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.