PHILADELPHIA -- In recent years, scientists have learned that members of a family of enzymes known as sirtuins play critical roles in a wide array of vital life processes, including metabolism, aging, and gene expression. Some studies have shown that low-calorie diets that extend life also boost sirtuin activity dramatically, suggesting an intriguing link between metabolism and aging through sirtuins. And in September, a team of investigators found that a sirtuin-activating compound found in red wine increased the life span of yeast cells by more than two-thirds.

Humans have at least seven different sirtuins performing different tasks, and given the evident importance of the work they do, researchers have been trying to better understand how they function. Insights into their mode of action could represent early steps toward developing a novel class of drugs that might promote health in various ways.

Now, structural biologists at The Wistar Institute studying the role of sirtuins in gene expression specifically in turning genes off report new findings that significantly illuminate how sirtuins work. The results point to a mechanism of action likely to be general for the entire sirtuin enzyme family and may offer the beginnings of an explanation for how metabolism and aging may be linked through the mechanisms that control gene expression. The research is featured on the cover of the November issue of the journal Structure.

"We've known for some time that there is a connection between low-calorie diets and longevity," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program and senior author on the Structure study. "More and more, too, it looks like there is a real link between metabolism and gene expression. By providing a clearer picture of how sirtuins operate generally, our findings may begin to suggest how these three areas metabolism, gene expression, and aging intersect at the molecular level." <
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
4-Nov-2003

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