Summary: Drugs that block serotonin and dopamine enable the life-extending effect of the FMO protein in C. elegans, even in the presence of the smell of food.
Source: University of Michigan
It is common knowledge that a healthy diet is the key to a healthy life. And while many people follow specialized diets to reduce or improve their overall health, researchers interested in aging have actively studied the effects of food restriction and fasting on lifespan.
“There’s a concept called hormesis in biology, the idea of which is that what doesn’t kill you makes you stronger,” said Scott Leiser, Ph.D., assistant professor of molecular and integrative physiology and internal medicine at the ‘University of Michigan. Medicine School.
“One of the most studied stresses is dietary restriction, which has been shown in many different organisms to extend lifespan and in people to improve health.”
However, as anyone dieting to lose weight can attest, the mere smell of delicious food can be enough to break the will. A previous study by Leiser’s colleague Scott Pletcher, Ph.D., also from the Department of Molecular and Integrative Physiology, found that in fruit flies, attractive food odors are sufficient to blunt the life-prolonging effect 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 understand why this is the case and whether the phenomenon could be blocked with medication.
In the roundworm C. elegans, the extension of lifespan in response to environmental stressors such as dietary restriction involves the activation of a gene called fmo-2. The team used the transparent nature of C. elegans to be able to see, in real time, FMO protein levels.
When the worms were limited in the amount of food they could eat, the FMO protein, which was highlighted using a fluorescent marker, lit up “like a Christmas tree…c ‘was bright red,’ Leiser noted. However, when the worms were exposed to food odors, there was significantly less FMO activation, resulting in longer lifespan.
One of the main problems with dietary restriction as a potential approach to prolonging people’s lives is its difficulty. But, Leiser said, “what if you could give yourself a drug that would confuse your body into thinking you were restricting your diet?”
Building on previous research showing that neurotransmitters regulate longevity resulting from dietary restriction, the team looked at compounds known to act on neurons.
They found three compounds that could prevent reversal of fmo-2 induction in the presence of food: an antidepressant that blocks the neurotransmitter serotonin and two antipsychotic drugs used to treat schizophrenia, both of which block the neurotransmitter dopamine.
“We know that serotonin and dopamine are major 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 antagonize this suggests that you’re blocking some aspects of these pathways.” Ultimately, the drugs enabled the life-extending effect of FMO, even in the presence of the smell of food.
However, these specific drugs are unlikely to be prescribed for this effect, given their many potentially dangerous side effects. But they provide important clues to the fmo-2 activation pathway and its effect on life extension.
About this neuroscience research news
Author: Press office
Source: University of Michigan
Contact: Press Office – University of Michigan
Image: Image credited to Justine Ross, Michigan Medicine
Original research: Free access.
“Serotonin and Dopamine Modulate Aging in Response to Smell and Food Availability” by Hillary A. Miller et al. Nature Communication
Serotonin and dopamine modulate aging in response to smell and food availability
An organism’s ability to perceive and respond to changes in its environment is crucial to its health and survival.
Here we reveal how the most studied longevity intervention, dietary restriction, acts in part through a non-autonomous cell signaling pathway that is inhibited by the presence of appealing odors.
Using a gut reporter for a key gene induced by food restriction but suppressed by appealing odors, we identify three compounds that block the effects of food odors in C.elegansthereby increasing longevity as dietary restriction mimetics.
These compounds clearly implicate serotonin and dopamine in lifespan limitation in response to food odor.
We further identify a chemosensory neuron that likely perceives food odor, an enteric neuron that signals through the serotonin 5-HT1A/SER-4 receptor, and a dopamine neuron that signals through the dopamine DRD2/DOP- receptor. 3. Some aspects of this pathway are retained in D. melanogaster.
Thus, blocking food odor signaling through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of food restriction.
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