Scientists have succeeded in greatly extending the lifespan of a simple worm through “genetic trickery” and hope to begin similar experiments on mammals, they say.

In a paper published Thursday in the journal Cell Reports, researchers at the Buck Institute for Research on Aging in Novato, Calif., said they had extended the lifespan of tiny Caenorhabditis elegans to the human equivalent of 400 or 500 years.

Normally, the 1-millimeter-long, translucent nematode lives just several weeks. However, by combining two genetic mutations that inhibit key molecules involved in insulin signaling, or IIS, and the nutrient signaling pathway know as Target of Rapamycin, or TOR, scientists saw a five-fold extension of longevity, wrote senior author and biologist Pankaj Kapahi.

Past studies on C. elegans in which researchers experimented with single mutations resulted in increased longevity as well, but not close to what Kapahi and his colleagues observed when they combined the mutations.


Mutations in TOR usually result in a 30% increase in lifespan; IIS mutations usually result in a doubling of lifespan. By combining the two mutations, researchers expected to see an increase of around 130%, not a five-fold increase.

“The two mutations set off a positive feedback loop in specific tissues that amplified lifespan,” Kapahi said.

Eventually, the researchers say they want to experiment with mice to determine whether the lifespan-extending synergy works on mammals.

“The idea would be to use mice genetically engineered to have suppressed insulin signaling, and then treat them with the drug rapamycin, which is well known to suppress the TOR pathway,” Kapahi said.

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