Pineal gland and aging.

Advancing age is characterized by a progressive impairment of virtually all cognitive a.nd behavioral functions, and several degenerative changes, such as neuron loss, myelin degeneration, gliosis and neurotransmitter system ?ecline, are considered the hallmarks of the agmg brain. In accord with many studies, the steady decline in the weight of fixed brain appears as a function of age between 20 and 100 years, and neurotransmitter system changes widely involve the central nervous system (CNS), including cholinergic, aminergic and peptidergic ne.urons (1-3). In particular, a marked decrease m volume total cell number and number of vasopres~inergic cells was observed in suprachiasmatic nuclei (SCN) in subjects aged 80-100 years (3). . . . The notion that SCN are the major CIrcadian pacemaker of the mammalian brain, coordinating hormonal and behavioral circadian rhythms, has gained much support over the last decades (4). Circadian rhythms are a fundamental. feature of all living organisms, whose functional integrity not only depends on the maintenance of a constant internal milieu, but also on the maintenance of complex temporal relations between various oscillating variables at a cellular as well as an organic and organ-system level. The frequent occurrence of depression, the loss of reproductive capacity, as well as the decreased thermoregulatory ability, and, particularly, the fragmentation of sleep~V:'ak~ p~t­ terns suggest that circadian rhythmlclt.y IS ?ISrupted with aging at various levels of blol<?g~~al organization (5, 6). This supports the posslblhty that a decay in circadian organization may be involved in the gradual and progressive physiological deterioration that limits the lifespan (7, 8). Accordingly, the degenerative changes ~n SCN found in senescence and even more so m Alzheimer's disease (3, 9) may represent morphological correlates of the circadian rhythm disorder since SCN size has been shown to be directly ~elated to the expression of its pacemaker properties (10). On the other hand, the endogenously SCN controlled circadian timekeeping system is deeply influenced by the very stabl.e light-dar~ cycle, which plays an important role m the entramment of the circadian rhythms. The pineal gland by means of its hormone melatonin (aMT) is involved in transferring information on environmental day-length to the neuroendocrine system (11, 12). This review will first consider age-related morpho-functional changes in the pineal gland, and subsequently will examine present knowledge about the possible involvement of pineal gland decline in the general process of aging.