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It all started with the discovery in the fruit fly (Drosophila melanogaster) of a gene (period) that encodes a protein (PER) that accumulates during the night and degrades during the day.

It continued with the discovery of a second, timeless clock gene, and culminated with the complete description of the molecular mechanisms that control circadian rhythms that allow living beings to adapt to their environment.

This is the so-called internal clock with which plants and animals – including humans – synchronize their biological rhythm with the rotation of the Earth. The scientists who unraveled this circadian machinery Michael Rosbash, Jeffrey Hall, and Michael Young were awarded the Nobel Prize in Medicine in 2017.

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Bless you.

How Time Adjustment Affects Us: One Hour on the Wristwatch, Several Weeks on the Sundial

  • Written by: GRACIA PABLOS (Text and graphics)

How Time Adjustment Affects Us: One Hour on the Wristwatch, Several Weeks on the Sundial

Bless you.

The scientist who watches over your sleep: "To keep our circadian system on time, it is key to correctly expose ourselves to a cycle of light and dark"

  • Written by: CRISTINA G. LUCIO Madrid

The scientist who watches over your sleep: "To keep our circadian system on time, it is key to correctly expose ourselves to a cycle of light and dark"

The environment in which human beings live is undergoing profound transformations due to climate change. Rosbash, who has just visited Spain as part of the global Nobel Prize Inspiration Initiative and with the help of the AstraZeneca Foundation, commented in an interview with Diario Médico that it is very possible that these changes will exert some influence. However, he points out, "circadian rhythms are quite invariant or insensitive to temperature; they are constituted in a different way."

Hence, "paradoxically, they could be the physiological piece least affected by climate change." Oscillations between light and dark do influence the internal clock, but it should be noted that light "is not going to change too much because of climate change".

The geneticist details the three findings that he found most surprising in his research on circadian mechanisms. "First of all, I was surprised that the genes and genetic underpinnings of the fruit fly are so well conserved in mammals, including humans." Another unexpected discovery was "the very large proportion of gene expression that is under circadian control."

Finally, he was shocked by the number of tissues it encompasses. "At first we thought it might be restricted to a very small fraction of cells and tissues in animals, but it's widespread." In short, these are very generalized mechanisms from a genetic and functional point of view that, moreover, are preserved throughout evolution.

Far Beyond the Brain and Sleep

When talking about the scope of circadian mechanisms, sleep and the brain are often cited as examples, but their physiological and anatomical scope is much greater, to the point that it can be said that it is global.

All Olympic records have been made in the late afternoon, because this is when peak physiological performance can take place

Michael Rosbash

"It includes many aspects of physiology, such as daily hormonal fluctuations of all kinds," Rosbash says. The Nobel laureate provides definitive proof of this ubiquitous influence: "All Olympic records have been made in the late afternoon, because that is when maximum physiological performance can take place." In short, practically everything you can imagine is under that physiological control, not to mention the libido.

The same can be said of tissues: liver, kidney, muscle, spleen, skin, pancreas, lung... "The little timekeeper is in absolutely every tissue," sums up the Nobel Prize winner in Medicine.

Circadian Mechanisms and Human Health

Once the molecular mechanisms that allow human beings to adapt to the Earth's rotation that marks the cycles of light that, in turn, determine the periods of sleep and wakefulness and other physiological functions have been revealed, it is worth asking how the malfunctioning of all this machinery affects human health. Rosbash acknowledges that, for the time being, it remains fairly uncharted territory, although he is convinced that there has to be a relationship.

Everything seems to indicate that those who have certain problems related to their circadian clock are destined to get sick, but it is not yet known for sure to what extent. "I'm sure there are people who have mutations that cause their clocks to go too fast or too slow," says the geneticist. But do these individuals live a shorter life span or do they get cancer more often? "I don't know," he replies. "It is known that there is a relationship with things like cancer, but it is not very direct and its true impact is unknown."

Challenges of genetics

Something similar is happening with genetic research, which has advanced spectacularly but still has many challenges pending. It is well known that the tentacles of genetics are very long because they affect all areas of life.

"Human genetics has undergone a revolution in the last 10 years that has impacted all areas," Rosbash said. Aberrant clock genes have been found to cause health problems, but "the extent to which they are impaired remains unknown, and in some cases it remains a mystery how a particular mutation is connected to a particular disease."

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