Cells discover fire: employing reactive oxygen species in development and consequences for aging

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.