SLEEP AND WAKE RHYTHMS IN AGING--RESPONSIVENESS OF CLOCK TO LIGHT

$0M01FY2001RRNIH

Northwestern University, Evanston IL

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Abstract

Our long term goal is to understand the basis of and develop effective therapies for chronic sleep disturbances in older adults. Age-related changes in the endogenous circadian pacemaker, combined with reduced exposure to light during the day, may contribute to disruptions of sleep/wake rhythms in the elderly. Timed exposure to bright light can improve sleep efficiency and daytime performance in older adults. However, recent results in animal models of aging suggest that the effectiveness of light therapy for the treatment of sleep disorders may be limited by reduced responsiveness of the aging clock to light. While the circadian timing system of old rodents shows reductions in responsiveness to light, it is not known whether the human clock exhibits similar changes with age. The hypothesis is that the responsiveness to light is decreased in the elderly will be tested by assessing the light-induced suppression of nocturnal melatonin levels and phase shifts of the circadian temperature and melatonin rhythms in young and old subjects. In addition, animal studies indicate that the reduction of responsiveness to light by the aging pacemaker may be due to impaired regulation of calcium homeostasis. Treatments that decrease intracellular calcium levels, such as the calcium channel antagonist nimodipine, have been shown to exhibit neuroprotective effects, improve neural plasticity and reverse aging-associated declines in motor and cognitive performance. Preliminary results indicate that calcium channel antagonists can also restore the responsiveness of the clock to light, since nimodipine increases the magnitude of phase shifts of circadian activity rhythms following exposure to light in old mice. Therefore, the results from this study, in combination with results from ongoing studies in rodents, will suggest whether nimodipine might also enhance the effectiveness of light on phase shifts of circadian rhythms in older adults. These studies will advance the long term goal of this project, which is to determine whether nimodipine can enhance the effectiveness of light therapy for the treatment of sleep/wake disorders in the elderly.

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