Studies led by UC Irvine have uncovered an important cellular mechanism that your body clock, or circadian rhythms, uses to modify energy metabolism, as well as also discovering novel compounds that control this action. Not only does this mean great implications to your wellbeing if you have diabetes, but the findings also point to treatments for many disorders that are triggered by circadian rhythm dysfunction, and people with insomnia, obesity and cancer could also see their wellness improve.
The study leader, UC Irvine’s Paolo Sassone-Corsi, worked with international groups of scientists to produce their results, which are published in the early online edition of the Proceedings of the National Academy of Science. According to Sassone-Corsi, Donald Bren Professor of Biological Chemistry, ‘Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Disruption of these rhythms can profoundly influence human health.’ 15% of your genes are regulated by the day-night pattern of circadian rhythms, he added.
One study revealed that your biological clock controls the enzymes localized in your mitochondrion, which is the cellular structure in your body that is devoted to energy metabolism. Sassone-Corsi and his colleagues found that the means by which your biological clock achieves this is through the acetylation of proteins, which is a process that operates as a switch to turn genes on and off in your cells based upon their energy usage.
An enzyme protein called SIRT1, which senses energy levels in the cell, dictates some of the most important acetylation events in cells, as well as helping your body to resist oxidative and radiation-induced stress. SIRT1 has been linked to the inflammatory response, diabetes and aging, which is why Sassone-Corsi teamed with scientists from the United Kingdom and the United States to test proprietary small-molecule compounds that stimulate SIRT1.
During these studies, which were done in mice, the team managed to modulate the scale of circadian-driven gene function with the SIRT1-activating compounds, meaning that they were able to effectively govern the circadian cycle in many of the genes that are involved with the metabolic rate in cells. This proves that a pharmacological strategy, using small molecules, could control circadian disturbances, meaning new drugs that target a whole host of conditions, including metabolic disorders, diabetes, cancer and aging.
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