Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species
Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species
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DOI：
10.1113/jphysiol.2011.206623
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发表时间：
2011-05-01
影响因子：
5.5
通讯作者：
McArdle, Anne
中科院分区：
文献类型：
--
作者：
Jackson, Malcolm J.;McArdle, Anne
骨骼肌在休息时产生超氧化物和一氧化氮，并且这种产生通过收缩活动增加。在年轻和成年动物和人类中，这些物种的活性增加以及源自它们的次级产物（活性氧，ROS）刺激氧化还原敏感的信号传导途径，以改变细胞保护性调节蛋白的细胞含量，例如防止组织氧化损伤的超氧化物歧化酶，过氧化氢酶和热休克蛋白。对收缩的这些适应性反应的潜在机制包括氧化还原敏感性转录因子如核因子κ B（NF κ B）、激活蛋白-1（AP 1）和热休克因子1（HSF 1）的激活。在衰老过程中，所有组织，包括骨骼肌，都表现出氧化损伤的积累，这可能导致组织稳态的丧失。这种增加的氧化损伤的原因是不确定的，但大量的数据表明，骨骼肌的能力，从老化的生物体响应增加的ROS产生的细胞保护蛋白的表达增加，通过激活氧化还原敏感的转录因子是严重减弱。这种与年龄相关的对由收缩活动诱导的ROS的生理适应的缺乏似乎有助于ROS稳态的丧失和骨骼肌中氧化损伤的增加。
Skeletal muscle generates superoxide and nitric oxide at rest and this generation is increased by contractile activity. In young and adult animals and man, an increase in activities of these species and the secondary products derived from them (reactive oxygen species, ROS) stimulate redox-sensitive signalling pathways to modify the cellular content of cytoprotective regulatory proteins such as the superoxide dismutases, catalase and heat shock proteins that prevent oxidative damage to tissues. The mechanisms underlying these adaptive responses to contraction include activation of redox-sensitive transcription factors such as nuclear factor kappa B (NF kappa B), activator protein-1 (AP1) and heat shock factor 1 (HSF1). During ageing all tissues, including skeletal muscle, demonstrate an accumulation of oxidative damage that may contribute to loss of tissue homeostasis. The causes of this increased oxidative damage are uncertain, but substantial data now indicate that the ability of skeletal muscle from aged organisms to respond to an increase in ROS generation by increased expression of cytoprotective proteins through activation of redox-sensitive transcription factors is severely attenuated. This age-related lack of physiological adaptations to the ROS induced by contractile activity appears to contribute to a loss of ROS homeostasis and increased oxidative damage in skeletal muscle.