Effects of age on the circadian system.

While aging has been associated with changes in the period and amplitude of circadian rhythms, little is known about how aging influences the response of the circadian clock to environmental stimuli. In this paper, we report on recent studies designed to determine the effects of advanced age on the response of the circadian clock to both photic and nonphotic stimuli in old hamsters (e.g., over 16 mo of age). Among the most pronounced age-related changes in the circadian rhythm of locomotor activity are: (a) alterations in the phase-angle of entrainment to the light-dark cycle; (b) an increase in the magnitude of phase shifts induced by pulses of light presented at specific circadian times; and (c) a loss of responsiveness to the phase shifting or entraining effects of stimuli which induce an acute increase of activity. Depletion of brain monoamine levels in young animals can induce changes in the responsiveness of the circadian clock to environmental stimuli which are similar to those which occur spontaneously in old animals, suggesting that aging alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal SCN tissue. Determining the physiological basis for age related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian function can be restored, should lead to new insight into the functioning of the circadian clock and may lead to new approaches for normalizing disturbed circadian rhythms.