This review deals with molecular mechanisms of muscle atrophy and provides an update on current strategies (resistance training, myostatin inhibition, treatment with amino acids or testosterone, calorie restriction, etc) for counteracting this loss. Resistance training in combination with amino acid-containing nutrition would be the best candidate to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness.

摘要

肌肉减少症是指随着年龄增长肌肉质量逐渐丧失,其特征是肌肉数量和质量恶化,导致运动逐渐减慢以及力量和功率下降。肌肉减少症是一个非常重要的公共卫生问题。由于骨骼肌中这些与年龄相关的变化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,导致这些有害变化的机制为药物研发提供了众多治疗靶点。我们和其他研究人员证明,Akt-mTOR和RhoA-SRF信号通路的破坏而非Atrogin-1或MuRF1导致了肌肉减少症。此外,肌肉减少症似乎包括因细胞凋亡导致的明显纤维损失。本综述探讨了肌肉萎缩的分子机制,并提供了当前对抗这种损失的策略(抗阻训练、抑制肌生成抑制素、用氨基酸或睾酮治疗、热量限制等)的最新情况。抗阻训练与含氨基酸营养相结合将是减轻、预防或最终逆转与年龄相关的肌肉萎缩和虚弱的最佳选择。

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