Shifted light schedules and morbidity in mice

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Project Summary: Despite the fact that shift work and transmeridian travel are commonplace in our 24/7 society, few controlled studies have addressed the effects of repeated light-schedule shifts on health outcomes. Recently we have obtained evidence indicating that longevity of aged rodents is affected, in significant ways, by changes in the timing of the day/night cycle simulating transmeridian travel or aspects of human rotating shift work. In 3 Aims we propose to use a mouse model to develop a better understanding of the health effects of altered lighting environments and of simulated shift work. In Aim 1 we will test the hypothesis that repeated phase-advances of the light-cycle increase morbidity in aged mice. We will identify specific organic disorders associated with long-term exposure to altered lighting environments, determine the parameters of the subjects and the lighting environment that best predict negative outcomes; and determine if exposure to altered lighting environments are harmful to younger animals. In Aim 2 we will test the hypothesis that circadian organization is disrupted during a phase-advance in aged mice. Using molecular indices of circadian function in brain and peripheral tissues, we will determine the extent to which altered lighting environments disrupt circadian organization in young, middle-aged, and old mice. In Aim 3 we will test the hypothesis that sleep disruption is a critical factor in shifting-related mortality and morbidity. Using telemetric eeg/emg recording, we will evaluate sleep behavior in mice that experience regular shifts in their light schedules. The sleep patterns we observe will then be mimicked in mice on stationary light schedules using an induced activity approach. We will attempt to correlate mortality and morbidity in mice on this sleep disruption schedule with that seen in mice on phase-shifting schedules. Relevance: In the United States, 14.8% of workers sampled in 2004 reported that they were currently working a non-standard shift schedule. Furthermore, minorities are overrepresented among shift workers. Therefore it is of great importance to understand the health consequences associated with these work schedules, so that schedules can be altered or appropriate medical monitoring can be implemented to reduce these risks.