Protein Links Metabolism to Clock: Work Could Lead to Drugs for Obesity, Aging and Jet Lag

By Saey, Tina Hesman | Science News, August 16, 2008 | Go to article overview

Protein Links Metabolism to Clock: Work Could Lead to Drugs for Obesity, Aging and Jet Lag


Saey, Tina Hesman, Science News


Cue stomach rumbles SIRT1 sets internal clock To metabolism

Timing is everything, especially when it comes to basic biological functions such as eating, sleeping and liver activity. Scientists have known for ages that metabolism is tied to the body's daily rhythms but have not known how.

Now, two groups of researchers report in the July 25 Cell the discovery of a molecule that links metabolism to the circadian clock in mice. The missing link turns out to be a protein called sirtuin 1, or SIRT1, which is also a key regulator of aging.

Uncovering the mechanism that links metabolism and circadian rhythms could lead to drugs for combating obesity, aging and jet lag and for helping shift workers reset their body clocks.

"It's an interesting connection," says Herman Wijnen, a circadian geneticist at the University of Virginia in Charlottesville who was not involved in the new studies. "It helps us understand one important aspect of how clocks and metabolism relate to each other."

SIRT1 has also been a source of research interest because of its involvement in the effects of resveratrol, a molecule found in red wine and other foods that mimics the health benefits of a nutritious, calorie-restricted diet.

Body rhythms are governed by molecular clocks that take about a day to complete a full cycle, hence the label circadian. The clocks are composed of proteins whose concentrations or levels of activity rise and fall like the tides.

Most animals have a main pacemaker in the brain. Triggered by light, this clock can reset within a couple of days. But almost every cell in the body contains a clock, and these clocks are reset by the introduction of food, by a change in body temperature or by other metabolic signals.

For the body to function normally, all the cellular clocks must synchronize with the main clock in the head, says Ueli Schibler of the University of Geneva in Switzerland and coauthor of one of the studies. But the cellular clocks take longer to reset, a week or more. This mismatch between the cellular clocks and the brain clock is one reason for jet lag.

That's probably as it should be, Schibler says. "Imagine if you stand up in the middle of the night and eat a sandwich. You don't want your clock reset just because of one sandwich."

In 2006, researchers led by Paolo Sassone-Corsi, a molecular biologist at the University of California, Irvine and coauthor on the other Cell study, reported that a protein named CLOCK is a component in cellular clocks. It drums out the beat of circadian rhythm by chemically modifying a histone protein, which packages DNA in the cell. …

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