Drugs tailored to block specific genes or proteins involved in nutrient-sensing pathways would have much more appeal than reducing what one eats. To achieve anti-aging benefits, it's thought that people would have to restrict food intake by 30 to 40 percent, a grim prospect. In addition, drugs might be designed to avoid other disadvantages of this level of dietary restriction, which include reduced fertility.

C. elegans is a tiny roundworm, a nematode whose two-week lifespan is a great advantage for scientists studying aging. The 1-millimeter-long transparent worms have other advantages, too. C. elegans exhibits many age-associated changes observed in higher organisms.

"Many genes identified in C. elegans to control the speed of aging turned out to be evolutionarily conserved, meaning that you can find them in other animals, too. And many are very similar to those found in humans," Hsu says.

Research details

Hsu and his team created different mutant strains of roundworms, some with drr-2 genes silenced and others in which the gene was over-expressed. They wanted to learn whether inactivating drr-2 is essential for TOR to influence longevity, and found that it was. Other newly discovered genes may affect TOR signaling as well. But Hsu's team has found a promising lead for anti-aging drugs of the future: They were able to show that silencing drr-2's action alone was sufficient to make worms live longer than wild-type C. elegans used as controls.

"It is known that reduction of TOR signaling in response to a change in the environment or genetic manipulation triggers a cascade of cellular signals that alter cell growth, metabolism, and protein synthesis, and decrease the pace of aging," says Hsu. "Our recent studies have shown that drr-2 might play a pivotal role in the TOR signaling network to control protein synthesis as well as longevity."

Source: University of Michigan Health System

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