Melatonin as an antiaging drug: between facts and fantasy.

This contribution makes an attempt to critically reassess the impressive career of melatonin from a stepchild of hormone research to a best-seller of drug marketing. Melatonin is an extremely interesting hormone. It is involved in the regulation of seasonal and circadian fluctuations of other hormones and in the synchronization of many different aspects of circadian rhythmicity to the light-dark cycle. In addition to these receptor-mediated functions, melatonin may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals. Melatonin is also a potent scavenger of reactive oxygen species and may thus protect cells and tissues against radical-mediated damage. The production of melatonin declines with increasing age, and circulating melatonin levels are affected by certain pharmacological or physiological manipulations, notably food restriction which increases melatonin levels and prevents its age-related decline. Animal and cell culture experiments suggest that melatonin may have beneficial effects on certain aspects of aging and age-associated diseases. Of particular interest in this respect are reports on the influence of melatonin on the brain and the immune system. More research data are urgently needed in order to more clearly define the possible sites and mechanisms of these actions. Clinical studies need to be performed in order to identify possible side effects of long-term melatonin treatment, especially in elderly and diseased subjects. Serious concerns are raised about the use of uncontrolled, impure, or partially degraded melatonin preparations.