The interactions between molecular damage in cells, repair system activity, the generation of reactive oxygen species (ROS) in mitochondria capable of causing damage, and individual or species longevity are far from simple. The free radical theory of aging and its variants were early and in hindsight overly simplistic views based on the observation that the presence of ROS and their signs of their damage increase with age. However, numerous methods of slowing aging in short-lived animals involve increases in the rate at which mitochondria produce reactive oxygen species. These molecules are signals as well as sources of damage, and an increase can cause repair systems to overcompensate, producing a net gain in cellular maintenance and reduction in overall levels of damage. It isn't just repair: many of the benefits of exercise are also keyed to temporary increases in ROS levels.
Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the ageing process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artefacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect ageing and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan.
A topic highly debated in the field is the role that mitochondrial ROS play in age related and non-age related pathological processes with a mitochondrial component. Are ROS a cause or a consequence of mitochondrial dysfunction? This is a very important question, which needs to be addressed, since it will affect the treatment of those pathologies. Considering all the available evidence, it is plausible to suggest that ROS can have both positive and negative roles depending on the type of the ROS, when, where and how much is produced. Therefore, we can talk about "Good" and "Bad" ROS. "Good" ROS being low reactivity ROS (i.e. superoxide or hydrogen peroxide) produced at specific places, at specific times and in moderate amounts and "Bad" ROS being highly reactive ROS (or low reactive ROS as hydrogen peroxide or superoxide produced at high concentrations) generated continuously and unspecifically. Experimental evidence suggests that boosting ROS production can contribute to the maintenance of cellular homeostasis and positively affect lifespan when induced correctly, whereas if produced in excess or in an unspecific way, they shorten survival and accelerate the onset of age-related disease.