The circadian clock at the intersection of metabolism and aging – emerging roles of metabolites

Yue Dong; Sin Man Lam; Yan Li; Min-Dian Li; Guanghou Shui

doi:10.1016/j.jgg.2025.04.014

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The circadian clock at the intersection of metabolism and aging – emerging roles of metabolites

doi: 10.1016/j.jgg.2025.04.014

a. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
b. University of the Chinese Academy of Sciences, Beijing 100049, China;
c. LipidALL Technologies Company Limited, Changzhou, Jiangsu 213022, China;
d. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing 100101, China;
e. Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, MOE Key Laboratory of Geriatric Cardiovascular and Cerebrovascular Disease, Southwest Hospital, Army Medical University, Chongqing 400038, China;
f. Guangzhou National Laboratory, Guangzhou, Guangdong 510005, China

Funds:

This work was supported by grants from the Chinese Academy of Sciences (XDB39050800), the Major Project of Guangzhou National Laboratory (GZNL2024A03013), and the National Natural Science Foundation of China (92357308 and 32321004).

Received Date: 2025-04-06
Accepted Date: 2025-04-24
Rev Recd Date: 2025-04-24

Available Online: 2025-07-11

Abstract

Abstract

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.
- Metabolites,
- Circadian clock,
- Aging,
- Pacemakers,
- Metabolic diseases