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RNAi Technology Reveals Molecular Secrets of Aging


RNAi just may be the string that pulls back the curtain on the secrets of aging and reveals a molecular fountain of youth: A team of modern-day Ponce de Leons at the University of California, San Francisco, report in a recent issue of Science using the technology to identify transcription factors in C. elegans that, when stimulated, increase lifespan and stop aging.

"We think we've found an important physiological explanation for both aging and age-related disease," said head researcher Cynthia Kenyon, in a statement. "The question of why older people are more susceptible to so many diseases has been a fundamental, unsolved problem in biology. Our findings suggest a beautiful molecular explanation, at least for this protein-aggregation disease."

Kenyon, along with first author Ao-Lin Hsu and Colleen Murphy, used RNAi to knock out the gene HSF-1 and found that the aging of tissue was accelerated and the organism had a shortened lifespan. Further RNAi experiments on this gene in combination with another transcription factor, DAF-16, showed that these two appear to work together. Finally, overexpression of these genes also led to increased lifespan and delayed tissue aging in C. elegans.

The group wrote that overexpression of these genes leads to an increase in certain heat shock proteins, which delay the aggregation of polyglutamine-expansion proteins.

"By preventing damaged and unfolded proteins from aggregating, this one set of proteins may be able to stave off both aging and age-related disease," Kenyon explained. "The small heat-shock proteins are the molecular link between the two."

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