Alterations in the circadian system in advanced age

In addition to light, a variety of non-photic stimuli can induce phase shifts in the circadian clock of rodents. We have examined the effects of advanced age on the response of the circadian clock to both photic and non-photic stimuli in old hamsters (i.e., over 16 months of age). Among the age-related changes in the circadian rhythm of locomotor activity are: (1) alterations in the phase angle of entrainment to the light-dark cycle; (2) an altered response to the phase-shifting effects of light pulses; (3) changes in the time it takes to re-entrain to a new light-dark cycle; and (4) a loss of responsiveness to the phase-shifting or entraining effects of stimuli which induce an acute increase of activity. Many of the effects of ageing on the circadian clock system can be simulated in young animals by depleting brain monoamine levels, suggesting that ageing 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 suprachiasmatic nuclear tissue. Determining the physiological basis of age-related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian functioning can be restored, should lead to new insight into the functioning of the circadian clock and may suggest new approaches to the normalization of disturbed circadian rhythms.