Insomnia often is our body clock gone wrong – we wake in the night and feel sleepy during the day. Researchers from UC Irvine have researched and understood the cellular mechanisms involved in the body clock [circadian rhythm] functioning and also have identified new compounds that control it. Disorders triggered by circadian rhythm dysfunction, like insomnia, obesity, diabetes or even cancer, can potentially be treated after this.
“Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms,” said Sassone-Corsi, the Donald Bren Professor of Biological Chemistry and lead of the research team. “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.”
He added that up to 15 percent of our genes are controlled and coordinated by the day-night pattern of circadian rhythms.
Sassone-Corsi and colleagues found that the biological clock controls enzymes situated in the mitochondrion, a cellular structure devoted to energy metabolism. It turns the cells’ genes on and off based upon their energy usage [process of acetylation of proteins]. To track the energy usage of cells, the enzyme protein SIRT1 is involved.
“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.
To understand how to regulate SIRT1 activity, Sassone-Corsi teamed with scientists from GlaxoSmithKline to test proprietary small-molecule compounds that stimulate SIRT1.
In mouse studies, they could successfully control SIRT1-activating compounds, effectively gaining the ability to manage the body clock of the mouse.