Shifted light schedules and morbidity in mice

项目摘要：尽管轮班工作和跨子午线旅行在我们的全天候工作中司空见惯 在社会上，很少有对照研究讨论反复改变日程表对健康的影响 结果。最近我们获得的证据表明，老年啮齿动物的寿命受到影响，在 通过改变昼夜循环的时间来模拟穿越子午线的旅行或 人类轮班工作。在三个目标中，我们建议使用小鼠模型来更好地理解 改变的照明环境和模拟轮班工作对健康的影响。在目标1中，我们将测试 假设光周期的重复阶段推进会增加老龄小鼠的发病率。我们将确定 与长期暴露在改变的照明环境中相关的特定有机疾病，决定了 最能预测负面结果的受试者和照明环境的参数；并确定 如果暴露在改变的光照环境中对年幼的动物有害。在目标2中，我们将测试 在老龄小鼠的一个阶段进展中，昼夜节律组织被打乱的假说。使用分子 脑和周围组织的昼夜节律功能指标，我们将确定改变的程度 光照环境打乱了幼年、中年和老年小鼠的昼夜节律。在《目标3》中，我们将 测试睡眠中断是导致轮班相关死亡率和发病率的关键因素这一假设。vbl.使用 遥测脑电/肌电记录，我们将评估经历规则变化的小鼠的睡眠行为 轻松的日程表。然后，我们观察到的睡眠模式将在固定光照时间表的小鼠身上模拟 使用诱导活动的方法。我们将尝试在这种睡眠状态下将小鼠的死亡率和发病率联系起来 干扰时间表与在相移时间表上在老鼠身上看到的一样。 相关性：在美国，在2004年抽样调查的工人中，14.8%的人报告说他们目前 按照非标准的排班表工作。此外，少数族裔在轮班工人中的比例过高。 因此，了解与这些工作相关的健康后果非常重要 时间表，以便可以更改时间表或实施适当的医疗监测，以 降低这些风险。

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.