Oxidative stress and ageing:: is ageing a cysteine deficiency syndrome?
Oxidative stress and ageing:: is ageing a cysteine deficiency syndrome?
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DOI：
10.1098/rstb.2005.1770
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发表时间：
2005-12-29
影响因子：
6.3
通讯作者：
Dröge, W
中科院分区：
文献类型：
--
作者：
Dröge, W
活性氧（ROS）在生物组织中不断产生，并在各种信号转导途径中发挥作用。异常高的ROS浓度引起与组织损伤和生理信号失调相关的氧化应激。越来越多的证据表明，氧化应激随着年龄的增长而增加。研究还表明，蠕虫、苍蝇和小鼠的寿命可以通过阻碍胰岛素受体信号级联的突变而显著延长。分子研究表明，胰岛素受体的胰岛素非依赖性基础活性被ROS增加，并被某些抗氧化剂下调。补充临床研究证实，补充谷胱甘肽前体半胱氨酸降低空腹状态下的胰岛素反应性。在几项临床试验中，补充半胱氨酸改善了骨骼肌功能，降低了体脂/瘦体重比，降低了炎症细胞因子turnout necrosis factor alpha（TNF-α）的血浆水平，改善了免疫功能，并增加了血浆白蛋白水平。由于所有这些参数都随着年龄的增长而退化，这些研究结果表明：（i）青春，健康和生活质量的丧失可能部分由半胱氨酸的缺乏来解释，（ii）半胱氨酸的饮食消费通常是次优的，每个人都可能迟早有半胱氨酸缺乏症。
Reactive oxygen species (ROS) are constantly produced in biological tissues and play a role in various signalling pathways. Abnormally high ROS concentrations cause oxidative stress associated with tissue damage and dysregulation of physiological signals. There is growing evidence that oxidative stress increases with age. It has also been shown that the life span of worms, flies and mice can be significantly increased by mutations which impede the insulin receptor signalling cascade. Molecular studies revealed that the insulin-independent basal activity of the insulin receptor is increased by ROS and downregulated by certain antioxidants. Complementary clinical studies confirmed that supplementation of the glutathione precursor cysteine decreases insulin responsiveness in the fasted state. In several clinical trials, cysteine supplementation improved skeletal muscle functions, decreased the body fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine turnout necrosis factor alpha (TNF-alpha), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate with age, these findings suggest: (i) that loss of youth, health and quality of life may be partly explained by a deficit in cysteine and (ii) that the dietary consumption of cysteine is generally suboptimal and everybody is likely to have a cysteine deficiency sooner or later.