Circadian Rhythm – A Prized Idea

For many years people have tossed out the phrase “circadian rhythm’ with little regard for it’s true significance to life.

That little phrase has received enormous attention when three scientists from the United States were awarded the Nobel Prize in Medicine for discovering genes that regulate the body clock.

What is a circadian rhythm?

A circadian rhythm is a roughly 24-hour cycle in the physiological processes of living beings, including plants, animals, fungi and cyanobacteria. In a strict sense, circadian rhythms are internally generated, although they can be modulated by external cues such as sunlight and temperature.

Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine on Monday for discoveries about the molecular mechanisms controlling the body’s circadian rhythm.

The three scientists used fruit flies to isolate a gene that controls the rhythm of a living organism’s daily life. Dr. Hall, Dr. Rosbash and Dr. Young were “able to peek inside our biological clock,” helping “explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions,” the Nobel Prize committee said.

By examining the internal workings of fruit flies, the investigators helped determine that the gene they were analyzing encoded a protein that accumulated in cells at night, and then degraded during the day.

Over decades of research, these scientists identified the mechanisms governing the clockwork inside the cell, shedding light on the biology of humans and other multicellular organisms whose biological clocks function on the same principles.

With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day. The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism. Our wellbeing is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience “jet lag”. There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner timekeeper is associated with increased risk for various diseases.

The researchers studied fruit flies in which a gene called period seemed to control circadian rhythm; when it was mutated, the insects lost that rhythm.

But what was period, and how did it work? The questions were relevant not just to flies: All organisms, including humans, operate on 24-hour rhythms that control not only sleep and wakefulness but also physiology generally, including blood pressure and heart rate, alertness, body temperature and reaction time.

In 1984, the scientists isolated the period gene and discovered that cells use it to make a protein that builds up at night, during sleep. In daytime, the protein degrades in accordance with the insects’ sleep-wake cycle.  The researchers believed that this protein, which they called PER, somehow blocked the period gene during the day. As PER was broken down in daytime, the gene regained its function and worked again the next night, directing the synthesis of PER.

The entire system turned out to involve several other proteins needed to control the accumulation of PER. These include one that attaches to PER, helping to block the period gene, and another that slows the buildup of the protein.

Continuing to investigate this biological system over the years, the scientists went on to discover still other components, notably one that allows light to influence the 24-hour rhythm.

Their work was pivotal, the Nobel committee said, because the misalignment between a person’s lifestyle and the rhythm dictated by an inner timekeeper — jet lag after a trans-Atlantic flight, for example — could affect well-being and over time could contribute to the risks for various diseases.

It is great to see a reward for something that doesn’t have a connection to large pharmaceutical interests.

As one of the scientists said, “Today is a great day for the fruit fly!”

I am hopeful that this research will continue to help people with their sleep patterns, hormone imbalance and so many other variables that can be affected by daylight and temperature.

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