Shifted light schedules and morbidity in mice

项目摘要：尽管轮班工作和穿越子午线旅行在我们的24/7中很常见， 在社会中，很少有对照研究讨论了重复的光照时间表变化对健康的影响 结果。最近我们有证据表明，老年啮齿动物的寿命受到影响， 重要的方式，通过改变白天/黑夜周期的时间来模拟穿越子午线的旅行，或者 人类轮流轮班工作。在3个目标中，我们建议使用小鼠模型来更好地理解 改变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 假设光周期的重复相位推进增加了老年小鼠的发病率。我们将确定 与长期暴露于改变的照明环境相关的特定器质性疾病，确定 最好地预测负面结果的受试者和照明环境的参数;以及确定 如果暴露于改变的光照环境对年幼的动物有害。在目标2中，我们将测试 假设在老年小鼠的相位提前期间，昼夜节律组织被破坏。使用分子 在大脑和外周组织的昼夜节律功能的指数，我们将确定在多大程度上改变 照明环境扰乱了年轻、中年和老年小鼠的昼夜节律组织。在目标3中， 测试睡眠中断是轮班相关死亡率和发病率的关键因素这一假设。使用 通过遥测EEG/EMG记录，我们将评估小鼠的睡眠行为，这些小鼠的睡眠时间经历了有规律的变化， 光的时间表。我们观察到的睡眠模式将在静止光照时间表的小鼠中进行模仿 使用诱导活动方法。我们将尝试将小鼠的死亡率和发病率与这种睡眠相关联 破坏时间表与在小鼠中观察到的相移时间表。 相关性：在美国，2004年抽样调查的工人中有14.8%报告说， 非标准轮班制此外，轮班工人中少数族裔的比例过高。 因此，了解与这些工作相关的健康后果是非常重要的 时间表，以便可以更改时间表或实施适当的医疗监测， 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.