Department of Physiology, University of Texas Health Science Center at San Antonio, Texas, USA.
Integr Comp Biol. 2010 Nov;50(5):869-79. doi: 10.1093/icb/icq079. Epub 2010 Jul 2.
The oxidative stress theory and its correlate the mitochondrial theory of aging are among the most studied and widely accepted of all hypotheses of the mechanism of aging. To date, most of the supporting evidence for these theories has come from investigations using common model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and laboratory rodents. However, comparative data from a wide range of endotherms provide equivocal support as to whether oxidative stress is merely a correlate, rather than a determinant, of species' maximum lifespan. The great majority of studies in this area have been devoted to the relationship between reactive oxygen species and maximal longevity in young adult organisms, with little emphasis on mitochondrial respiratory efficiency, age-related alterations in mitochondrial physiology or oxidative damage. The advantage of studying a broader spectrum of species is the broad range of virtually every biological phenotype/trait, such as lifespan, body weight and metabolic rate. Here we summarize the results from a number of comparative studies in an effort to correlate oxidant production and oxidative damage among many species with their maximal lifespan and briefly discuss the pitfalls and limitations. Based on current information, it is not possible to accept or dispute the oxidative stress theory of aging, nor can we exclude the possibility that private mechanisms might offer an explanation for the longevity of exceptionally long-lived animal models. Thus, there is need for more thorough and controlled investigations with more unconventional animal models for a deeper understanding of the role of oxidative stress in longevity.
氧化应激理论及其相关的线粒体衰老理论是所有衰老机制假说中研究最多、最广泛接受的理论之一。迄今为止,这些理论的大多数支持证据来自于使用常见的模式生物(如秀丽隐杆线虫、黑腹果蝇和实验鼠)进行的研究。然而,来自广泛的恒温动物的比较数据对氧化应激是否仅仅是物种最大寿命的一个相关因素,而不是决定因素,提供了模棱两可的支持。该领域的绝大多数研究都致力于研究活性氧物种与年轻成年生物最大寿命之间的关系,而对线粒体呼吸效率、与年龄相关的线粒体生理学改变或氧化损伤的关注较少。研究更广泛的物种范围的优势在于,几乎每个生物学表型/特征(如寿命、体重和代谢率)都有很大的范围。在这里,我们总结了一些比较研究的结果,努力将许多物种的氧化剂产生和氧化损伤与它们的最大寿命相关联,并简要讨论了其中的陷阱和局限性。根据目前的信息,我们既不能接受也不能反驳衰老的氧化应激理论,也不能排除私人机制可能为异常长寿的动物模型的长寿提供解释的可能性。因此,需要对更多非传统的动物模型进行更深入和更严格的调查,以加深对氧化应激在长寿中的作用的理解。