Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α

Area of Science:

• Physiology
• Chronobiology
• Molecular Biology

Background:

• Mammalian circadian rhythms are regulated by a central brain clock and peripheral oscillators.
• Systemic cues like feeding and temperature cycles maintain clock synchrony.
• The role of oxygen as a circadian resetting cue remains largely unexplored.

Purpose of the Study:

• To investigate the role of oxygen as a resetting cue for circadian clocks.
• To determine the molecular mechanisms underlying oxygen's effect on circadian rhythms.
• To evaluate the potential of oxygen modulation for treating circadian rhythm disorders like jet lag.

Main Methods:

• Continuous measurement of oxygen levels in living animals to detect daily rhythms.
• Synchronization of cellular clocks using physiological oxygen cycles.
• Analysis of clock gene expression in response to oxygen level changes.
• Jet lag protocol in wild-type and HIF1α-deficient mice to assess adaptation.

Main Results:

• Daily rhythms in tissue oxygenation were detected in living animals.
• Physiological oxygen cycles were sufficient to synchronize cellular clocks in a HIF1α-dependent manner.
• Several clock genes exhibited responses to oxygen level variations mediated by HIF1α.
• Moderate oxygen reduction accelerated jet lag adaptation in wild-type mice but not in HIF1α-deficient mice.

Conclusions:

• Oxygen acts as a resetting cue for circadian clocks through HIF1α activation.
• Oxygen level modulation represents a potential therapeutic strategy for managing jet lag and other circadian rhythm disruptions.