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Eliminate Data Analysis Bottlenecks in Drug Discovery

volved in cellular aging and responding to calorie intake in mammals for the first time. In bacteria and yeast, the equivalent of sirtuin1 is already known to help slow processes linked to cellular aging when food is scarce, an effect that extends the single-celled organism's lifespan.

"We now know that sirtuin1 is directly involved in the response to calorie restriction in mammals and in processes involved in cellular aging," says Puigserver. "But we still don't know whether sirtuin1's activity affects lifespan in mammals."

There is a precarious anecdotal link, however. In 2003, other scientists reported that a compound found in red wine activated yeast's sirtuin1-equivalent and extended the organism's lifespan. Moving up the food chain, decades of reports have shown that drinking moderate amounts of red wine is associated with a longer life for people.

But at this point, knowing for sure whether sirtuin1 helps extend lifespan (an organism issue) or is merely involved in cellular aging (a cell-by-cell issue) in mammals will take much more work. Sirtuin1's potential as a target for treating diabetes is much closer, says Puigserver.

The researchers are now probing the pyruvate-sirtuin1 connection more closely and looking for more details of the sirtuin1-PGC1 interaction. Also on the to-do list: examining sirtuin1 and PGC1 in other tissues, particularly muscle and fat, two other energy-producing tissues in mammals.

The study was funded by the Ellison Medical Foundation, the American Federation for Aging Research, and start-up funds from the Department of Cell Biology at the Johns Hopkins School of Medicine.

Authors on the paper are Rodgers, Puigserver and Carlos Levin of Johns Hopkins; and Wilhelm Haas, Steven Gygi and Bruce Spiegelman of Harvard Medical School.


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