ABSTRACT
Ever since Harmon published his provocative hypotheses of aging (Harman, 1956, 1972), oxidative stress has been considered a cause of aging. In this chapter we borrow a lesson from weed science to explain the nature of and, in this case, the lethal power of an oxidative chain reaction. Paraquat is widely used in the eld of aging as a powerful oxidative poison causing a chain reaction of destruction and death in organisms ranging from weeds and Caenorhabditis elegans to humans. Paraquat, used by farmers as a broad-spectrum herbicide, has the dubious distinction of being the method of choice for suicide in some countries. This weed killer is inexpensive, and 10 ml of the concentrate can be lethal to humans. Susceptibility to paraquat has been linked to membrane unsaturation levels (Section II). Paraquat is a powerful oxidative toxin in plants and animals, acting as a free radical and short-circuiting highenergy electrons generated during cellular metabolism. The net effect is generation of scorching amounts of reactive oxygen species (ROS), which destroy essential cellular components. Electrons pass from paraquat to oxygen via a chemical reaction and yield one of the most potent chemical toxins found in cells-superoxide radical, in which the oxidative power of O2 is greatly enhanced after acquiring an additional electron. Superoxide radical is a free radical, and thus paraquat catalyzes formation of free radicals using oxygen as substrate. Superoxide forms even more toxic derivatives, which can chemically attack most cellular constituents, including membranes, proteins, and DNA. Superoxide is a member of a class of naturally occurring reactive oxygen species or free radicals. According to Harman’s hypothesis (Harman, 1956, 1972), the continuous destruction of critical cellular components in human cells by free radicals is a cause of aging and age-related diseases. With acute paraquat poisoning it is suggested that a chain reaction of oxidative stress overpowers defenses against oxidative damage, causing rapid-re cellular death that can quickly spread to destroy functions of vital organs and cause death.
