Calorie restriction (CR) extends lifespan in many organisms. Early on, we believed that the longevity benefits were due to the decrease in available energy and the concomitant slowing of metabolism — a hypothesis that might be paraphrased as “The candle that burns twice as bright burns but half as long.”

Genetic studies have revealed, however, that the life-extension due to CR is probably due to molecular sensors of available energy (or possibly even of single specific amino acids), which control the cellular signaling pathways that actually implement the CR phenotype. One implication of this idea is the hope that we might someday develop calorie restriction mimetics: drugs that would bypass the upstream sensors and activate the downstream effectors directly, allowing us to eat as much as we want while reaping the benefits of CR.

Further evidence that it’s not how much you eat, but how much you think you’re eating, comes from a recent report that the very smell of food can control lifespan in flies, regardless of what food the flies are actually consuming. From Libert et al.:

Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caeonorhabditis elegans, gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster, we show that exposure to nutrient-derived odorants can modulate lifespan and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b results in severe olfactory defects, alters adult metabolism, enhances stress resistance, and extends lifespan. Our findings indicate that olfaction affects adult physiology and aging in Drosophila possibly through perceived availability of nutritional resources and that olfactory regulation of lifespan is evolutionarily conserved.

So the flies smell the food; they think they’re getting fed; and they don’t live as long.

At this early stage, it’s anyone’s guess whether this sort of phenomenon occurs in mammals. If it does, one might speculate that individuals with damage to their olfactory sensors (i.e., noses) might reap some of the benefits of CR without alterations in diet.

One also wonders whether there might be odors that work in the other direction (what’s the opposite of a food smell?).

Might we someday boost lifespan by aromatherapy?

(For more on this story, see also Marc Tatar’s minireview, “A Smell to Die For,” in the March issue of Developmental Cell.)