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Roundworms provide link between diet and lifespan

Why is it that people who eat so little that they appear to be nearing starvation can actually live longer than the rest of us?

Dietary restriction is a well-known way of extending lifespan and postponing age-related disease in many species, including yeast worms, flies and rodents. But not until a recent study by Scripps Florida investigator Dr. Matthew Gill did scientists have a clue about why.


Dr. Gill, Assistant Professor at Scripps Florida

The recent study identifies a new role for a biological pathway that not only signals the body's metabolic response to nutritional changes, but also affects lifespan.

The study by Dr. Gill, an assistant professor in the Scripps Research Department of Metabolism and Aging and scientists at the Buck Institute for Research on Aging, used nematodes, or roundworms, which are a widely accepted model for human aging research.

"We've been able not only to identify some of these molecules for the first time in the worm, but also to show they act as a signal of nutrient availability and ultimately influence the worm's lifespan," said Dr. Gill. "What makes this important is that the same molecules are present in both humans and [the worms], so these molecules may play similar roles in both organisms."

The molecules identified in the new study are N-acylethanolamines (NAEs), a group of signaling molecules derived from lipids that help indicate nutrient availability in the environment and maintain an animal's internal energy balance. In the study, Dr. Gill and his colleagues showed that there are fewer NAEs in a worm when its diet is restricted, and that having fewer NAEs when there is plenty of food is enough to extend the animal's lifespan.

"It is well known that if you put [a nematode] on a restricted diet, you can extend its lifespan by 40 to 50 percent," Dr. Gill said. "However, we were amazed to see that if you add back just one of these NAE molecules…it completely abrogates the lifespan extension."

Importantly, this particular NAE is similar to endocannabinoids in mammals, which regulate many different physiological processes, including nutrient intake and energy balance, as well as inflammation and neuronal function.

"The identification of other components of a novel endocannabinoid system in the worm now brings a new model system to the many researchers studying NAE and endocannabinoid physiology," Dr. Gill said.

Intriguingly, the study also established a link among fat, NAE levels, and longevity. Other studies in rodents have shown that the availability of fatty acids can influence NAE levels. However, Dr. Gill and his colleagues found that in a genetically altered strain of roundworm, the inability to produce certain polyunsaturated fatty acids was not only associated with a reduction in levels of specific NAEs, but also with lifespan extension. He added that the study's findings could shape future drug development efforts to influence aging and age-related diseases.

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