Figure 1.

Reactive oxygen species formation and detoxification. Superoxide anion radicals (O₂˙‐) are mainly generated by the mitochondrial complexes I and III during electron transfer through the electron transport chain (ETC.). O₂˙‐ can interact with •NO, produced by nitric oxide synthase (NOS), to generate peroxynitrite (ONOO‐) or can also react to form •OH (hydroxyl radical). Detoxification involves the enzymatic activity of superoxide dismutase (SOD) that converts O₂˙‐ to H₂O₂ and may diffuse to the cytoplasmic compartment where glutathione peroxidase (GPX) and catalase convert H₂O₂ to H₂O. In physiological conditions, reactive oxygen species (ROS) production and detoxification are in balance. In aging, increase in ROS production and/or defects in the antioxidant system may induce oxidative stress leading to protein and DNA oxidation as well as lipid peroxidation, which can in turn affect the ETC. and exacerbate ROS production (dashed arrow). This may trigger a vicious cycle of oxidative stress that lead to cell death by apoptosis when a pathological threshold is passed (dashed line marked by *). eNOS/iNOS/nNOS; endothelial/inducible/neuronal nitric oxide synthase, GSH/GSSG; reduced/oxidized glutathione, GPX; glutathione peroxidase, GR; glutathione reductase, IMM; inner mitochondrial membrane.