Deactivation of a protein in roundworms increases their lifespan, most likely mediating the effects of calorie restriction, scientists from the Salk Institute of Biological Studies have found.
Previously, researchers knew hunger promoted longevity by activating an enzyme called AMPK.
"We knew AMPK was a major energy sensor but didn't know what it was talking to. Our goal was to understand the genetic circuitry that registered that response," said Howard Hughes Medical Institute investigator Andrew Dillin.
The team fed worms an inhibitory RNA engineered to deplete them of CRTC1 protein. When they measured the worms' lifespan-normally about 3 weeks-they found that worms fed the anti-CRTC1 RNA lived a whopping 40 percent longer, suggesting that AMPK retards aging by antagonizing CRTC1 activity.
AMPK deactivated CRTC1 by adding phosphates to a specific region of the CRTC1 protein, an effect equivalent to eliminating CRTC1 altogether.
Likewise, when the worms were fed an inhibitory RNA depleting them of an enzyme that lops off the CRTC1 phosphates, they lived longer.
"What we have identified is a binary switch that turns the aging process on and off," said Dillin.
"Aging is a risk factor for a number of pathological conditions-if you could find a way to control this switch you could ameliorate a plethora of age-related diseases," he added.
"Whether you are talking about yeast, worms, Labradors, or rhesus monkeys-dietary restriction is the best intervention we have so far against age-related conditions like neurodegeneration, cancer and diabetes," said William Mair, a postdoctoral fellow in the Dillin lab.
"Our goal now is to use information we have derived from worm studies to find a way to treat many of these diseases with one magic bullet."
The study appears in the February 17, 2011 issue of Nature.