Fruit flies tricked into feeling hungry end up living longer even when they eat plenty of calories.
The findings of a recent study by researchers from the University of Michigan in the US suggest the perception of insatiable hunger alone can trigger the anti-aging effects of intermittent fasting. The animal doesn't actually have to starve.
"We've sort of divorced [the life extending effects of diet restriction] from all of the nutritional manipulations of the diet that researchers had worked on for many years to say they're not required," says physiologist Scott Pletcher.
"The perception of not enough food is sufficient."
Work on fruit flies (Drosophila melanogaster) and rodents seems to suggest calorie restriction can extend life spans and promote good health. But these are still early days, and far more research is needed before the results can be extended to humans – especially since some studies have produced conflicting results, or even highlighted potential dangers.
To study the molecular mechanisms of fasting further, the researchers behind this latest investigation turned once again to the humble fruit fly.
In the past, fruit fly studies have helped scientists identify numerous neural signals for hunger and satiety in the brain. These creatures share 75 percent of the same disease-related genes as us, and their metabolisms and brains have useful similarities to those in mammals.
Branched-chain amino acids (BCAA) are essential nutrients that appear to trigger feelings of fullness in flies when consumed. Eating more BCAAs, therefore, reduces their feelings of hunger.
To explore how this might impact aging, researchers kept fruit flies hungry by giving them snacks low in BCAA.
Their hunger was gauged by how much the insects ate from a buffet of food hours after consuming the snack.
Flies that were fed a low-BCAA snack ate more food at the later buffet. They also targeted protein-heavy foods over carbohydrate-heavy foods – a sign that the flies were driven by a need-based hunger, not a want-based one.
So researchers went straight to the source. When the team directly activated the neurons in fruit flies that trigger hunger responses, they found these hunger-stimulated flies also lived longer.
"Thus," Pletcher and colleagues write, "the motivational state of hunger itself, rather than the availability or energetic characteristics of the diet, might slow aging."
Further experiments showed lowering BCAA in flies' diets also led to their hunger neurons fashioning modified support proteins called histones, which bind to DNA and help regulate gene activity. The researchers think these modified histones might be the link between diet, hunger responses and aging. Interestingly, past studies have linked an increasing histone supply to an extended lifespan.
In light of the findings, researchers think chronic hunger might be an adaptive response, "mediated by modifications to histone proteins in discrete neural circuits, that slows aging."
The findings could help explain why low-BCAA diets seem to be good for our own health. Perhaps they provide the body with sufficient nutrients, while not quieting hunger signals in the brain completely.
Of course, that idea needs a lot more testing. One study on fruit flies isn't going to cut it.
For now, the researchers are interested in exploring whether the health of fruit flies is tied to eating for pleasure as well as for necessity.
The study was published in Science.