Serotonin and dopamine modulate aging in response to food smell and availability

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Summary: Drugs that block serotonin and dopamine enable the life-prolonging effects of the FMO protein in C. elegans, even in the presence of food odor.

Source: University of Michigan

It is well known that a healthy diet is the key to a healthy life. And while many people follow special diets to reduce or improve their overall health, researchers interested in aging have been actively studying the life-prolonging effects of dietary restrictions and fasting.

“There’s a concept called hormesis in biology, the idea of ​​which makes you stronger, which doesn’t kill you,” said Scott Leiser, Ph.D., assistant professor of molecular and integrative physiology and internal medicine at the University of Michigan Medical School.

“One of the best-studied stresses is dietary restriction, which increases lifespan in a wide variety of organisms and improves health in humans.”

However, as anyone on a weight loss diet can attest, the mere smell of delicious food can be enough to break one’s willpower. A previous study by Leiser’s colleague Scott Pletcher, Ph.D., also of the Department of Molecular and Integrative Physiology, found that in fruit flies, attractive food smells are sufficient to mitigate the life-prolonging effects of a restricted diet.

In a new study published in nature communicationLeiser, first authors Hillary Miller, Ph.D., and Shijiao Huang, Ph.D., and their team are building on this research to determine why this is the case and whether the phenomenon could be blocked with a drug.

In the roundworm C. elegans, lengthening lifespan in response to environmental stressors such as dietary restrictions involves activation of a gene called fmo-2. The team took advantage of the transparent nature of C. elegans to be able to see real-time levels of FMO proteins.

When the worms’ food supply was limited, the FMO protein, highlighted with a fluorescent marker, “glowed like a Christmas tree…it was bright red,” Leiser noted. However, when the worms were exposed to food odors, FMO was activated significantly less, resulting in a loss of life extension.

This shows a drawing of C elegans and food
In the roundworm C. elegans, lengthening lifespan in response to environmental stressors such as dietary restrictions involves activation of a gene called fmo-2. Photo credit: Justine Ross, Michigan Medicine

One of the main problems with dietary restriction as a potential approach to prolonging life in humans is how difficult it is. But, Leiser said, “what if you could give yourself a drug that would trick your body into thinking you were restricting your diet?”

Building on previous research showing that neurotransmitters regulate longevity resulting from dietary restriction, the team examined compounds known to act on neurons.

They found three compounds that might prevent reversal of fmo-2 induction in the presence of food: an antidepressant that blocks the neurotransmitter serotonin, and two antipsychotics used to treat schizophrenia, both of which block the neurotransmitter dopamine.

“We know that serotonin and dopamine are important players in the reward part of the brain and tend to be involved in satiety and food response signals,” Leiser said. “The fact that the drugs we found counteracted this suggests that they block aspects of these signaling pathways.” Ultimately, the drugs enabled FMO’s life-prolonging effects, even in the presence of food odor.

However, these specific drugs are unlikely to be prescribed for this effect as they have many potentially dangerous side effects. But they do provide important clues about the fmo-2 activation pathway and its effect on life extension.

About this news from neuroscientific research

Author: press office
Source: University of Michigan
Contact: Press Office – University of Michigan
Picture: Image credited to Justine Ross, Michigan Medicine

Original research: Open access.
“Serotonin and dopamine modulate aging in response to food smell and availability” by Hillary A. Miller et al. nature communication


abstract

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Serotonin and dopamine modulate aging in response to food smell and availability

An organism’s ability to sense and respond to changes in its environment is critical to its health and survival.

Here we show how the best-studied longevity intervention, dietary restriction, works in part via a nonautonomous cell signaling pathway that is inhibited by the presence of attractive odors.

Using an intestinal reporter for a key gene that is induced by dietary restriction but repressed by attractive odors, we identify three compounds that block the effects of food odor C. elegansthereby increasing longevity as mimetic dietary restrictions.

These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food odor.

We also identify a chemosensory neuron that is likely to perceive the smell of food, an enteric neuron that signals via the serotonin receptor 5-HT1A/SER-4, and a dopaminergic neuron that signals via the dopamine receptor DRD2/DOP-3. Aspects of this path are preserved in D. melanogaster.

Therefore, blocking food odor signaling by antagonizing serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction.

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