Melatonin: a chronobiotic with anti-aging properties?

Recently, it has been reported that melatonin administration extends the lifespan of mice, a finding which supports previous research on the effects of pinealectomy and pineal extract administration. The prolongation of lifespan by melatonin has been interpreted in favour of an upregulation of the immune system as well as due to anti-stress properties of melatonin acting via the brain opioid system. In this paper we offer an alternative explanation of melatonin's anti-aging effect: the circadian pacemaker system has a diminished amplitude with age as indexed by a decrease in circulating melatonin levels. Stability of the circadian system correlates with its amplitude and loss of circadian amplitude produces lability which, in turn, leads to internal temporal disorder. Internal temporal disorder may be a precursor of disease states. Exogenous melatonin increases the amplitude of the circadian pacemaker system by feedback onto that system. The hypothalamic suprachiasmatic nuclei are thought to be the mammalian biological clock in the brain and have high concentrations of melatonin receptors. Therefore, melatonin administration in pharmacological doses may prevent aging symptoms by acting at the level of the circadian pacemaker's amplitude.