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硫醇/二硫键氧化还原状态的衰老相关变化:对硫醇抗氧化剂应用的启示

Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants.

作者信息

Dröge Wulf

机构信息

Deutsches Krebsforschungszentrum, German Cancer Research Center (DKFZ), Division of Immunochemistry, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

出版信息

Exp Gerontol. 2002 Dec;37(12):1333-45. doi: 10.1016/s0531-5565(02)00175-4.

Abstract

Genetic and biochemical studies suggest that free radical-derived reactive oxygen species play a key role in a common mechanism of aging in many or all animal species. This led to the hypothesis that the quality of life in old age may be improved by pharmacological or dietary thiol antioxidants. This review describes important details about how the organism deals with its own thiol antioxidants. Aging was found to be associated with an oxidative shift in the thiol/disulfide redox state (REDST) of the intracellular glutathione pool and of the plasma cyst(e)ine and albumin pools. There is also a decrease in plasma thiol (mainly cysteine) concentration. The oxidative shift in intracellular REDST was found to be typically associated with cellular dysfunctions. Studies in humans related to plasma REDST revealed correlations with aging-related pathophysiological processes, suggesting that oxidative changes in REDST play a key role in processes and diseases which limit the human life span. The age-related shift in plasma REDST is mediated, at least partly, by the decreasing capacity to remove dietary cysteine from the oxidative environment of the blood. Thiol antioxidants were found to ameliorate various aging-related processes but obviously ought to be used with caution in consideration of the oxidative environment of the blood.

摘要

遗传和生物化学研究表明,自由基衍生的活性氧在许多或所有动物物种的常见衰老机制中起关键作用。这引发了一种假说,即老年生活质量可能通过药理学或膳食硫醇抗氧化剂得到改善。这篇综述描述了生物体如何处理自身硫醇抗氧化剂的重要细节。研究发现,衰老与细胞内谷胱甘肽池以及血浆半胱氨酸和白蛋白池的硫醇/二硫键氧化还原状态(REDST)的氧化转变有关。血浆硫醇(主要是半胱氨酸)浓度也会降低。细胞内REDST的氧化转变通常与细胞功能障碍有关。在人类中与血浆REDST相关的研究揭示了其与衰老相关病理生理过程的相关性,表明REDST的氧化变化在限制人类寿命的过程和疾病中起关键作用。血浆REDST与年龄相关的转变至少部分是由从血液氧化环境中清除膳食半胱氨酸的能力下降介导的。已发现硫醇抗氧化剂可改善各种与衰老相关的过程,但考虑到血液的氧化环境,显然应谨慎使用。

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