Smelling food can reduce fly lifespan

The smell of food can affect the lifespan of flies and even partially reverse the life-prolonging effects of dietary restriction, scientists report this week in Science. These findings suggest the beneficial effects of caloric cutbacks on lifespan may not only depend on the decreased presence of food, but also on the decreased perception of it.

"This work provides an important first step into understanding how neural circuits may regulate lifespan in the fly," coauthor Scott Pletcher at the Baylor College of Medicine in Houston told The Scientist.

In a 2002 study comparing whole-genome expression patterns of long-lived diet-restricted Drosophila and fully fed flies, Pletcher and his colleagues found that both availability of food and age strongly affected genes encoding proteins that bound to aroma compounds or odorants, suggesting a link between smelling food and lifespan.

To investigate whether smelling food-related odors could affect fly longevity, the researchers measured Drosophila lifespans in the presence and absence of yeast odorants. They found the odorants reduced lifespan in diet-restricted flies from two lab strains to varying degrees, but by as much as 6 to 18 percent in one strain. The flies' lifespans became even shorter when they received yeast paste.

The odorants did not alter feeding behavior. They also did not affect lifespan when flies were fully fed, meaning that the odorants were not toxins that generally cut down lifespan.

To see if losing the sense of smell could increase lifespan, the researchers used Or83b knockout flies from the lab of Leslie Vosshall at Rockefeller University in New York. (Or83b, unlike the other 62 putative Drosophila odorant receptors, is broadly expressed throughout olfactory tissues.)

Relative to wild-type flies, fully-fed female Or83b-null fruit flies showed a 56 percent increase in median lifespan. In fully-fed males, the effect was smaller than in females, but males without Or83b showed an up to 42 percent increase in lifespan. Flies that were heterozygous for the mutation exhibited intermediate longevity, and expressing a Or83b transgene in mutant flies restored normal lifespan.

Lifespan further increased in Or83b-null flies after dietary restriction, suggesting that odors affect longevity largely, but not exclusively, through a pathway independent of diet.

"If it works in flies, it probably works in us. There are probably neural circuits of aging in humans that remain to be discovered, and these results give us a model to go forward with," Marc Tatar at Brown University in Providence, R.I., not a coauthor, told The Scientist.

Previous research had shown that destroying sensory neurons in the worm C. elegans could modify aging and longevity, in part by acting on insulin signaling. However, Pletcher and his colleagues found that Or83b -null flies, with their putative compromised sense of smell, exhibited normal expression levels of insulin-like peptides. The researchers also did not see any changes in the expression of Thor, the primary target of insulin sensor dFOXO.

While these results suggest olfactory regulation of aging in Drosophila may work largely independently of insulin signaling, they don't "rule out" that insulin plays some role, Pletcher said. Other pathways through which smells might help regulate aging include Sir2, he added.

To further investigate the role of insulin signaling in the aging-olfactory connection, Pletcher and his colleagues are conducting experiments crossing dFOXO and Sir2 mutants with Or83b-null flies. Future research may investigate whether specific odorant receptors can also impact longevity, Pletcher added.

"The olfactory system of the worm is very different from the olfactory system of the fly. The fly's is very much like that of vertebrates," Michael Grotewiel at Virginia Commonwealth University in Richmond, who did not participate in this study, told The Scientist. "The fact that knocking out the olfactory systems dramatically affects lifespan in worms and flies is fascinating, and suggests a striking conservation of the physiological mechanisms that impact lifespan across a wide range of species."

Charles Q. Choi
cchoi@the-scientist.com

Links within this article:

S. Libert et al. "Regulation of Drosophila lifespan by olfaction and food-derived odors," Science, published online ahead of print Feb. 1, 2007.
http://www.sciencemag.org

SJ Olshansky et al, "The longevity dividend," The Scientist, March 1, 2006.
http://www.the-scientist.com/article/display/23191

Scott Pletcher
http://www.hcoa.org/scott/bio.asp

S.D. Pletcher et al. "Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster." Curr. Biol., 12:R311-2 712, April 30, 2002.
http://www.the-scientist.com/pubmed/12007414

Leslie Vosshall
http://www.rockefeller.edu/research/abstract.php?id=156

G. Flores, "Fast track to longevity," The Scientist, March 7, 2005
http://www.the-scientist.com/article/display/15122/

M. Bucci. "Being young means feeling young," The Scientist, Feb. 16, 2004.
http://www.the-scientist.com/article/display/14440

M.W. Anderson. "Sir2: Scrambling for answers." The Scientist, December 6, 2004.
http://www.the-scientist.com/article/display/15122/

Michael Grotewiel
http://www.gen.vcu.edu/faculty/faculty/grotewiel.html