Muller Florian L, Lustgarten Michael S, Jang Youngmok, Richardson Arlan, Van Remmen Holly
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Free Radic Biol Med. 2007 Aug 15;43(4):477-503. doi: 10.1016/j.freeradbiomed.2007.03.034. Epub 2007 Apr 10.
The early observations on the rate-of-living theory by Max Rubner and the report by Gershman that oxygen free radicals exist in vivo culminated in the seminal proposal in the 1950s by Denham Harman that reactive oxygen species are a cause of aging (free radical theory of aging). The goal of this review is to analyze recent findings relevant in evaluating Harman's theory using experimental results as grouped by model organisms (i.e., invertebrate models and mice). In this regard, we have focused primarily on recent work involving genetic manipulations. Because the free radical theory of aging is not the only theorem proposed to explain the mechanism(s) involved in aging at the molecular level, we also discuss how this theory is related to other areas of research in biogerontology, specifically, telomere/cell senescence, genomic instability, and the mitochondrial hypothesis of aging. We also discuss where we think the free radical theory is headed. It is now possible to give at least a partial answer to the question whether oxidative stress determines life span as Harman posed so long ago. Based on studies to date, we argue that a tentative case for oxidative stress as a life-span determinant can be made in Drosophila melanogaster. Studies in mice argue for a role of oxidative stress in age-related disease, especially cancer; however, with regard to aging per se, the data either do not support or remain inconclusive on whether oxidative stress determines life span.
马克斯·鲁布纳（Max Rubner）早期对生活速率理论的观察以及格什曼（Gershman）关于体内存在氧自由基的报告，最终促成了20世纪50年代丹纳姆·哈曼（Denham Harman）提出的开创性观点，即活性氧是衰老的一个原因（衰老的自由基理论）。本综述的目的是利用按模式生物（即无脊椎动物模型和小鼠）分类的实验结果，分析与评估哈曼理论相关的最新发现。在这方面，我们主要关注了近期涉及基因操作的研究。由于衰老的自由基理论并不是为解释分子水平上衰老所涉及的机制而提出的唯一理论，我们还讨论了该理论与生物老年学其他研究领域的关系，特别是端粒/细胞衰老、基因组不稳定性和衰老的线粒体假说。我们也讨论了我们认为自由基理论的发展方向。现在至少可以部分回答哈曼很久以前提出的氧化应激是否决定寿命的问题。基于迄今为止的研究，我们认为在黑腹果蝇中可以初步证明氧化应激是寿命的决定因素。对小鼠的研究表明氧化应激在与年龄相关的疾病，尤其是癌症中起作用；然而，就衰老本身而言，关于氧化应激是否决定寿命的数据要么不支持，要么仍然没有定论。
