de Magalhães João Pedro, Church George M
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB238, Boston, MA 02115, USA.
Exp Gerontol. 2006 Jan;41(1):1-10. doi: 10.1016/j.exger.2005.09.002. Epub 2005 Oct 12.
The free radical theory of aging states that aging results from the accumulated damage caused by reactive oxygen species (ROS). Herein, we provide a critique of the theory that aims to point out the theory's weaknesses and put forward ideas for how future experiments must adjust to several emerging concepts. In the same way fire is dangerous and nonetheless humans learned how to use it, it now appears that cells evolved mechanisms to control and use ROS. The way ROS are used as signaling molecules in many crucial biological functions suggests ROS are not unwanted by-products of metabolism. We hypothesize that the connection between ROS and cellular processes like growth, proliferation, and apoptosis may explain why long-lived animals appear to have lower levels of ROS production: the longer development of long-lived animals may lead to lower steady state levels of ROS. With age, antioxidant systems become deregulated, just like so many other cellular components, and so oxidative damage occurs. Therefore, the production of ROS is not merely a cause of havoc but rather a complex and critical system whose disruption in disease and aging leads to oxidative damage. Potential roles of ROS in aging are discussed under this model.
衰老的自由基理论认为，衰老是由活性氧（ROS）造成的累积损伤所致。在此，我们对该理论进行批判，旨在指出其弱点，并针对未来实验如何适应几个新出现的概念提出想法。正如火是危险的，但人类学会了如何利用它一样，现在看来细胞进化出了控制和利用ROS的机制。ROS在许多关键生物学功能中用作信号分子的方式表明，ROS并非新陈代谢中不需要的副产物。我们推测，ROS与生长、增殖和凋亡等细胞过程之间的联系，或许可以解释为什么长寿动物的ROS产生水平似乎较低：长寿动物较长的发育过程可能导致ROS的稳态水平较低。随着年龄增长，抗氧化系统如同许多其他细胞成分一样失调，于是发生氧化损伤。因此，ROS的产生不仅仅是破坏的原因，而是一个复杂且关键的系统，其在疾病和衰老过程中的失调会导致氧化损伤。在此模型下讨论了ROS在衰老中的潜在作用。
