The Decrease of Pineal Melatonin Production with Age

Aging has been defined as a general decline in organic functions as well as a decrease in adaptiveness to change and to restore disrupted homeostasis.In the last few years it has been established that circadian rhythms observed in, e .g ., endocrine, behavioral and anatomical processes were a fundamental feature of living 0rganisms.lIn addition to the classical concept of homeostasis it is now recognized that the functional integrity of organisms also depends on the maintenance of relations between various oscillating variables at the cellular level of organs and organ-systems.The suprachiasmatic nuclei (SCN) have been established as the circadian pacemaker of the mammalian brain.It has become increasingly clear that a desynchronization between the activity of the SCN and the activity of the subject, either experimentally induced or as a result of shift work or jet lag, results in severe cognitive, emotional and endocrine disturbances.'Within this framework, Samis' hypothesized that the gradual and progressive deterioration of functional potential, which is the ubiquitous hallmark of aging, is the result of the loss of coordination among the many interdependent oscillating systems.Furthermore, Pittendrigh and Daan4 suggested that a decay of circadian organization may be involved in the programmed physiological deterioration that limits lifespan.This hypothesis of "loss of circadian rhythmicity in aging" is supported by numerous animal studies.Little is known, however, about how the central nervous system correlates the senescence-related changes in circadian rhythms.However, as it is now well established that in mammals, the pineal gland by its rhythmic secretion of melatonin and the SCN play an essential role in the regulation of these rhythmic functions, it is probable that the disfunctioning of one of these structures, or both of them, is at the root of these disturbances.With respect to the pineal gland, reported to be a circadian or seasonal aging clock,' aging coincides with several functional and morphological alteration^.^-'Decrease of secretory processes8 and particularly of nocturnal melatonin synthesis was reported to occur in rodents during aging.9-"'~s~'1A disappearance of daynight rhythm of melatonin in old and Alzheimer's patients has been reported by Skene.l*A decrease of pineal activity,I3 a reduction of adrenergic innervation as well as a reduction of the number of pinealocytes has been reported in old male rats.14However, the cause of this melatonin production is not clear.We reported in a recent paper the increase in the calcium content of pineal glands of aging rats 43