Melatonin, Oxidative Stress, and the Aging Brain

Abstract

The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.