Froy Oren, Miskin Ruth
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel.
Prog Neurobiol. 2007 Jun;82(3):142-50. doi: 10.1016/j.pneurobio.2007.03.002. Epub 2007 Mar 31.
The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain regulates circadian rhythms in mammals. Similar circadian oscillators have been found in peripheral tissues, such as the liver, intestine and retina. Life span has been previously linked independently to both circadian rhythms and caloric restriction (CR). The mechanisms by which CR attenuates ageing and extends life span are virtually unknown. It has recently been found that the alphaMUPA mice, transgenic mice that exhibit spontaneously reduced eating and live longer compared to their FVB/N wild-type control mice, show high amplitude, appropriately reset circadian rhythms. These pronounced rhythms were found both in clock gene expression in the liver and clock-controlled output systems, such as feeding time and body temperature. Furthermore, it was previously shown that CR could reset the central biological clock in the SCN. As the circadian clock in the SCN controls many physiological and biochemical systems, we suggest that appropriately reset peripheral rhythms could constitute an important mediator of longevity in calorically restricted animals. Thus, we suggest that three parameters, i.e., caloric restriction, circadian rhythms and life span, are interconnected. This surmise is novel, and we provide evidence to support it. Furthermore, we discuss other feeding regimens and their effects on circadian rhythms and/or life span.
位于大脑下丘脑前部视交叉上核（SCN）的主时钟调节哺乳动物的昼夜节律。在肝脏、肠道和视网膜等外周组织中也发现了类似的昼夜节律振荡器。此前，寿命已分别独立地与昼夜节律和热量限制（CR）相关联。CR减缓衰老并延长寿命的机制几乎尚不清楚。最近发现，αMUPA小鼠，即与它们的FVB/N野生型对照小鼠相比表现出自发性进食减少且寿命更长的转基因小鼠，呈现出高振幅、适当重置的昼夜节律。在肝脏中的时钟基因表达以及诸如进食时间和体温等时钟控制的输出系统中都发现了这些明显的节律。此外，先前的研究表明CR可以重置SCN中的中央生物钟。由于SCN中的昼夜节律时钟控制着许多生理和生化系统，我们认为适当重置外周节律可能是热量限制动物长寿的一个重要调节因素。因此，我们认为热量限制、昼夜节律和寿命这三个参数是相互关联的。这一推测是新颖的，我们提供了证据来支持它。此外，我们还讨论了其他喂养方案及其对昼夜节律和/或寿命的影响。
