1Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Neuroscientist. 2014 Feb;20(1):44-55. doi: 10.1177/1073858413498936. Epub 2013 Aug 7.
More than half of the elderly in today's society suffer from sleep disorders with detrimental effects on brain function, behavior, and social life. A major contribution to the regulation of sleep stems from the circadian system. The central circadian clock located in the suprachiasmatic nucleus of the hypothalamus is like other brain regions subject to age-associated changes. Age affects different levels of the clock machinery from molecular rhythms, intracellular messenger, and membrane properties to neuronal network synchronization. While some of the age-sensitive components of the circadian clock, like ion channels and neurotransmitters, have been described, little is known about the underlying mechanisms. In any case, the result is a reduction in the amplitude of the circadian timing signal produced by the suprachiasmatic nucleus, a weakening in the control of peripheral oscillators and a decrease in amplitude and precision of daily rhythms in physiology and behavior. The distortion in temporal organization is thought to be related to a number of serious health problems and promote neurodegeneration. Understanding the mechanisms underlying age-related deficits in circadian clock function will therefore not only benefit rhythm disorders but also alleviate age-associated diseases aggravated by clock dysfunction.
当今社会，超过一半的老年人患有睡眠障碍，这对大脑功能、行为和社交生活都有不利影响。调节睡眠的一个主要因素来自于生物钟系统。位于下丘脑视交叉上核的中央生物钟就像其他大脑区域一样，会受到与年龄相关的变化的影响。年龄会影响生物钟机制的不同层面，从分子节律、细胞内信使和膜特性到神经元网络同步。虽然已经描述了一些生物钟的年龄敏感成分，如离子通道和神经递质，但对于潜在机制知之甚少。无论如何，结果是视交叉上核产生的昼夜节律计时信号的幅度降低，外周振荡器的控制减弱，以及生理和行为的日常节律幅度和精度降低。时间组织的扭曲被认为与许多严重的健康问题有关，并促进神经退行性变。因此，了解生物钟功能与年龄相关的缺陷的机制不仅将有益于节律障碍，而且还将缓解因时钟功能障碍而加重的与年龄相关的疾病。
