The<unk>  (FRTA) states that organisms age because cells accumulate<unk><unk>  damage over time. A<unk><unk>  is any atom or molecule that has a single unpaired electron in an outer shell. While a few<unk><unk> s such as melanin are not chemically reactive, most biologically relevant<unk><unk> s are highly reactive. For most biological structures,<unk><unk>  damage is closely associated with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from<unk><unk> s. Strictly speaking, the<unk><unk><unk>  is only concerned with<unk><unk> s 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−). Denham Harman first proposed the<unk>  in the 1950s, and in the 1970s extended the idea to implicate mitochondrial production of ROS. In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan. However, in mice, only 1 of the 18 genetic alterations (SOD-1 deletion) that block antioxidant defences, shortened lifespan. Similarly, 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.
Free-radical theory of aging
Network theory of aging
Protein carbonylation
Chronic endothelial injury hypothesis
Genetics of aging
Lead–crime hypothesis
Protein leverage hypothesis
Epigenetics of neurodegenerative diseases