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Professors weigh in on Nobel Prize-winning circadian rhythm research

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By isolating genes in fruit flies, three scientists were able to better study daily biological rhythms in organisms.

Three scientists received the Nobel Prize in Physiology or Medicine this month for their breakthrough in circadian rhythm research, which helps determine human sleep patterns, metabolism and hormone levels.

The scientists — Jeffrey Hall, Michael Rosbash and Michael Young — isolated a gene in fruit flies that controls daily biological rhythms in organisms.

To learn more about the importance of this breakthrough, The Daily Orange spoke with Margaret Voss, a Syracuse University nutritional studies and biochemistry professor; Vincent Cassone, a chronobiology and neuroscience professor at the University of Kentucky, via email; and Paul Bartell, a professor of avian biology at Pennsylvania State University.

The Daily Orange: Why is this discovery considered so important to human health and well-being?

Vincent Cassone: There has been a long-standing debate concerning whether genetics or rearing affects behavior. This nature versus nurture controversy was, in some sense, put to rest as it pertains to circadian rhythms and sleep, by the pioneering work of the Nobel Prize-winning scientists. They were able to isolate and characterize the period gene and then other genes associated with biological clock function.



Their work showed that in Drosophila fruit flies, the transcription and translation of these and other “clock genes” govern the 24-hour cycle of sleep and wakefulness. What was really surprising was that these genes in flies were also produced in other kinds of animals, including humans.

Mutations in these genes in humans resulted in the same kind of sleep-wake problems that mutant flies (experience).

Later, people found that dysfunctional expression of clock genes affects cancer, cardiovascular disease, obesity and gastrointestinal problems.

The D.O.: How do circadian rhythms work in our body?

Margaret Voss: Circadian rhythms divide our behavior into active and inactive periods, and human circadian rhythms are set up so that our active periods are … when it is light out. It allows some tissues to be more active during the dark phase and other tissues to be active during our light phase.

The D.O.: What types of things can throw off our circadian rhythms?

M.V.: We start to see that things like eating late and looking at our phones late at night are altering our inner clock. You also alter your circadian clock instantly by getting on a plane to the other side of the world.

It takes several days for the clock to reset, and it’s not just the sleep cycle that is affected by jet lag. The digestive system, brain function and cell division and growth are also disrupted.

V.C.: Mutation of the genes themselves can throw this off. There are people who have sleep disorders due to mutations in these clock genes passed down from parents. Also, many drugs and hormones affect the mechanisms associated with biological rhythms. Perhaps the most common way the clock mechanism is altered is through … light.

The D.O.: What are some effects we could see if there is chronic misalignment between our lifestyles and our circadian rhythms?

M.V.: Take the example of ingesting a Taco Bell burrito at 2 a.m. during the dark phase. The body uses some of that for energy.

However, it all depends on the person — if you’re not at an energy deficit, and you’ve been eating pretty regularly, the body will then store that as fat.

People that have to regularly eat late at night and are constantly changing their circadian patterns because of their schedules — such as first responders or people that have been constantly traveling — are at higher risk for cardiovascular disease and metabolic syndrome.

Paul Bartell: Pretty much any key pathway within the body is going to be finely tuned within that circadian clock.

For college students particularly, pulling all-nighters is a less effective way of studying because you are disrupting your clock and essentially not getting enough sleep to store those memories.

The D.O.: What are some implications this discovery could have on the future of medicine, in terms of human health and well-being?

P.B.: Jet lag used to be the only reason this type of research was given much attention. It is a consequence of your internal clock being out of synchrony with your external environment, and people can see immediate effects from that.

Now, there is that recognition of the importance of circadian rhythms outside of the more apparent effects of jet lag.

For example, particularly with cancer research, studies have shown that the time of day you (take) medicine will make it more or less effective. Certain chemotherapy drugs are more effective at 3 a.m.

The discovery of this … led to the discovery about how other genes can be turned on and off, and it impacts every aspect of our being.





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