Changing Biological Clocks

Kyungseok Jung | Assistant Editor of Natural Sciences

Whether it be working late night shifts, travelling across the world, or re-training ourselves to wake up before 2 PM, we have all tried tirelessly to shift our sleep schedules.

Circadian clocks are present in every cell of our body and regulate physiological processes in response to changes in the environment. Not surprisingly, trying to adjust sleep schedules can take a major toll on our bodies, as the circadian system keeps our cells in sync with our “master” internal clock1.

In a recent study by Adamovich et al.2 at the Weizmann Institute of Science, the role of oxygen was investigated as a “resetting cue” for circadian clocks. The researchers discovered that decreasing oxygen levels for short periods of time expedites jet-lag recovery in mice.

sleep In previous research, scientists have identified feeding-fasting cycles and temperature cycles as other cues that affect the circadian rhythm. However, this research firmly establishes that oxygen levels are also a major factor in modulating circadian rhythm patterns. This makes sense, as both dietary and temperature regulations are processes that affect oxygen consumption.

To test whether fluctuations in oxygen levels correlated with changes in circadian cycles, researchers monitored the temporal blood oxygen level and oxygen consumption rate in mice. Their analyses revealed that both of these variables underwent cyclic daily oscillations, and oxygen consumption rate was the highest during the night when mice were active.

Similar results were obtained in experiments where cultured cells were exposed to three consecutive 12 hour cycles of oxygen, shifting between 5% and 8%. These cells, which were exposed to conditions that mimicked physiological rhythms of oxygen consumption, exhibited rhythmic expression of clock genes. However, control cells constantly exposed to 8% oxygen did not exhibit such variable expression, indicating that the cultured cells exposed to fluctuating levels of oxygen had synchronized to a new rhythm.

Researchers excitedly wondered what had incited the observed changes. The culprit turned out to be HIF1α, a transcription factor, or a protein involved in transcribing DNA to RNA. Having examined the role of HIF1α in resetting the molecular clock in their experiments, the researchers employed siRNA molecules to specifically knock down HIF1α without affecting other genes. They failed to detect rhythmic expression of clock genes in such HIF1α-deficient cells, suggesting that HIF1α serves as a potential link between oxygen and the circadian clock through gene regulation.

Structure-of-HIF1a-Diagram-highlighting-the-structural-domains-of-HIF1a

HIF1α, a transcription factor, serves as a potential link between oxygen and the circadian clock through gene regulation.

Once the lights were turned off, mice exhibited robust-rest activity cycles every 24 hours. In a later experiment, researchers shifted the lighting schedule by 6 hours to confuse the mice’s biological clocks and mimic jet-lag. Normally, mice breathe air with 21% oxygen. Remarkably, researchers found that exposing mice to 16% oxygen for 12 hours prior, as well as 14% oxygen following the change, accelerates the adaptation of mice to new lighting schedules. The same results could not be replicated in HIF1α-deficient mice, indicating the importance of HIF1α and oxygen levels to circadian rhythm regulation.

If oxygen truly affects our circadian rhythms, adjusting oxygen levels in response to jet-lag might prove to be effective. Ironically, the researchers mention that the aviation industry is working to increase cabin oxygen levels to 21% from the current 16%. Nonetheless, a better understanding of this phenomenon will allow us to implement changes and develop technologies that can make the destabilizing effects of sustained jet-lag a thing of the past. Until then, try breathing a little less during your late night cram sessions to reduce tiredness – success is not guaranteed, but it’s worth a try anyway.

References

  1. Adamovich, Yaarit, Benjamin Ladeuix, Marina Golik, Maarten P. Koeners, and Gad Asher. “Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α.” Cell Metabolism, 2016. doi:10.1016/j.cmet.2016.09.014.
  2. Ortmann, B., Druker, J., & Rocha, S. (2014). Cell cycle progression in response to oxygen levels. Cellular and Molecular Life Sciences, 71(18), 3569-3582. doi:10.1007/s00018-014-1645-9
  3. Sleep Drive and Your Body Clock. (n.d.). Retrieved November 02, 2016, from https://sleepfoundation.org/sleep-topics/sleep-drive-and-your-body-clock
  4. Whelan, C. (2015, September 16). Is Yawning Actually Contagious? Retrieved November 02, 2016, from https://sites.psu.edu/siowfa15/2015/09/16/is-yawning-actually-contagious/

Featured photo from tommyspero.com

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