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生物钟调控肝脏再生与衰老的研究进展

Research advances in biological clock-mediated regulation of liver regeneration and aging

  • 摘要: 作为进化过程中形成的内源性调控机制,生物钟依托核心时钟基因构成的转录-翻译反馈环路,维持并协调睡眠节律、进食行为、激素分泌及体温稳态等生理功能与行为模式。肝脏作为代谢核心器官,其代谢、解毒、再生与衰老等过程均受到生物钟的精确调控。生物钟通过调控关键细胞周期调节因子和肝脏再生相关信号通路的基因表达,并协调再生进程中的生物合成与代谢重编程过程, 从而精准调控肝细胞的增殖节律与肝脏组织的修复过程。此外,生物钟不仅直接调控肝脏的衰老进程,还通过介导多器官间对话,系统性地影响全身性衰老及其相关疾病发生风险,这凸显了其在维持机体整体稳态中的核心作用。本综述系统总结近年来肝脏自主生物钟的生理功能与调控机制相关研究进展,重点阐述生物钟在肝脏组织再生与衰老进程中的双重调控作用,为基于生物钟的肝脏疾病靶向治疗和健康管理提供了理论基础与新视角。

     

    Abstract: As an endogenous regulatory mechanism formed during evolution, the biological clock maintains and coordinates physiological functions and behavioral patterns such as sleep-wake rhythms, feeding behavior, hormone secretion, and body temperature homeostasis through transcription-translation feedback loops composed of core clock genes. The liver, as the central metabolic organ, is subjected to the precise regulation of the circadian clock in processes such as metabolism, detoxification, regeneration and aging. The biological clock exerts precise control over the proliferation rhythm of hepatocytes and the repair process of liver tissue by regulating the gene expression of key cell cycle regulators and liver regeneration-related signaling pathways and coordinating biosynthesis and metabolic reprogramming. Moreover, the biological clock not only directly regulates the aging process of the liver but also systemically affects systemic aging and the risk of associated diseases by mediating inter-organ crosstalk, highlighting its central role in maintaining overall physiological homeostasis. This review systematically summarizes the recent research advances in the physiological functions and regulatory mechanisms of the liver intrinsic biological clock, focuses on the dual regulatory roles of the biological clock in liver regeneration and aging. It provides a theoretical foundation and novel perspectives for the development of biological clock-based targeted therapies and health management strategies for liver diseases.

     

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