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Credit: https://www.rug.nl/sciencelinx/nieuws/2021/05/resetting-the-biological-clock-by-flipping-a-switch

A light-activated compound could be the key to resetting your biological clock

June 16, 2021

A joint scientific venture has created a compound that could slow down the cycle of the circadian clock, thereby preventing disease.
The circadian clock is a 24-hour biological cycle that developed in our cells as a result of evolving with the concept of day and night.
By introducing a varying light source, the circadian clock could be activated and deactivated to maintain optimal health.

Life on earth is truly unique in that it has evolved on a cycle of hot and cold—light and dark. In fact, did you know that the cells in our body adhere to a 24-hour biological cycle known as the circadian clock? What’s even more interesting is that once you disrupt this cycle—for example, working late at night without having sufficient sleep—it could result in disease. While the study of the circadian clock is still relatively new, scientists have discovered that the clock can be disrupted selectively in tissues and organs. According to Dr. Wiktor Szymanski—Professor of Radiological Chemistry at the University Medical Center, Groningen, the circadian clock in our bodies is controlled by a centered regulator in the suprachiasmatic nucleus—a region situated directly above the optic nerve in the brain. However, it’s important to note that each body cell has its own circadian clock. These clocks are characterized as oscillations during the production and breakdown of certain proteins in the cells. Recently, a study was conducted by Japanese and Dutch scientists to create a compound that could potentially resolve issues with circadian clocks in cells by introducing a compound that could elongate the 24-hour cycle—and then deactivate it using light. They demonstrated that it was possible to alter the 24-hour cycle in tissues and cells by lengthening it to a 28-hour cycle through the activation of this compound. But once the compound was deactivated, the tissues and cells reverted back to their regular cycle. The scientists, therefore, believe that this compound could prove useful in investigating and potentially discovering the cure to treat certain diseases that are caused by the disruption of the circadian clock. According to the first author of the study, Susan Kolarski—who is a Ph.D. student from the team guided by Ben Feringa, a professor of Organic Chemistry—it has become increasingly clear that disruption of the circadian clock in tissues and cells could be one of the leading factors of disease. One example of circadian clock disruption is when you experience jet lag—which is essentially a feeling of sickness caused by traveling from one time zone to another. Presently, scientists know very little about how our cells naturally coordinate these oscillations; as well as the overall effects that they have on the body. And so, the most ideal way to study these effects is by introducing a drug that disrupts the clocks but can be activated locally. Initially, Dr. Feringa and Dr. Szymanski had been working towards creating several compounds—such as anticancer drugs and antibiotics—that could be activated on and off through the use of light. But prior to Dr. Feringa and Dr. Szymanski’s work, circadian biologist Tsuyoshi Hirota—an associate professor at the Institute of Transformative Bio-Molecules at Nagoya University in Japan—created a kinase inhibitor known as longdaysin—which was observed to slow down the circadian clock up to a cycle that lasts about 48 hours. Kolarski borrowed longdaysin and fitted it with a light switch; giving him the ability to deactivate or activate the compound with green and violet light respectively. Despite taking several years develop, the end results were worth the wait. With the help of Japanese colleagues from the Nagoya University, scientists from the University of Groningen were able to demonstrate how the cycle of cultured cells was increased from 24 to 28 hours by treating them with the longdaysin derivative. Using green light, the scientists were able to deactivate the cells back to a 24-hour cycle and followed-up reactivation with a violet light that returned the cells back to a 28-hour cycle. Moreover, the scientists also altered the phase of the cycles in these cultured cells. They performed a three-day activation using the longdaysin derivative, then followed by deactivation. The end result was that the cells experienced a disruption in their 24-hour cycle by up to six hours. It was as if these particular cells were synchronized in a different time zone! That being said, the scientists are optimistic that a light-activated drug such as longdaysin could be put to good use against serious conditions. “We can actually reach quite a few organs with light, for example with an endoscope. The gastrointestinal tract and the respiratory system are easily reached, while other tissues may require small incisions to insert optic fibers,” says Szymanski. Advanced emerging alternatives have been created to generate light within tissues and organs through effects such as sonoluminescence and bioluminescence. Unfortunately, the intensity of these light sources is still way below that required to trigger a switch. Nevertheless, scientists like Feringa are confident that they will have increased the sensitivity in the next few years.

References: https://www.rug.nl/sciencelinx/nieuws/2021/05/resetting-the-biological-clock-by-flipping-a-switch

A light-activated compound could be the key to resetting your biological clock

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