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Influence of Chronic Exposure to Simulated Shift Work on Disease and Longevity in Disease-Prone Inbred Mice

机译:慢性暴露于疾病 - 易受血液近亲小鼠疾病和寿命的模拟转变工作的影响

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摘要

Shift work (SW) is viewed as a risk factor for the development of many serious health conditions, yet prospective studies that document such risks are rare. The current study addressed this void by testing the hypothesis that long-term exposure to repeated diurnal phase shifts, mimicking SW, will accelerate disease onset or death in inbred mice with genetic risk of developing cancer, diabetes, or autoimmune disease. The data indicate that 1) life-long exposure to simulated SW accelerates death in female cancer prone AKR/J mice; 2) a significant proportion of male NON/ShiLtJ mice, which have impaired glucose tolerance but do not normally progress to type 2 diabetes, develop hyperglycemia, consistent with diabetes (that is, blood glucose 250 mg/dL or greater) after exposure to simulated SW for 8 wk; and 3) MRL/Mpj mice, which are prone to develop autoimmune disease, showed sex-related acceleration of disease development when exposed to SW as compared with mice maintained on a stable photocycle. Thus, longterm exposure to diurnal phase shifts that mimic SW reduces health or longevity in a wide variety of disease models. Our approach provides a simple way to assess the effect of chronic diurnal disruption in disease development in at-risk genotypes.
机译:转移工作(SW)被视为发展许多严重健康状况的危险因素,但潜在的研究表明这种风险是罕见的。目前的研究通过测试了这种假设来解决了这种无效,即长期暴露于重复的昼夜相移,模拟SW,将加速疾病发作或死亡的近亲小鼠,具有发展癌症,糖尿病或自身免疫疾病的遗传风险。数据表明,1)终原暴露于模拟SW加速死亡,易于易于Akr / J小鼠; 2)大部分雄性非/ shillj小鼠,葡萄糖耐受性损害但通常不适用于2型糖尿病,伴有糖尿病(即,血糖250mg / dl或更大)在暴露于模拟后呈糖尿病(即血糖250mg / dl或更大)。 SW为8周; 3)与维持在稳定的光细环上的小鼠相比,易于发展自身免疫疾病的MRL / MPJ小鼠表现出与SW相比,在暴露于SW时表现出性别相关的疾病发展加速。因此,Longterm暴露于昼夜相移,MIMIC SW在各种疾病模型中降低了健康或寿命。我们的方法提供了一种简单的方法来评估慢性昼夜破坏在风险基因型中疾病发育的影响。

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