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Smell Less, Live Longer

The smell of a Big Mac makes your mouth water, but your arteries are safe if you buy the salad, right? Maybe not. A new study has identified a specific food odor that makes dieting fruit flies die young. The results suggest that certain odors—or drugs that block us from sensing them—might one day help prevent disease and extend lives.

For more than a decade, scientists have known that a low-calorie diet lengthens the lives of many organisms, including yeast, fruit flies, monkeys, and perhaps humans. But the connection may have as much to do with smelling as it does with eating. In 2004, for example, molecular geneticist Cynthia Kenyon of the University of California, San Francisco, discovered that removing certain olfactory neurons not only blocks roundworms’ sense of smell but also prolongs their lives. And a few years later, geneticist Scott Pletcher of the University of Michigan Medical School, biologist Gregg Roman of Baylor College of Medicine, and their colleagues shortened the life span of fruit flies by wafting the smell of live yeast—a tasty treat—toward them while they were on a diet.

Pletcher and colleagues suspected that a specific odor was at work, but they didn't know which one. In the meantime, other scientists had identified a receptor in a group of neurons that enable fruit flies to smell carbon dioxide, which signals the presence of a good meal of tasty yeast.

To see if carbon dioxide was the key to cutting short the dieting flies’ lives, Pletcher and Roman obtained mutant flies that lacked the CO2 receptor. They found that the mutant flies lived up to 30% longer than normal flies even on a standard diet. They then induced carbon dioxide-sensing neurons to self-destruct, with similar life-extending results. Finally, when the researchers restored the gene for the CO2 receptor back into mutant lines of flies, the flies lived no longer than their normal cousins.

The mutant flies that couldn’t smell carbon dioxide not only lived long lives but also remained strong and resilient by several measures. For example, they stored more fat, a physiological state that helps flies resist stress, and the females produced at least as many offspring as normal flies, the researchers report online today in PLoS Biology.

Blocking the perception of CO2 may trick the animals into thinking there’s no food around, which would slow down their metabolism and conserve their nutritional supplies, just as hungry animals do, the authors write.

“It’s a very exciting result,” says evolutionary biologist Tadeusz Kawecki of the University of Lausanne in Switzerland. If physiology and metabolism can be altered by particular odors, then drugs that block particular odors could also alter physiology and metabolism in people, which could help prevent disease or extend lives, he adds. “At this stage, it seems far-fetched, but it clearly works for flies.”