"When the balance between clock proteins is upset, normal cellular function can be disrupted," said Sassone-Corsi, who also directs the Center for Epigenetics & Metabolism at UC Irvine.
In exploring how to regulate SIRT1 activity, Sassone-Corsi teamed with scientists from two research-and-development groups at GlaxoSmithKline one in the United Kingdom and the other (called Sirtris) in the U.S. to test proprietary small-molecule compounds that stimulate SIRT1.
In mouse studies, they were able to modulate the scale of circadian-driven gene function with the SIRT1-activating compounds, effectively governing the circadian cycle in a host of genes involved with the metabolic rate in cells. This research proves that small molecules can be used as a pharmacological strategy to control circadian disturbances and is a step toward the development of drugs that could target many conditions, including metabolic disorders, diabetes, cancer and aging.
Postdoctoral researchers Selma Masri and Kristin Eckel-Mahan, graduate student Vishal Patel and Chancellor's Professor Pierre Baldi of UC Irvine, along with Shahaf Peleg, Ignasi Forne, Andreas Ladurner and Axel Imhof of Germany's University of Munich, as well as Sassone-Corsi, contributed to the study titled "The Circadian acetylome reveals regulation of mitochondrial metabolic pathways." The National Institutes of Health, the National Science Foundation, INSERM and Sirtris provided support.
In addition to Sassone-Corsi, postdoctoral researcher Marina Bellet and laboratory assistant Marlene Cervantes of UC Irvine; Mohamed Boudjelal, Emma Watts, Danuta Mossakowska and Kenneth Edwards of GlaxoSmithKline; Giuseppe Astarita of Georgetown University; and Christine Loh, James Ellis and George Vlasuk of Sirtris contri
|Contact: Tom Vasich|
University of California - Irvine