Pineal versus extrapineal melatonin in aging

Aging is a multifactorial process involving changes in cells and organs functions that led to a reduction in cognitive and physical activities as we get older. Because the biological clock and its main endocrine efferent, melatonin produced by the pineal gland, controls the body cell functions through the synchronization of their circadian functions, it is easily under understandable that an alteration of the former may affect significantly the efficiency of all physiological systems. Moreover, most, if not all, organs and tissues of the body synthetizes melatonin, the so-called extrapineal melatonin, which serves as a protective molecule to avoid the damage of these tissue during their metabolic function. It is now known that melatonin is synthetized by the mitochondria, and protects them from the oxidative damage during their normal function. But melatonin also acts on the cell nucleus to control the expression of a series of genes closely linked to the antioxidant and anti-inflammatory defense, and to the mitochondrial biogenesis. Aging, which is related to a mitochondrial deterioration and melatonin production decrease, may well reflect the loss of the protective role of melatonin, both pineal and extrapineal, thus facilitating the aging process itself. This review focus on the production, regulation, and functions of pineal and extrapineal melatonin, and their relationship with aging and agerelated diseases. Finally, the antioxidant, anti-inflammatory, and mitochondrial boost properties of melatonin have been used to prevent/counteract many of the age and age-dependent changes including neurodegenerative diseases. The efficacy of melatonin as neuroprotective agent is also revised here.