Ageing and the free radical theory
Ageing and the free radical theory
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DOI：
10.1016/s0034-5687(01)00313-9
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发表时间：
2001-11-15
期刊：
影响因子：
--
通讯作者：
Wickens, AP
中科院分区：
文献类型：
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作者：
Wickens, AP
自由基理论认为，衰老是细胞和组织氧化损伤的累积结果，主要是有氧代谢的结果。有几条证据支持这一假说，包括：（1）物种寿命的变化与代谢率和保护性抗氧化活性相关;（2）实验动物抗氧化酶表达的增强可显著延长寿命;（3）细胞自由基损伤水平随年龄增加而增加;（4）动物体内抗氧化酶的表达水平随年龄增加而增加。以及（4）卡路里摄入量的减少导致活性氧物质产生的减少和寿命的增加。自由基理论也可以用来解释许多随着衰老而发展的结构特征，包括膜的脂质过氧化、老年色素的形成、蛋白质的交联、DNA损伤和线粒体功能的下降。尽管如此，关于氧化损伤在衰老中的作用仍然存在许多不确定性，不能排除其他解释。自由基在生物组织中仅以微量存在，它们的细胞水平和作用无法在体内测量，并且缺乏氧化分子是衰老的主要原因的确切证据。此外，老龄化也可能是一个多因素的过程，不能归结为任何一个单一的原因。因此，尽管自由基理论具有积极的特征，但其证据要么是相关的，要么是不确定的。(C)2001 Elsevier Science B. V.保留所有权利。
The free radical theory proposes that ageing is the cumulative result of oxidative damage to the cells and tissues of the body that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: (1) variation in species life span is correlated with metabolic rate and protective antioxidant activity; (2) enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity; (3) cellular levels of free radical damage increases with age; and (4) reduced calorie intake leads to a decline in the production of reactive oxygen species and an increase in life span. The free radical theory may also be used to explain many of the structural features that develop with ageing including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function. Despite this, many uncertainties concerning the role of oxidative damage in ageing remain and alternative explanations cannot be ruled out. Free radicals only occur in trace quantities in biological tissues, their cellular levels and actions cannot be measured in vivo, and definitive proof that oxidised molecules are the primary cause of ageing is lacking. Moreover, ageing is also likely to be a multifactorial process and not reducible to any one single cause. Thus, despite its positive features, the evidence for the free radical theory is either correlative or inconclusive. (C) 2001 Elsevier Science B.V. All rights reserved.