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Sirtuin protein has a new function; May play role in lifespan extension

Scientists from Johns Hopkins and the University of Wisconsin have discovered that a protein called Sir2, which is found in nearly all living cells, has a new function that might help explain how calorie restriction can increase lifespans for some animals, the scientists say. Their report appeared in the Dec. 20 issue of Science.

A number of laboratories have shown that restricting total calorie intake extends the lifespans of organisms ranging from yeast to laboratory animals. Others have shown that this effect requires Sir2's protein family, called sirtuins, and increased cellular respiration, which is the process of using oxygen to convert calories into energy.

Studying bacteria, the Johns Hopkins-Wisconsin team has discovered that sirtuin controls the enzyme that converts acetate, a source of calories, into acetyl-CoA, a key component of cellular respiration.

"Sirtuins are highly conserved across species, but this is a never-before-described ability of the protein," says Jef Boeke, Ph.D., professor of molecular biology and genetics at Johns Hopkins' Institute for Basic Biomedical Sciences. "If sirtuins modify this enzyme in other organisms, turning on production of acetyl-CoA, it could help explain why restricting regular sources of calories -- sugars and fats -- leads to extended lifespan in many kinds of organisms."

Identified in all living creatures, including single-celled organisms like bacteria and yeast, sirtuin proteins previously were known to play an important role in keeping regions of chromosomes turned off. By modifying the histone proteins that keep DNA tightly coiled, sirtuins prevent certain regions of chromosomes from being exposed to cells' DNA-reading machinery.

Sirtuin's new role in bacteria involves the same modification as its interaction with histone -- removing an acetyl group, a "decoration" added to a protein's sequence (like phosphate) -- but the targeted protein is involved in p
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
6-Jan-2003


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