Low temperature abolishes human cellular circadian rhythm through Hopf bifurcation

Circadian clocks orchestrate behavior, physiology, and metabolism in harmony with the Earth's 24-h cycle. Low temperatures are known to disrupt circadian clocks in plants and poikilotherms; however, their effects on human circadian rhythms remain poorly understood. Here, we demonstrate that cold exposure abolishes the circadian rhythm in cultured human cells through diminishing the oscillation amplitude, which was restored upon rewarming. In addition, the oscillation amplitude of the 24-h temperature cycles was enhanced through resonance, reflecting the intrinsic frequency of the circadian clock. From a theoretical perspective, these dynamics correspond to Hopf bifurcation, which is confirmed by a mathematical model for the mammalian circadian clock. In contrast, the circadian amplitude of human hair follicle cells was not significantly sensitive to temperature changes. These observations suggest a potential evolutionary advantage of maintaining Hopf bifurcation despite robust homeostasis.