Almost a decade ago, Leonard Guarente at Massachusetts Institute of Technology found a gene called SIR2 in brewer’s yeast that, when mutated, seemed to extend the yeast’s life.

Cynthia Kenyon, a researcher at the University of California in San Francisco, found a life-extending gene in C. elegans, a tiny species of worm. Amazingly, the two genes were almost exactly the same–meaning they had been conserved through millions of years of evolution. Guarente and Kenyon are among the co-founders of Elixir Pharmaceuticals, a startup that hopes to turn its work into medicines to slow aging and fight a litany of diseases from cancer to heart disease and diabetes.



Guarente’s yeast lived longer when they were given less food, and the underlying mechanism seemed to be that starvation tripped SIR2. But extending that concept to mammals was more difficult. Now, the study in Nature by Pere Puigserver, a biochemist at Johns Hopkins University, has not only made that connection, but helped explain exactly what role the gene plays in mammals and possibly people.



Puigserver and his colleagues found that SIRT1, the mammal version of the SIR2 gene, was turned on in the livers of mice when they were put on a calorie-restricted diet. That set off a cascade of other genes, including PCG1, which is important in the regulation of blood sugar.



What seems to be happening, Puigserver says, is that SIRT1 tells the liver to start making sugar. Most of the body’s organs can keep running off fat if caloric intake is restricted, but the brain can’t. The genetic domino effect that his team uncovered may have less to do with extending life, he says, then with making it possible to survive caloric restriction at all. The life-extending results of caloric restriction could still be caused by something else. For instance, eating food may introduce substances that speed up chemical reactions in the body, making disease more likely.



Puigserver sees his discovery as a possible pathway to diabetes genes. Guarente sees even more potential. “It really suggests we’re confirming an important pathway here,” he says. Guarente feels that drugs that target SIRT1 might slow aging and have wide effects on other, more testable diseases, such as cancer and heart disease.



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