Orozco-Solis R, Sassone-Corsi P
Center for Epigenetics and Metabolism, Unite 904 INSERM, Department of Biological Chemistry, University of California, Irvine, CA 92697, United States.
Center for Epigenetics and Metabolism, Unite 904 INSERM, Department of Biological Chemistry, University of California, Irvine, CA 92697, United States.
Neuroscience. 2014 Apr 4;264:76-87. doi: 10.1016/j.neuroscience.2014.01.043. Epub 2014 Jan 31.
Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape.
实验和流行病学证据显示，在过去50年里，工业化现代社会对人类社会习惯和生理机能产生了深远影响。这种生活方式的急剧变化被认为是包括肥胖、2型糖尿病、抑郁症等精神疾病、睡眠障碍以及某些类型癌症在内的现代疾病的主要原因之一。这些疾病与生物钟紊乱有关，生物钟是一种几乎存在于所有细胞和组织中的内在计时分子系统。生物钟通过控制大量参与细胞代谢的基因，是体内平衡调节的关键要素。重要的是，表观遗传调控与生物钟之间存在密切联系，并且可能对环境反应的可塑性有显著贡献。在这篇综述中，我们总结了一些实验和流行病学证据，展示了诸如压力、滥用药物和昼夜节律习惯变化等环境因素如何通过不同脑区相互作用来调节内源性生物钟。此外，我们指出脱乙酰酶沉默交配型信息调节2同源物1（SIRT1）作为环境在塑造昼夜节律表观遗传格局中的分子效应器的关键作用。
