Reactive oxygen species (ROS) and other free radicals are unstable chemicals that constitute an important part of our normal metabolism. However, greater concentrations of these chemicals are implicated in a wide spectrum of age-related pathologies from inflammation to dementia. Could it be that the generation of toxic levels of these chemicals forms an integral component of the aging process?
Free radicals are defined as molecules having an unpaired electron in their valence shell; simply put, they are electrically unstable. This leads them to either rip electrons from, or donate electrons to, nearby molecules, often resulting in a chain reaction by converting these other molecules into free radicals.
Despite the crucial role of free radicals in the normal functioning of our cells, too many of them can have devastating effects. Artificially inducing high concentrations of free radicals will result in rampant electron swapping to the extent that the cell simply shuts down the normal processe and the cell will undergo necrosis or apoptosis. Alternatively, if lower levels of free radicals are consistently present over longer periods of time, resulting damage can accumulate to result in comparable damage to cellular components and processes. Mutations in DNA can result, that if in certain regions of our genome can result in a range of subsequent pathologies, from cell death to carcinogenesis. Thus, if over time we loss control over the concentration of free radicals in our bodies, it could very well explain the symptoms we normally associate with aging.
Do free radicals play such a role in aging? One reason that it is hard to ascertain whether or not this is so is because it is difficult to detect the levels of free radicals in vivo. Present methodologies for detecting free radicals are for the most part crude, and thus yield ambiguous data with regard to how important these processes are with aging. However,some compelling evidence does exist that free radicals play an important part of aging. There is evidence that mitochondrial genome mutations increase with age, some leading to drastic increases in intracellular concentrations of free radicals. This purported age-related increase in free radical production due to mitchondria failing could thus very well lead to an increase in the incidence of many of the aforementioned diseases. Alternatively, DNA mutations in genes regulating the concentrations of free radicals could likewise result in a feedback loop to induce more free radicals and exacerbate damage.
Current evidence thus suggests that free radicals are an important part of aging, but by no means established their role as central to the process. That is, other forms of cellular dysfunction, such as mitochondrial dysfunction or DNA mutations, likely precede free radical production and thus the generation of free radicals is simply the secondary medium whereby these other forms of dysfunction cause visible age-related pathologies. This implies that intervening at the free radical stage, via antioxidants or other therapies, could theoretically attenuate age-related damage and pathologies, but not to the extent that treating the underlying initial causes would yield. Experimental evidence supports this hypothesis.
Many researchers have touted the potential of antioxidants in extending lifespan, but no antioxidant has been demonstrated to accomplish this. While the longevity of some inbred or deficient mutant organisms has been extended via such pharmacological interventions, this by no means translates into life extension in wildtype organisms. More likely, the antioxidants compensate for the genetic defects.
The development of future life-extension therapies therefore probably lies in addressing the factors responsible for the increase in free radical damage associated with age rather than attenuating the free radicals themselves.