《生命科学》 2026, 38(6): 1095-1113
昼夜节律在衰老及相关疾病中的作用机制研究进展
摘 要：
昼夜节律作为内源性计时系统，通过多层级调控网络协调机体生理、代谢与行为，对维持健康稳态具有关键作用。衰老过程常伴随昼夜节律紊乱，表现为视交叉上核功能失调、节律振幅减弱及外周时钟失同步等特征；同时，节律紊乱也可加速衰老进程，并促进神经退行性疾病、心血管与代谢性疾病、呼吸系统疾病等多种衰老相关疾病的发展。本文综述昼夜节律的分子调控机制、在衰老过程中的变化特征及其与相关疾病的作用联系，旨在为揭示生物钟在衰老及相关疾病中的调控规律、开发基于节律调节的干预策略提供理论依据。
通讯作者：陈一凡 , Email:yifanchen@sjtu.edu.cn 卜 军 , Email:pujun310@hotmail.com
Abstract:
Circadian rhythms function as the body′s endogenous timing system, coordinating physiology, metabolism, and behavior through a multi-level regulatory network to maintain health and homeostasis. Aging is typically accompanied by progressive deterioration of this circadian system, characterized by functional decline of the suprachiasmatic nucleus (SCN) and disrupted clock synchrony across tissues. A key insight is the bidirectional nature of this relationship—circadian disruption not only results from aging but also actively accelerates it while promoting the development of multiple age-related diseases, including neurodegenerative, cardiovascular, metabolic, and respiratory disorders. This review examines the molecular regulatory mechanisms of circadian rhythms, their characteristic alterations during aging, and their functional links to age-related pathologies. The circadian system operates hierarchically: the SCN serves as the master pacemaker, integrating environmental light signals and synchronizing peripheral oscillators primarily through neural and humoral pathways. At the cellular level, oscillations arise from transcriptional/translational feedback loops (TTFLs) involving core clock genes (BMAL1, CLOCK, PER, CRY) and auxiliary loops (REV-ERBs, RORs), with post-translational modifications ensuring precise 24-hour timing. Aging significantly compromises this architecture: the SCN undergoes neuronal loss, reduced firing amplitude, impaired intercellular coupling, and diminished light sensitivity. These changes collectively weaken behavioral rhythms while disrupting signaling to peripheral tissues, with disruption of behavioral rhythms and autonomic function further exacerbating central-peripheral desynchronization. Circadian disruption accelerates aging through interconnected mechanisms, including hormonal imbalances, chronic inflammation, metabolic disturbances, and oxidative stress. These processes collectively drive cellular senescence and DNA damage, forming a vicious cycle that progressively erodes tissue homeostasis. Accumulating evidence links these mechanisms to major age-related diseases. In neurodegenerative disorders, clock dysfunction exacerbates protein aggregation, neuroinflammation, and impaired waste clearance. In cardiovascular and metabolic diseases, circadian misalignment disrupts blood pressure rhythms, platelet aggregation, ion channel expression, and hepatic metabolism. Respiratory conditions similarly exhibit circadian vulnerability due to clock-controlled inflammation and tissue remodeling. Understanding these interactions provides a rationale for chronotherapeutic interventions—including timed light exposure, consistent sleep-wake schedules, time-restricted eating, and optimized drug timing—which may mitigate agerelated decline. Future research should elucidate the spatiotemporal progression of clock disruption during aging and its interplay with key aging pathways, while leveraging artificial intelligence and wearable technologies to advance personalized chronotherapy and extend healthspan.
Communication Author：CHEN Yi-Fan , Email:yifanchen@sjtu.edu.cn PU Jun , Email:pujun310@hotmail.com
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