A pair of new studies has revealed that environmental signals—specifically the sensation of touch—can override the genetic pathways that allow dietary restriction to extend lifespan, suggesting that longevity is shaped by the nervous system as much as by diet.
The research, led by Scott Leiser’s team at the University of Michigan, examined how environmental signals move through the nervous system to influence metabolism, behavior, and lifespan. One study, published in PNAS, shows that touch can cancel the lifespan extension induced by dietary restriction by suppressing the gene fmo-2, which is essential for dietary restriction’s effects.The other study, published in Science Advances, looks at how changes in this pathway affect worm behavior.
Together, the results suggest that it may be possible to influence longevity by targeting neural circuits, as opposed to just changing diet.
A Simple Organism With a Familiar Biology
Despite its modest size, the nervous system of the tiny worm C. elegans relies on many of the same signaling molecules as humans. Its neurons release chemicals such as dopamine and tyramine in response to cues like food, smell, and texture, triggering metabolic changes. Most pathways for nutrient sensing and stress response are shared between worms and mammals. This makes C. elegans a valuable model for studying aging.
Previous studies suggested that sensory cues can reduce the benefits of calorie restriction. For example, in fruit flies, just smelling food was enough to cancel out the lifespan extension from eating less. Leiser’s group wanted to determine whether touch could have a similar effect in worms and how this would involve the gene fmo-2, which is required for lifespan extension under dietary restriction.
Touch Cancels the Benefits of Dietary Restriction
To test this, the researchers placed worms on tiny beads that felt like E. coli, their usual food source. The worms did not eat the beads, but the sensation alone was enough to turn off fmo-2 in their intestines. As a result, the worms lost the lifespan extension commonly seen with dietary restriction.
The experiments revealed that the process begins in the nervous system. Touch activates a neural circuit that changes how certain neurons release dopamine and tyramine. These signals then reduce fmo-2 activation in the gut. Normally, this gene helps the animal adjust its metabolism during dietary restriction, enabling it to cope with the stress of reduced food intake. Without fmo-2, the worms cannot live longer on a restricted diet.
Leiser points out that the neural circuit controlling fmo-2 can be adjusted. If scientists can find a way to activate this gene without changing diet, it may be possible to trigger the protective metabolic state without requiring strict dietary restriction. However, more research is needed to understand how this pathway operates under different conditions.
A Gene With Behavioral Costs
The second study examined what happens when worms are engineered to overexpress fmo-2. Worms engineered to produce extra fmo-2 behaved differently. They failed to retreat from harmful bacteria and did not pause to feed after fasting. Worms without the gene also behaved differently, exploring their environment less than normal worms.
These changes suggest a trade-off. The pathway that extends lifespan also reduces some instinctive behaviors, likely by altering tryptophan metabolism. Therefore, any future therapies targeting this gene in humans would need to address possible side effects.
“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.”
A Complex Conversation Between Brain and Body
Together, the two studies demonstrate that the brain constantly interprets environmental signals and uses them to adjust the body’s metabolism. In C. elegans, the sensation of food alone can remove the benefits of dietary restriction. The same pathway that supports longevity also changes behavior, which can either help or harm survival depending on the situation.
For scientists studying aging, these findings open new directions for research. They show that sensory signals can override genetic pathways that control lifespan, and that these pathways are closely linked to behavior. The results also suggest that future treatments for longevity may need to focus on neural circuits as much as on diet or metabolism.
Leiser’s team plans to continue mapping how signals move between the brain, gut, and other tissues. As more of these interactions are uncovered, scientists may eventually find ways to activate the beneficial parts of the aging response while avoiding the negative trade-offs.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds a Master of Business Administration and a Bachelor of Science in Business Administration, as well as a certification in Data Analytics. His work combines analytical training with a focus on emerging science, aerospace, and astronomical research.