Internal Clock and Metabolism May Be Linked

March 20 (HealthDay News) -- A compound that plays an important role in coordinating people's circadian clocks and metabolism has been identified by U.S. researchers.

The circadian clock governs daily cycles of feeding, activity and sleep.

Researchers from Northwestern University and the Washington University School of Medicine said their finding of a connection between the circadian clock and metabolism in animals could improve understanding of circadian disruptions that often affect elderly people.

The team also said the compound they identified might offer a new drug target to treat metabolic disorders related to circadian disruption caused by shift work, obesity or diabetes.

The study of laboratory mice showed that circadian clock genes strongly regulate the production of nicotinamide adenine dinucleotide (NAD), which regulates the activity of an enzyme called SIRT1, an important regulator of aging, metabolism and longevity.

The discovery that NAD and SIRT1 function together as a molecular "switch" to coordinate the circadian clock with metabolic systems should increase understanding of how aging, metabolism and the circadian clock are interconnected, the researchers said.

"This is one of the sought-after links that couples changes with the cellular environment and nutrient state with changes in the internal clock," Dr. Joe Bass, an assistant professor of medicine, neurobiology and physiology at Northwestern and a co-senior author of the study, said in a university news release.

Bass and his colleagues also found that NAD levels vary according to an animal's internal clock -- the first evidence of a "metabolic oscillator," an oscillator that isn't part of the core circadian clock machinery.

The study was published online March 19 in Science.

"NAD is an essential nutrient in our bodies that controls the pace of metabolism and drives our daily cycles," Dr. Shin-ichiro Imai, an associate professor of developmental biology at Washington University and also a co-senior author, said in the news release. "If that important compound gets messed up, our daily rhythmic cycle also will get messed up, which can lead to serious disease and affect the aging process. It is very important to maintain this compound and its pathway."


SOURCE: Northwestern University, news release, March 19, 2009

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