umans as well. The gene also affects reproduction, but the new research shows that the gene acts at different stages in the lifecycle to control reproduction and lifespan, so the two effects can be decoupled, said Cynthia Kenyon, PhD, the Herbert Boyer Professor of Biochemistry and Biophysics at UCSF and senior author on the SCIENCE paper.

"A lot of evolutionary biologists predicted that you couldn't lengthen lifespan with out inhibiting reproduction," Kenyon said. "But that's not true. These worms live much longer than normal and they reproduce perfectly normally. They look great, they're vigorous. These animals are having their cake and eating it too."

"As we uncover more about how these and related genes function we hope to learn how youthfulness and longevity can be extended in humans without any side effects as well."

Kenyon made international news in 1993 when she discovered that blocking daf-2 activity in C. elegans -- more formally, Caenorhadtis elegans -- doubled the normal two-week life of the worms. Their added weeks were not spent as doddering old worms, either.

"You could look at them under the microscope and see that they were lively and youthful," Kenyon said. In the new experiments, Kenyon and her colleagues used a fairly new technique that allowed them to silence daf-2 or a second gene, daf-16, either just after the worms had emerged from eggs, or as young adults. All genes are made of DNA, but protein-making instructions are sent out of the nucleus in the form of a related molecule, RNA. The technique can partially disable, or "knock down" any given RNA sequence and hence any given gene simply by introducing double stranded RNA that matches it. The two strands separate when cleaved by an enzyme called Dicer, and one of the strands hybridizes with the animal's own RNA, leading to its degradation. Perhaps evolved as a viral strategy to attack and disable hosts, RNA interference, or RNAi as it is called, can be
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
24-Oct-2002

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