RESPONSIVENESS OF THE AGING CIRCADIAN CLOCK TO LIGHT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal is to understand the basis of, and develop effective therapies for, chronic sleep disturbances in older adults. Chronic sleep disturbance is reported by nearly 50% of the elderly population. Common in this age group is an advance in the phase of sleep, accompanied by sleep maintenance insomnia and early morning awakenings. This can shorten the total sleep time and lead to daytime fatigue and impaired performance. The advance in sleep is associated with an advance in the timing of the circadian core body temperature (CBT) rhythm, indicating an advance in the timing of the circadian clock. The cause of the advance in phase is not known. However, preliminary data from our laboratory show that elderly subjects do not phase delay following exposure to light before the CBT minimum, a time that induces maximal delays in young subjects. The first goal of this proposal is to better understand the mechanism underlying this age-related change in responsiveness of the clock to light. Our long-term goal is to understand the basis of, and develop effective therapies for, chronic sleep disturbances in older adults. Chronic sleep disturbance is reported by nearly 50% of the elderly population. Common in this age group is an advance in the phase of sleep, accompanied by sleep maintenance insomnia and early morning awakenings. This can shorten the total sleep time and lead to daytime fatigue and impaired performance. The advance in sleep is associated with an advance in the timing of the circadian core body temperature (CBT) rhythm, indicating an advance in the timing of the circadian clock. The cause of the advance in phase is not known. However, preliminary data from our laboratory show that elderly subjects do not phase delay following exposure to light before the CBT minimum, a time that induces maximal delays in young subjects. The first goal of this proposal is to better understand the mechanism underlying this age-related change in responsiveness of the clock to light. The first Specific Aim will test the hypothesis that the circadian clock becomes less responsive to light with age. This hypothesis will be tested by comparing the magnitude of phase shifts of rhythms of melatonin, thyrotropin (TSH), and CBT in young and older adults following exposure to light at three different times (or phases) relative to the temperature minimum. The second Specific Aim will test the hypothesis that the phase response curve to light is altered with age. This hypothesis will be tested by plotting the direction and magnitude of phase shifts relative to the initial phase of melatonin, TSH, and CBT to generate the phase response curves to light. The direction and magnitude of phase shifts of the phase markers will be compared in young and older adults to determine whether age affects the phase dependent response of the clock to light. The second goal of this proposal is to assess whether it is possible to compensate for age-related changes in the responsiveness of the aging circadian clock to light, by increasing the intensity of the light exposure or by pharmacological treatment with the calcium channel antagonist nimodipine (Specific Aim 3). The proposed experiments will provide a vast amount of data in which to better understand the effect of age on circadian rhythms and sleep, and lead to improved treatments for circadian rhythm and sleep disorders in older adults.