The circadian rhythm controls telomeres and telomerase activity

• Telomerase and TERT mRNA expressions exhibit endogenous circadian rhythm.
• Human and mouse TERT mRNA expression are under the control of CLOCK–BMAL1 heterodimers.
• CLOCK deficient mice have shortened telomere length and abnormal oscillations of telomerase activity and TERT mRNA.
• Emergency physicians working in shifts lose the circadian rhythms of telomerase activity.

Circadian clocks are fundamental machinery in organisms ranging from archaea to humans. Disruption of the circadian system is associated with premature aging in mice, but the molecular basis underlying this phenomenon is still unclear. In this study, we found that telomerase activity exhibits endogenous circadian rhythmicity in humans and mice. Human and mouse TERT mRNA expression oscillates with circadian rhythms and are under the control of CLOCK–BMAL1 heterodimers. CLOCK deficiency in mice causes loss of rhythmic telomerase activities, TERT mRNA oscillation, and shortened telomere length. Physicians with regular work schedules have circadian oscillation of telomerase activity while emergency physicians working in shifts lose the circadian rhythms of telomerase activity. These findings identify the circadian rhythm as a mechanism underlying telomere and telomerase activity control that serve as interconnections between circadian systems and aging.