September 09, 2016 6:00 AM

Protein’s Pleasures and Perils: Study Reveals Clues to Appetite and Aging

Serotonin may motivate fruit flies to search for protein-rich foods. This, in turn, may explain something about how food affects longevity.

If you’re a human who’s hungry, a handful of nuts, a piece of cheese or a nice juicy steak may hit the spot. If you’re a fruit fly, a nibble of yeast will do the trick.  

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Both beings seek protein-rich foods when running on empty. But why? And what does that preference mean for the odds of living a longer life, whether it’s measured in decades for a human, or days for a fly?  

New research from a University of Michigan Medical School team suggests for the first time that a brain chemical may have a lot to do with both questions.

In a new paper in the journal eLife, U-M scientist Scott Pletcher, Ph.D., and his team demonstrate the key role that serotonin plays in the feeding habits and life spans of fruit flies. The paper’s first author is Jennifer Ro, Ph.D., now at Harvard Medical School.

"We found that the serotonin pathway is important for interpreting the composition of the food, as well as the reward that drives consumption of the food."
Scott Pletcher, Ph.D.

Reward drives consumption

Serotonin is a reward chemical; it’s released in response to an action. It travels between brain cells and produces a sense of reward or even pleasure.

Pletcher and his team report that it appears to play a key role in fruit flies’ strong tendency to seek out protein, not sugars, when they’ve been food-deprived for a while. In other words, it affects the value flies place on protein at that time — meaning it’s somehow tied to how flies figure out which foods contain protein in the first place.

The reward flies got from eating protein also appears to influence how quickly the flies aged. When the reward was blocked, the flies ate just as much food as before in their normal diets — but lived far longer.

In fact, nearly twice as long, just from blocking a single serotonin receptor found on the surface of only about 100 neurons in their brains.

“This work builds on previous findings that the perception of food modulates aging in much the same way as dietary intake, but the brain regions and systems involved in this have been unknown,” says Pletcher. “We found that the serotonin pathway is important for interpreting the composition of the food, as well as the reward that drives consumption of the food.”

Protein-rich diets have previously been found to lead to shorter life spans, Pletcher notes. “These results suggest that serotonin is directly involved in this process, though we have not yet found the mechanism,” he says.

The new results add to a changing scientific view of how food affects health and life span. The way animals respond to nutrients, including detecting them in their environment and seeking out certain ones during different times, goes far beyond simply seeking calories of any kind.

Although it’s far too soon to apply their findings to our understanding of human feeding patterns or longevity, Pletcher says the serotonin reward system, as well as many other basic systems, in fruit flies is very similar to that in mammals, including humans.

Understanding the link between food and life span

The brain’s ability to register that an animal has eaten enough of a certain nutrient is key to its ability to signal — via reward pathways — that an earlier hunger has been satisfied, Pletcher says.

To manipulate this in fruit flies, the researchers edited the genes involved in the serotonin system and the flies’ access to different types of food via a special chamber.

Called the FLIC, or Fly Liquid-food Interaction Counter, this device allowed them to continuously monitor food preferences for each micro-meal and to identify how and when flies were rewarded by a protein-rich diet.

The team designed experiments to examine whether such nutritional rewards affect health and life span by providing flies just a sugary diet, just a protein-focused diet or a diet that gave them a choice of three options: the two single-nutrient diets plus a mixed diet.

Even when that reward pathway was blocked in the fruit fly experiments, the flies stopped eating for other reasons — they didn’t stuff themselves dangerously. But the inability to sense the special reward that they usually would have gotten from eating protein did something to influence their life span. Now, the Pletcher group is working to determine just what that might be.

In the meantime, humans whose stomachs are rumbling and brains are sending a message of serious hunger should feel free to satisfy that craving for a protein-rich snack or meal, without life span concerns. After all, human lives are much more complex than those of fruit flies.

More research in fruit flies may help us understand why protein seems the most appealing or causes a unique sense of reward.

Says Pletcher, “This paves the way for future work to understand how the brain mechanisms that allow animals to perceive and evaluate food act to control life span and aging.”