AGING AND OXYGEN-TOXICITY - RELATION TO CHANGES IN MELATONIN

Melatonin (N-acetyl-5-methoxytryptamine) is a chemical mediator produc ed in the pineal gland and other sites in the body. The melatonin foun d in the blood is derived almost exclusively from the pineal gland. Si nce the pineal synthesizes melatonin primarily at night, blood levels of the indole are also higher at night (5-15 fold) than during the day . Some individuals on a nightly basis produce twice as much melatonin as others of the same age. Throughout life, the melatonin rhythm gradu ally wanes such that, in advanced age, melatonin production is usually at a minimum. Melatonin was recently found to be a free radical scave nger and antioxidant. It has been shown, in the experimental setting, to protect against both free radical induced DNA damage and oxidative stress-mediated lipid peroxidation. Pharmacologically, melatonin has b een shown to reduce oxidative damage caused by such toxins as the chem ical carcinogen safrole, carbon tetrachloride, paraquat, bacterial lip opolysaccharide, kainic acid, delta-aminolevulinic and amyloid beta pe ptide of Alzheimer's disease as well as a model of Parkinson's disease involving the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP ). Additionally, the oxidative damage caused by agents such as ionizin g radiation and excessive exercise is reduced by melatonin. Since free radical-induced molecular injury may play a significant role in aging , melatonin's ability to protect against it suggests a potential funct ion of melatonin in deferring aging and age-related, free radical-base d diseases. Besides its ability to abate oxidative damage, other benef icial features of melatonin may be important in combating the signs of aging; these include melatonin's immune-stimulating function, its sle ep-promoting ability, its function as an anti-viral agent, and general protective actions at the cellular level. Definitive tests of the spe cific functions of physiological levels of melatonin in processes of a ging are currently being conducted.