The internal clock as an important factor in translational research
The inner clock determines when humans and animals are awake and when they sleep. The discovery of the molecular tools and sensors of this so-called circadian rhythm was awarded the Nobel Prize for Physiology or Medicine in 2017. Gabriella Lundkvist from the Max Planck Institute for Biology of Ageing, together with a group of prominent researchers and two of these Nobel Laureates, has now published an article encouraging the research community to take greater account of these findings in their research.
Ageing, neurodegenerative diseases such as Alzheimer's and certain psychiatric diseases are characterized by disturbances in circadian rhythmicity. However, the importance of circadian biology is rarely considered when translating pre-clinical studies to the bedside. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This suggests that the biology of the target cell will determine whether an organ will respond to a drug at a specific time of the day. Circadian biology can thus become a critical factor for improving drug efficacy and diminishing drug toxicity.
Moreover, a large part of biological research is performed using mice, which are nocturnal animals. Their metabolic rate and behavioral activity are very low during daytime, whereas humans who are day-active have a very high metabolic rate and activity during the day. Translating nocturnal animal findings into humans may therefore cause significant difficulties and even scientific errors.
The researchers would like to make the biological community aware that it is now time that circadian factors become an integral part of basic biological as well as translational research.
Christopher R. Cederroth, Urs Albrecht, Joseph Bass, Steven A. Brown, Jonas Dyhrfjeld-Johnsen, Frederic Gachon, Carla B. Green, Michael H. Hastings, Charlotte Helfrich-Förster, John B. Hogenesch, Francis Lévi, Andrew Loudon, Gabriella B. Lundkvist, Johanna H. Meijer, Michael Rosbash, Joseph S. Takahashi, Michael Young, Barbara Canlon
Medicine in the Fourth Dimension
Cell Metabolism, August 2019