Resetting of central and peripheral circadian oscillators in aged rats

Resetting of central and peripheral circadian oscillators in aged rats
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DOI:
10.1016/j.neurobiolaging.2006.10.018
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发表时间:
2008-03-01
影响因子:
4.2
通讯作者:
Block, Gene D.
Block, Gene D.
中科院分区:
医学2区
文献类型:
--
作者:
Davidson, Alec J.;Yamazaki, Shin;Block, Gene D.

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哺乳动物的昼夜节律系统受到衰老的影响。对视交叉上核(SCN)和其他昼夜节律振荡器的分析揭示了与年龄相关的变化,这些变化在SCN外组织中最为深刻。一些额外的scn振荡器似乎在体内停止振荡或显示改变的相位关系。为了确定昼夜节律振荡器的动态行为是否也受到衰老的影响,我们研究了外周和中心振荡器的周期转录节律在光照时间提前或延迟6小时时的重置行为。我们使用了一只带有荧光素酶报告基因的转基因大鼠来实时测量转录节律。虽然在2岁大鼠中,随着光周期的提前或延迟,SCN的相位重置几乎是正常的,但肝脏的再同步被严重破坏了。此外,与4-8个月大的对照组相比,老龄大鼠的弓形核和松果体表现出更快的重置。这些缺陷的后果尚不清楚,但可能会导致老年人的器官和脑部疾病,以及老年轮班工人常见的健康问题。(C) 2006爱思唯尔公司版权所有。
The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6 h advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year-old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus an pineal gland exhibited faster resetting in aged rats relative to 4-8-month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers. (C) 2006 Elsevier Inc. All rights reserved.