Kolker Daniel E, Fukuyama Hiroo, Huang David S, Takahashi Joseph S, Horton Teresa H, Turek Fred W
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
J Biol Rhythms. 2003 Apr;18(2):159-69. doi: 10.1177/0748730403251802.
Aging alters numerous aspects of circadian biology, including the amplitude of rhythms generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, the site of the central circadian pacemaker in mammals, and the response of the pacemaker to environmental stimuli such as light. Although previous studies have described molecular correlates of these behavioral changes, to date only 1 study in rats has attempted to determine if there are age-related changes in the expression of genes that comprise the circadian clock itself. We used in situ hybridization to examine the effects of age on the circadian pattern of expression of a subset of the genes that comprise the molecular machinery of the circadian clock in golden hamsters. Here we report that age alters the 24-h expression profile of Clock and its binding partner Bmal1 in the hamster SCN. There is no effect of age on the 24-h profile of either Per1 or Per2 when hamsters are housed in constant darkness. We also found that light pulses, which induce smaller phase shifts in old animals than in young, lead to decreased induction of Per1, but not of Per2, in the SCN of old hamsters.
衰老会改变昼夜节律生物学的诸多方面,包括下丘脑视交叉上核(SCN)产生的节律幅度,SCN是哺乳动物中央昼夜节律起搏器所在位置,以及该起搏器对诸如光等环境刺激的反应。尽管先前的研究已经描述了这些行为变化的分子关联,但迄今为止,在大鼠中仅有一项研究试图确定构成昼夜节律时钟本身的基因表达是否存在与年龄相关的变化。我们使用原位杂交技术来研究年龄对金黄仓鼠中构成昼夜节律时钟分子机制的一部分基因的昼夜表达模式的影响。在此我们报告,年龄会改变仓鼠SCN中Clock及其结合伴侣Bmal1的24小时表达谱。当仓鼠饲养在持续黑暗环境中时,年龄对Per1或Per2的24小时表达谱均无影响。我们还发现,光脉冲在老年动物中诱导的相位偏移比在幼年动物中更小,这导致老年仓鼠SCN中Per1的诱导减少,但Per2没有减少。