Department of Drug Sciences (Pharmacology Section), University of Pavia, V.le Taramelli 14, 27100, Pavia, Italy.
Department of Life and Environmental Sciences, Polytechnic University of Marche, via Brecce Bianche, 60131, Ancona, Italy.
Signal Transduct Target Ther. 2022 Feb 8;7(1):41. doi: 10.1038/s41392-022-00899-y.
The term "circadian rhythms" describes endogenous oscillations with ca. 24-h period associated with the earth's daily rotation and light/dark cycle. Such rhythms reflect the existence of an intrinsic circadian clock that temporally orchestrates physiological processes to adapt the internal environment with the external cues. At the molecular level, the circadian clock consists of multiple sets of transcription factors resulting in autoregulatory transcription-translation feedback loops. Notably, in addition to their primary role as generator of circadian rhythm, the biological clock plays a key role in controlling physiological functions of almost all tissues and organs. It regulates several intracellular signaling pathways, ranging from cell proliferation, DNA damage repair and response, angiogenesis, metabolic and redox homeostasis, to inflammatory and immune response. In this review, we summarize findings showing the crosstalk between the circadian molecular clock and some key intracellular pathways, describing a scenario wherein their reciprocal regulation impinges upon several aspects of mammalian physiology. Moreover, based on evidence indicating that circadian rhythms can be challenged by environmental factors, social behaviors, as well as pre-existing pathological conditions, we discuss implications of circadian misalignment in human pathologies, such as cancer and inflammatory diseases. Accordingly, disruption of circadian rhythm has been reported to affect several physiological processes that are relevant to human diseases. Expanding our understanding of this field represents an intriguing and transversal medicine challenge in order to establish a circadian precision medicine.
“昼夜节律”一词描述了与地球每日自转和明暗周期相关的约 24 小时周期的内源性波动。这种节律反映了内在生物钟的存在，它暂时协调生理过程，使内部环境适应外部线索。在分子水平上，生物钟由多组转录因子组成，导致自动调节的转录-翻译反馈环。值得注意的是，生物钟除了作为昼夜节律的主要生成器之外，还在控制几乎所有组织和器官的生理功能方面发挥着关键作用。它调节几种细胞内信号通路，从细胞增殖、DNA 损伤修复和反应、血管生成、代谢和氧化还原稳态到炎症和免疫反应。在这篇综述中，我们总结了表明昼夜分子钟与一些关键细胞内途径之间相互作用的发现，描述了它们相互调节影响哺乳动物生理学几个方面的情况。此外，基于昼夜节律可能受到环境因素、社会行为以及现有病理状况挑战的证据，我们讨论了昼夜节律失调在人类疾病（如癌症和炎症性疾病）中的意义。因此，据报道，昼夜节律的破坏会影响与人类疾病相关的几种生理过程。扩大我们对这一领域的理解是一个有趣的、跨学科的医学挑战，以便建立精准的生物钟医学。
