Dong Yue, Lam Sin Man, Li Yan, Li Min-Dian, Shui Guanghou
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; LipidALL Technologies Company Limited, Changzhou, Jiangsu 213022, China.
J Genet Genomics. 2025 Apr 29. doi: 10.1016/j.jgg.2025.04.014.
The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops, which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues. While circadian clocks regulate metabolic processes and related physiology, emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined. In this review, we highlight the concept of metabolites, including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake, as time cues that drive changes in circadian rhythms, which in turn influence metabolism and aging. Furthermore, we discuss the roles of functional metabolites as circadian cues, paving a new direction on potential intervention targets of circadian disruption, pathological aging, as well as metabolic diseases that are clinically important.
昼夜节律时钟是一个高度分层的内源性起搏器网络，主要通过转录和翻译反馈回路维持和引导振荡，从而调节细胞和组织内约24小时的内分泌和代谢节律周期。虽然昼夜节律时钟调节代谢过程及相关生理学，但新出现的证据表明，代谢和昼夜节律密切相关。在本综述中，我们强调了代谢物的概念，包括肠道微生物代谢和营养摄入产生的脂质和其他极性代谢物，它们作为时间线索驱动昼夜节律的变化，进而影响代谢和衰老。此外，我们还讨论了功能性代谢物作为昼夜节律线索的作用，为昼夜节律紊乱、病理性衰老以及具有临床重要性的代谢性疾病的潜在干预靶点开辟了新方向。
