The pursuit of a longer life may currently be trending for tech bros, but the notion of a fountain of youth, or even immortality, has intrigued people for millennia.<\/p>\n
Yet, some of the more evidence-based methods to increase longevity, such as dieting, are decidedly unpleasant to maintain over time.<\/p>\n
Research from the lab of Scott Leiser, Ph.D., of Molecular and Integrative Physiology Department at University of Michigan Medical School, uncovers interesting connections between a longevity gene, behavior and the environment.<\/p>\n
The findings bring scientists closer to understanding the underlying biological mechanisms that might be exploited to extend life without the downsides.<\/p>\n
The first study, appearing in\u00a0PNAS, uses a worm (the popular research model species,\u00a0C. elegans) to further explain the effect of environmental cues and food access on longevity.<\/p>\n
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Believe it or not, most of the central ideas and types of metabolism we study are conserved from worms to people.”<\/p>\n
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Scott Leiser, Ph.D., Molecular and Integrative Physiology Department, University of Michigan Medical School<\/p>\n
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When we perceive the environment, we release hormones like adrenaline or dopamine. Worms do the exact same thing; their neurons respond to the environment and change their physiology accordingly,” he explained.<\/p>\n
Previous research has shown that stress like food scarcity can promote survival.<\/p>\n
Intriguingly, foundational work in flies from Leiser’s U-M colleague Scott Pletcher, Ph.D., showed that the mere smell of food can reverse this effect.<\/p>\n
Leiser, along with project leader Elizabeth Kitto, Ph.D., and with support from Safa Beydoun, Ph.D., wondered whether other sensory inputs, like touch, would also mitigate the life-extending effects of dietary restriction, and if so, how?<\/p>\n
To test this, they placed worms on a bed of beads with a texture similar to the\u00a0E. coli\u00a0buffet they would normally encounter during feeding.<\/p>\n
The touch of the beads was enough to blunt the expression of a gene in the intestine related to longevity (fmo-2)\u00a0and in doing so, reduced the life extension effect of dietary restriction.<\/p>\n
Leiser discovered that fmo-2 is a gene that is necessary and sufficient to extend lifespan downstream from dietary restriction in 2015.<\/p>\n
“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.”<\/p>\n
Specifically, their experiment showed that touch activates a circuit that modulates signals from cells that release dopamine and tyramine, which decreases intestinal fmo-2 induction and thus the longevity effect of a restricted diet.<\/p>\n
Most importantly for human health, the work demonstrates that these circuits can be manipulated, said Leiser.<\/p>\n
“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.”<\/p>\n
Before this can happen, however, it’s important to understand how else\u00a0fmo-2\u00a0affects organisms.<\/p>\n
In another study, published in\u00a0Science Advances, the team demonstrated that the enzyme affects behavior in noticeable ways.<\/p>\n
Worms engineered to overexpress fmo-2 were apathetic to positive and negative changes in their environment: they did not flee from potentially harmful bacteria and when presented with food, didn’t slow to eat after a brief fast the way normal worms did.<\/p>\n
Worms engineered to completely lack fmo-2 also explored their environments less often than normal worms did. Both behavioral states, they found, were caused by a change in tryptophan metabolism.<\/p>\n
“There are going to be side effects to any intervention to extend life\u2013and we think one of the side effects will be behavioral,” said Leiser.<\/p>\n
“By understanding this pathway, we could potentially provide supplements to offset some of these negative behavioral effects.”<\/p>\n
Leiser plans to continue to study the connection between the brain, metabolism, behavior and health with the hopes of contributing to the development of drugs to target these innate pathways.<\/p>\n
“Investigating all of the individual signals that our brain is responding to from the gut is a hot but not well understood area.”<\/p>\n
Source:<\/p>\n