Hormones and Antiaging Medicine: Melatonin and Antiaging

Melatonin is a hormone synthesized from tryptophan via serotonin. How the clock information of the suprachiasmatic nucleus (the main clock) is transmitted to the pineal gland is shown in Fig. 49.1 [1]. The oscillations produced by the transcription/translation feedback mechanism of the so-called “clock genes” such as Clock, Bmal1, Per, Cry, etc., expressed in the suprachiasmatic nucleus, are not exactly 24 h, but a 24 ± 4 h cycle, hence they are called circadian clocks, and each species shows its own unique cycle. This clock mechanism is precisely synchronized to a 24-h cycle by stimuli from the outside world that follow a 24-h cycle (synchronizing factors). In other words, the 24-h light information received by the retina is transmitted to the suprachiasmatic nucleus, aligning the phase of the body clock with the outside world and synchronizing the clock cycle to a 24-h cycle. Next, the time information generated in the suprachiasmatic nucleus stimulates the pineal gland cells only at night via norepinephrine (NE), resulting in the activation of arylalkylamine N-acetyltransferase (AANAT), the rate-limiting enzyme for melatonin synthesis. On the other hand, during the day, NE is not secreted, so AANAT is hardly synthesized, and as a result, the concentration of melatonin in the blood shows a clear diurnal variation, being low during the day and high at night. This clear diurnal rhythm of melatonin is observed not only in the blood but also in all body fluids such as cerebrospinal fluid, saliva, aqueous humor, follicular fluid, and even breast milk. In other words, melatonin is a messenger that transmits the “night” time information to the whole body under the command of the body clock.