The free radical theory of aging (FRTA) states that organisms age because cells accumulate free radical damage over time.A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals such as melanin are not chemically reactive, most biologically-relevant free radicals are highly reactive.For most biological structures, free radical damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.
Strictly speaking, the free radical theory is only concerned with free radicals such as superoxide ( O2- ), but it has since been expanded to encompass oxidative damage from other reactive oxygen species such as hydrogen peroxide (H2O2), or peroxynitrite (OONO-).
Denham Harman first proposed the free radical theory of aging in the 1950s,and in the 1970s extended the idea to implicate mitochondrial production of reactive oxygen species.
In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan. In mice, interventions that enhance oxidative damage generally shorten lifespan.However, in roundworms (Caenorhabditis elegans), blocking the production of the naturally occurring antioxidant superoxide dismutase has recently been shown to increase lifespan.Whether reducing oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question.