Martínez-García Juan Jose, Rainteau Dominique, Humbert Lydie, Lamaziere Antonin, Lesnik Philippe, Chamaillard Mathias
Laboratory of Cell Physiology, INSERM U1003, University of Lille, F-59019 Lille, France.
Centre de Recherche Saint-Antoine, CRSA, AP-HP.SU, Hôpital Saint Antoine, Département de Métabobolomique Clinique, Sorbonne Université, INSERM, F-75012 Paris, France.
Metabolites. 2022 Apr 26;12(5):390. doi: 10.3390/metabo12050390.
The behavior and physiology of most organisms are temporally coordinated and aligned with geophysical time by a complex interplay between the master and peripheral clocks. Disruption of such rhythmic physiological activities that are hierarchically organized has been linked to a greater risk of developing diseases ranging from cancer to metabolic syndrome. Herein, we summarize the molecular clockwork that is employed by intestinal epithelial cells to anticipate environmental changes such as rhythmic food intake and potentially dangerous environmental stress. We also discuss recent discoveries contributing to our understanding of how a proper rhythm of intestinal stem cells may achieve coherence for the maintenance of tissue integrity. Emerging evidence indicates that the circadian oscillations in the composition of the microbiota may operate as an important metronome for the proper preservation of intestinal physiology and more. Furthermore, in this review, we outline how epigenetic clocks that are based on DNA methylation levels may extensively rewire the clock-controlled functions of the intestinal epithelium that are believed to become arrhythmic during aging.
大多数生物体的行为和生理活动在时间上是协调一致的，并通过主时钟和外周时钟之间的复杂相互作用与地球物理时间保持同步。这种分层组织的节律性生理活动的破坏与从癌症到代谢综合征等多种疾病的发生风险增加有关。在此，我们总结了肠道上皮细胞用来预测环境变化（如有节律的食物摄入和潜在危险的环境压力）的分子时钟机制。我们还讨论了最近的发现，这些发现有助于我们理解肠道干细胞的适当节律如何实现维持组织完整性的协调性。新出现的证据表明，微生物群组成的昼夜节律振荡可能作为一个重要的节拍器，以适当维持肠道生理功能等。此外，在本综述中，我们概述了基于DNA甲基化水平的表观遗传时钟如何广泛地重新连接肠道上皮细胞的时钟控制功能，这些功能在衰老过程中被认为会变得无节律。
