Melatonin, Neurogenesis, and Aging Brain

Aging is an irreversible process affecting all living organisms. During aging, all organs and tissues of the body reduce their functional capabilities, leading to a progressive loss of physical and cognitive performances. The loss of cells with age is directly related to apoptosis, a mechanism of cell death linked to mitochondrial failure. Attempting to understand the aging process, several theories have been proposed; among them, the mitochondrial free radical theory of aging is the one with more experimental evidence to date. Mitochondria are the source but also the target of these radicals, which produce their age-dependent slow and continuous damage. It is now recognized that mitochondrial impairment underlies not only the aging process but also many other age- associated pathologies, including neurodegenerative diseases, cancer, metabolic alteractions, etc. These diseases, mainly neurodegeneration, share mitochondrial dysfunction, oxidative/nitrosative stress and apoptosis in particular brain areas as a final common pathway. Consequently, neuronal loss may be associated to mitochondrial dysfunction in those disorders. Although the vast majority of cells in the adult brain are generated during the embryonic and early postnatal period, it is now apparent that some proportion of neurogenesis is also happening during adulthood. The functional significance of the adult neurogenesis is not fully understood and recent data point to a role of mitochondria in the process of stem cell differentiation. Thus, understanding mitochondrial function and regulation should be the first line of research to know how neurogenesis is regulated. Melatonin is an endogenous indoleamine take up by the mitochondria; once inside, melatonin promotes energy production and reduces free radical generation, thus preventing mitochondrial damage. These functions of melatonin seem to be related to the neurogenesis promoting role of the indoleamine. The physiological and pathophysiological meanings of these functions of melatonin are also revised here.