Longevity By A Nose -- Or Odorant Receptor

In a report that appears online today in the journal Science Express, Dr. Scott Pletcher, assistant professor in the Huffington Center on Aging and Department of Human and Molecular Genetics at BCM, and his colleagues found that when the calorie-restricted flies were exposed to the odor of yeast paste (although they did not eat it), they did not live as long as insects who were on identical diets but who were not exposed to the odor.

"Odorants limit the benefits of calorie restriction," Pletcher said.

Calorie restriction is a manipulation that has been shown to lengthen the lives of many different organisms, but the mechanisms through which this is achieved remains largely unknown. Moreover, the fact that reduced calories extend lifespan seems counterintuitive.

However, said Pletcher, dietary restriction does extend the lives of mice, and some data suggest that it also works in primates as well. How it works is not understood. Many feel that it works "through reduced energy," said Pletcher. "Our work argues that reduced perception plays a role as well."

"There may be a signaling mechanism that makes the organism operate more robustly when there are few resources (such as food)," said graduate student Sergiy Libert, who is lead author of the Science Express study. "Activating that signaling might be enough to provide the advantage and extend longevity."

In his study, he said, "Flies that could smell rich food in the environment lived shorter lives than flies who ate the same amount of food but were not exposed to the odorant. The perception of a rich environment was sufficient to shorten the lifespan."

In the second part of the study, the scientists tested fruit flies or Drosophila melanogaster that could not perceive odors well. The gene Or83b was mutated in these insects, leaving the flies with a severely reduced sense of smell, although they can smell some things.

"These flies appear to be much longer-lived," said Libert. "There was as much as a 57 percent lifespan extension." Most fruit flies live about 60 days. These lived longer than 80.

The researchers also found other differences in the flies who could not smell. The slightly obese female flies stored more triglycerides (which could then be used for energy). The flies that could not smell were also more stress-resistant.

"If you expose them to 100 percent oxygen, which is toxic they survive very well," said Pletcher.

Pletcher, Libert and their colleagues do not know how applicable this finding is to higher-level organisms such as mice, primates and humans. For example, said Pletcher, a gene such as Or83b has not yet been described in mammals, which have hundreds of odor receptors, many of which have not been carefully studied.

They hope to figure out how exactly odors in general affect longevity in the fly and possibly extend that understanding to other organisms -- even humans.

Although a gene such as Or83b has not yet been described in mammals, Pletcher, Libert and their colleagues suggest that this finding may be applicable in higher-level organisms such as mice, primates and humans, all of which have hundreds of odor receptors, many of which have not been carefully studied.

Pletcher said Dr. Gregg Roman, assistant professor of biology and biochemistry at the University of Houston, played a major role in the research. Others who took part included Jessica Zwiener and Xiaowen Chu, both of BCM, and Wayne VanVoorhies, of New Mexico State University.

Funding for this work came from the American Federation for Aging Research/Glenn Foundation, Ellison Medical Foundation and the National Institute on Aging of the National Institutes of Health.