The role of the multiplicity of circadian clocks in mammalian systems.

Circadian clocks regulate rhythmic biological processes in nearly every tissue, aligning physiology and behavior with the 24-h light-dark cycle. While the central circadian clock in the suprachiasmatic nucleus (SCN) has been extensively studied, emerging evidence indicates that virtually every cell in the body possesses its own locally autonomous circadian clock. This raises a fundamental question: why do multicellular organisms utilize multiple circadian clocks instead of a single master clock broadcasting time cues? Here, we examine how distributed local clocks differ from phase-resettable cycles and ensure robust temporal scheduling of physiological processes. We discuss how internal entrainment among local clocks governs self-sustained, yet flexible, circadian organization of tissue-specific responses to environmental changes. We also examine how the organization of clocks contributes to seasonal homeostasis, and the implications for disease when coordination among these clocks is disrupted.