Age-dependent changes in the circadian system of the mouse will be examined as a model of the same changes in man. The disintegration of the circadian rhythm of sleep-wakefulness in the age and exercise (wheel-running) restriction experiments documented in our previous grant will be studied in greater detail. The body temperature rhythm will be added to the existing automated EEG scoring system to enable assessment or the phase relationships among the sleep/wake, activity, and body temperature rhythms both during the aging process and during exercise restriction in young and aged mice. An additional activity measurement will be added to provide an index of activity during the exercise restriction experiments. We also intend to: 1) examine the temporal order among the sleep/wake, body temperature, activity and drinking rhythms in young and old animals as well as in exercise-restricted animals; 2) directly test the hypothesis that the age and exercise-restriction effects on the sleep/wake rhythm are mediated through the circadian system; 3) attempt to ameliorate the age-dependent decay in the sleep/wake rhythm by restricting wheel availability to a specific time of day; 4) evaluate whether the young mouse exhibits a circadian phase-dependent sensitivity to exercise restriction; 5) examine whether the deterioration of the sleep/wake rhythm in the aged animal is accompanied by a decrement in the benzodiazepine receptor rhythm; 6) measure local cerebral glucose metabolism using the [14C] 2-deoxyglucose technique in young and aged mice to attempt to identify the neural basis of the age-dependent decay or circadian organization, with particular attention to the metabolic activity of the suprachiasmatic nucleus (SCN); and 7) attempt to consolidate the sleep/wake rhythm in an animal whose circadian system has been experimentally disrupted by lesion of the SCN. We anticipate that these experiments will elucidate mechanisms underlying the age-dependent decay of circadian organization in the mouse and that these principles should be generalizable to sleep disturbances observed in aged humans.
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