EFFECTS OF AGING ON LIGHT-INDUCED PHASE-SHIFTING OF CIRCADIAN BEHAVIORAL RHYTHMS, FOS EXPRESSION AND CREB PHOSPHORYLATION IN THE HAMSTER SUPRACHIASMATIC NUCLEUS

Aging is associated with a variety of alterations in circadian rhythms , including changes in the response to environmental stimuli. The unde rlying causes for these age-related changes in the circadian system re main unknown. Recent studies have demonstrated that light induces the expression of Fos and phosphorylation of the cyclic-AMP response eleme nt-binding protein in the rodent suprachiasmatic nuclei, the location of a master circadian pacemaker in mammals, suggesting that these tran scription factors may mediate the effects of light on the circadian cl ock. The purpose of this study was to determine the effects of aging u pon light-induced phase-shifting of circadian locomotor activity rhyth ms, Fos protein expression and cyclic-AMP response element-binding pro tein phosphorylation in the suprachiasmatic nuclei. Young (three to fo ur months) and old (18-22 months) male golden hamsters free-running in constant darkness were exposed to 5-min monochromatic light pulses of different irradiance levels, at circadian time 19, after which either steady-state phase shifts of locomotor activity rhythms were measured , or else immunocytochemistry for Fos or for phospho-cyclic-AMP respon se element-binding protein was performed. Old hamsters were approximat ely 20 times less sensitive to the phase-shifting effects of light on the activity rhythm, and the photic irradiance threshold for Fos-like immunoreactivity induction in the suprachiasmatic nuclei was elevated when compared to young animals. Aging was also associated with a defic it in cyclic-AMP response element-binding protein phosphorylation by l ight. These data indicate that there are dramatic changes in light-act ivated molecular responses in the suprachiasmatic nuclei of old hamste rs, and suggest that these molecular changes may underlie age-related changes in the effects of light on the circadian clock system.