MELATONIN, HYDROXYL RADICAL-MEDIATED OXIDATIVE DAMAGE, AND AGING - A HYPOTHESIS

Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical a nd provides on-site protection against oxidative damage to biomolecule s within every cellular compartment. Melatonin acts as a primary non-e nzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally relate d tryptophan metabolites are evolutionary conservative molecules princ ipally involved in the prevention of oxidative stress in organisms as different as algae and rats. The rate of aging and the time of onset o f age-related diseases in rodents can be retarded by the administratio n of melatonin or treatments that preserve the endogenous rhythm of me latonin formation. The release of excitatory amino acids such as gluta mate enhances endogenous hydroxyl radical formation. The activation of central excitatory amino acid receptors suppress melatonin synthesis and is therefore accompanied by a reduced detoxification rate of hydro xyl radicals. Aged animals and humans are melatonin-deficient and more sensitive to oxidative stress. Experiments investigating the effects of endogenous excitatory amino acid antagonists and stimulants of mela tonin biosynthesis such as magnesium may finally lead to novel therape utic approaches for the prevention of degeneration and dysdifferentiat ion associated with diseases related to premature aging.