Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Circadian rhythms can be modified for potential treatment of disorders

23.01.2013
UCI-led studies identify cellular pathways involved in governing day-night pattern

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 Science.

“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.

About the University of California, Irvine: Founded in 1965, UC Irvine is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UC Irvine is among the most dynamic campuses in the University of California system, with more than 28,000 undergraduate and graduate students, 1,100 faculty and 9,400 staff. Orange County’s second-largest employer, UC Irvine contributes an annual economic impact of $4.3 billion. For more UC Irvine news, visit news.uci.edu.

News Radio: UC Irvine maintains on campus an ISDN line for conducting interviews with its faculty and experts. Use of this line is available for a fee to radio news programs/stations that wish to interview UC Irvine faculty and experts. Use of the ISDN line is subject to availability and approval by the university.

Tom Vasich | EurekAlert!
Further information:
http://www.uci.edu

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>