Free-radical theory of aging

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The free radical theory of aging states that organisms age because cells accumulate free radical damage over time.^[1] A free radical is any atom or molecule that has a single unpaired electron in an outer shell.^[2] While a few free radicals such as melanin are not chemically reactive, most biologically relevant free radicals are highly reactive.^[3] 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.^[4]

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 (ROS) such as hydrogen peroxide (H₂O₂), or peroxynitrite (OONO⁻).^[4]

Denham Harman first proposed the free radical theory of aging in the 1950s,^[5] and in the 1970s extended the idea to implicate mitochondrial production of ROS.^[6]

In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan.^[7] However, in mice, only 1 of the 18 genetic alterations (SOD-1 deletion) that block antioxidant defences, shortened lifespan.^[8] Similarly, in roundworms (Caenorhabditis elegans), blocking the production of the naturally occurring antioxidant superoxide dismutase has been shown to increase lifespan.^[9] Whether reducing oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question.