By Michigan Medicine - U. of Michigan, Jan. 5, 2026
https://scitechdaily.com/scientists-uncover-a-hidden-switch-that-controls-longevity/
https://scitechdaily.com/scientists-uncover-a-hidden-switch-that-controls-longevity/
Scientists studying tiny worms uncovered a surprising connection between how organisms sense their environment and how long they live. The research shows that simple sensory signals like touch can shut down a key longevity gene that normally extends lifespan during dietary restriction.
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A tiny worm revealed how simple sensory signals can quietly switch longevity on or off.
The idea of extending life may be especially popular among modern tech circles, but the desire to stay young or live forever has fascinated humanity for thousands of years.
Many of the most reliable strategies scientists know for increasing lifespan, including long-term dietary restriction, are difficult and often uncomfortable to sustain.
Scientists Explore a Longevity Gene
New research from the laboratory of Scott Leiser, Ph.D., in the Molecular and Integrative Physiology Department at the University of Michigan Medical School, reveals how a single longevity-related gene connects behavior, environmental signals, and biology.
These discoveries help researchers better understand the internal processes that regulate lifespan and point toward ways to extend life without relying on extreme lifestyle changes.
What Worms Can Teach Us About Aging
One study, published in PNAS, examined how environmental cues and food availability influence longevity using a tiny worm (the popular research model species, C. elegans).
“Believe it or not, most of the central ideas and types of metabolism we study are conserved from worms to people,” said Leiser.
He explained that sensing the environment triggers hormone release in humans, including adrenaline or dopamine. Worms respond in a similar way, with neurons that detect environmental changes and adjust their physiology accordingly.
Earlier studies have shown that stressful conditions such as limited access to food can improve survival.
Related work in fruit flies by Scott Pletcher, Ph.D., a colleague of Leiser at U-M, found that simply smelling food was enough to cancel out those survival benefits.
One study, published in PNAS, examined how environmental cues and food availability influence longevity using a tiny worm (the popular research model species, C. elegans).
“Believe it or not, most of the central ideas and types of metabolism we study are conserved from worms to people,” said Leiser.
He explained that sensing the environment triggers hormone release in humans, including adrenaline or dopamine. Worms respond in a similar way, with neurons that detect environmental changes and adjust their physiology accordingly.
Earlier studies have shown that stressful conditions such as limited access to food can improve survival.
Related work in fruit flies by Scott Pletcher, Ph.D., a colleague of Leiser at U-M, found that simply smelling food was enough to cancel out those survival benefits.
How Touch Disrupts Longevity Signals
Leiser and project leader Elizabeth Kitto, Ph.D., with support from Safa Beydoun, Ph.D., wanted to know whether other sensory experiences, such as touch, could also interfere with the lifespan extension caused by dietary restriction, and how that might happen.
To investigate, the researchers placed worms on a surface covered with beads designed to feel like the E. coli they normally encounter while feeding.
This tactile stimulation alone reduced the activity of a longevity associated gene in the intestine (fmo-2) and weakened the lifespan benefits normally produced by restricted diets.
Leiser first identified fmo-2 in 2015 as a gene that is both required and sufficient for lifespan extension triggered by dietary restriction.
“The fmo-2 enzyme remodels metabolism, and as a result increases lifespan,” he explained. “Without the enzyme, dietary restriction does not lead to a longer lifespan.”
Further experiments showed that touch activates a signaling circuit involving cells that release dopamine and tyramine. This reduces fmo-2 activity in the intestine and limits the longevity effect of dietary restriction.
Leiser and project leader Elizabeth Kitto, Ph.D., with support from Safa Beydoun, Ph.D., wanted to know whether other sensory experiences, such as touch, could also interfere with the lifespan extension caused by dietary restriction, and how that might happen.
To investigate, the researchers placed worms on a surface covered with beads designed to feel like the E. coli they normally encounter while feeding.
This tactile stimulation alone reduced the activity of a longevity associated gene in the intestine (fmo-2) and weakened the lifespan benefits normally produced by restricted diets.
Leiser first identified fmo-2 in 2015 as a gene that is both required and sufficient for lifespan extension triggered by dietary restriction.
“The fmo-2 enzyme remodels metabolism, and as a result increases lifespan,” he explained. “Without the enzyme, dietary restriction does not lead to a longer lifespan.”
Further experiments showed that touch activates a signaling circuit involving cells that release dopamine and tyramine. This reduces fmo-2 activity in the intestine and limits the longevity effect of dietary restriction.
Potential Implications for Human Health
According to Leiser, one of the most important takeaways is that these sensory circuits are not fixed and may be adjustable.
“If we could induce fmo-2 without taking away food, we could activate the stress response and trick your brain into making you long-lived.”
Before that becomes possible, researchers need to understand the other roles fmo-2 plays in the body.
According to Leiser, one of the most important takeaways is that these sensory circuits are not fixed and may be adjustable.
“If we could induce fmo-2 without taking away food, we could activate the stress response and trick your brain into making you long-lived.”
Before that becomes possible, researchers need to understand the other roles fmo-2 plays in the body.
Behavioral Side Effects of Longevity Pathways
In a second study published in Science Advances, the research team showed that altering fmo-2 also changes behavior in clear ways.
Worms engineered to produce too much fmo-2 showed little reaction to both positive and negative environmental changes. They failed to avoid potentially harmful bacteria and did not slow their eating after a brief fast, unlike normal worms.
Worms that lacked fmo-2 entirely were also affected, exploring their surroundings less often than usual. In both cases, the behavioral changes were traced to shifts in tryptophan metabolism.
“There are going to be side effects to any intervention to extend life–and we think one of the side effects will be behavioral,” said Leiser.
“By understanding this pathway, we could potentially provide supplements to offset some of these negative behavioral effects.”
In a second study published in Science Advances, the research team showed that altering fmo-2 also changes behavior in clear ways.
Worms engineered to produce too much fmo-2 showed little reaction to both positive and negative environmental changes. They failed to avoid potentially harmful bacteria and did not slow their eating after a brief fast, unlike normal worms.
Worms that lacked fmo-2 entirely were also affected, exploring their surroundings less often than usual. In both cases, the behavioral changes were traced to shifts in tryptophan metabolism.
“There are going to be side effects to any intervention to extend life–and we think one of the side effects will be behavioral,” said Leiser.
“By understanding this pathway, we could potentially provide supplements to offset some of these negative behavioral effects.”
Looking Ahead in Longevity Research
Leiser plans to continue studying how the brain, metabolism, behavior, and overall health interact, with the goal of helping develop future drugs that target these natural biological pathways.
“Investigating all of the individual signals that our brain is responding to from the gut is a hot but not well understood area.”
Leiser plans to continue studying how the brain, metabolism, behavior, and overall health interact, with the goal of helping develop future drugs that target these natural biological pathways.
“Investigating all of the individual signals that our brain is responding to from the gut is a hot but not well understood area.”
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