Navigation Links
Circadian rhythms can be modified for potential treatment of disorders

Irvine, Calif., Jan. 22, 2013 UC Irvine-led studies have revealed the cellular mechanism by which circadian rhythms also known as the body clock modify energy metabolism and also have identified novel compounds that control this action. The findings point to potential treatments for disorders triggered by circadian rhythm dysfunction, ranging from insomnia and obesity to diabetes and cancer.

UC Irvine's Paolo Sassone-Corsi, one of the world's leading researchers on the genetics of circadian rhythms, led the studies and worked with international groups of scientists. Their results are detailed in two companion pieces appearing this week in the early online edition of the Proceedings of the National Academy of Sciences.

"Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms," said Sassone-Corsi, the Donald Bren Professor of Biological Chemistry. "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 people's genes are regulated by the day-night pattern of circadian rhythms.

In one study, Sassone-Corsi and colleagues found that the biological clock controls enzymes localized in the mitochondrion, a cellular structure devoted to energy metabolism. This government occurs through acetylation of proteins, a process that operates as a switch to turn genes on and off in cells based upon the cells' energy usage.

Some of the most important acetylation events in cells are dictated by an enzyme protein called SIRT1, which senses energy levels in the cell. Its activity is modulated by how many nutrients a cell is consuming. It also helps cells resist oxidative and radiation-induced stress. SIRT1 has been linked to the inflammatory response, diabetes and aging.

Sassone-Corsi first showed the circadian rhythm-metabolism link in 2008 and 2009, and in this study, he and his colleagues reveal the metabolic pathways through which SIRT1 works.

"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 contributed to the study titled "Pharmacological modulation of circadian rhythms by high-affinity SIRT1 activators." The National Institutes of Health and INSERM provided support.


Contact: Tom Vasich
University of California - Irvine

Related biology news :

1. Circadian rhythms have profound influence on metabolic output, UCI study reveals
2. Brandeis scientists win prestigious prize for circadian rhythms research
3. Scientists discover molecular link between circadian clock disturbances and inflammatory diseases
4. Zebrafish study explains why the circadian rhythm affects your health
5. Metabolism in the brain fluctuates with circadian rhythm
6. Musical duets lock brains as well as rhythms
7. Rhythms in the brain help give a sense of location, study shows
8. Genetically modified corn affects its symbiotic relationship with non-target soil organisms
9. Transplanted genetically-modified adipose cells offer potential therapy for liver diseases
10. Epigenetic signatures direct the repair potential of reprogrammed cells
11. New insight into mechanisms behind autoimmune diseases suggests a potential therapy
Post Your Comments:
(Date:11/12/2015)... 11, 2015   Growing need for low-cost, ... has been paving the way for use of ... discrete analytes in clinical, agricultural, environmental, food and ... used in medical applications, however, their adoption is ... to continuous emphasis on improving product quality and ...
(Date:11/10/2015)...  In this report, the biomarkers market ... type, application, disease indication, and geography. The ... consumables, services, software. The type segments included ... biomarkers, and validation biomarkers. The applications segments ... drug discovery and development, personalized medicine, disease ...
(Date:11/9/2015)... , Nov. 09, 2015 ... the addition of the "Global Law ... their offering. --> ) ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) has ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... November 25, 2015 , ... ... were featured on AngelList early in their initial angel funding process. Now, they ... for individuals looking to make early stage investments in the microbiome space. ...
(Date:11/24/2015)... FAR HILLS, N.J. (PRWEB) , ... November 24, 2015 , ... ... University, as the recipient of the 2016 USGA Green Section Award. Presented annually since ... of golf through his or her work with turfgrass. , Clarke, of ...
(Date:11/24/2015)... , Nov. 24, 2015 Halozyme Therapeutics, Inc. (NASDAQ: ... Conference in New York on Wednesday, December ... Helen Torley , president and CEO, will provide a corporate overview. ... New York at 1:00 p.m. ET/10:00 a.m. PT . ... investor relations, will provide a corporate overview. --> th ...
(Date:11/24/2015)... ... 24, 2015 , ... Copper is an essential micronutrient that ... proteins, copper is also toxic to cells. With a $1.3 million award from ... conduct a systematic study of copper in the bacteria Pseudomonas aeruginosa (P. aeruginosa), ...
Breaking Biology Technology: