Evolving perspectives on the molecular and neural foundations of mammalian circadian rhythms

Circadian regulation is multilayered and hierarchical, enabling organisms to anticipate and adapt to daily environmental changes driven by the Earth's rotation. The classical transcriptional-translational feedback loop (TTFL) remains a foundational model, although recent studies have refined its mechanisms and exposed limitations. The discovery of RUVBL2 - an ancient core clock component conserved across eukaryotes - emphasizes the potential universality of fundamental timekeeping processes. In mammals, intercellular coupling enables the generation of precise and robust circadian rhythms in both metabolic and electrical activity within the central pacemaker, the suprachiasmatic nucleus (SCN). The SCN receives external cues and coordinates systemic physiology to adjust to daily environmental changes. This review provides an updated perspective on mechanisms underlying the generation of mammalian circadian rhythms from molecular to neural and circuit levels.