Biologists at Brown University have found that a neuropeptide hormone produced in the guts of flies can influence their lifespan. This research, published in PNAS, could also have implications for humans, especially as new diabetes and obesity medications based on similar gut hormones become more common.
Marc Tatar, a professor of biology at Brown University, has studied the role of insulin and insulin-like growth factors (IGFs) in aging in flies for the past two decades. “Reducing insulin and IGF signaling slows aging and extends lifespan in flies,” Tatar explained.
Tatar’s research takes an ecological and evolutionary approach. His lab has been examining an insulin-regulatory hormone in flies called neuropeptide F (NPF). This hormone is produced in the gut and released into the bloodstream in response to diet.
In their recent study, the researchers used genetic tools to reduce the secretion of NPF from fly intestines. This also decreased insulin secretion. They traced the production of NPF from the gut to the brain and connected it to diet.
They found that reducing gut NPF increased lifespan in flies. The same effect was observed when they blocked NPF receptors in the brain, which influence another hormone called juvenile hormone. The study concluded that gut NPF regulates aging by integrating nutrient sensing, insulin signaling, and juvenile hormone production.
“We showed how these factors work together to control lifespan,” Tatar said. The team is now exploring what happens when they increase NPF secretion and, consequently, insulin levels in flies. “We suspect that overproduction of gut NPF will negatively affect aging and shorten lifespan,” he added.
Despite their simplicity, flies share many genes with humans. While humans don’t produce NPF or juvenile hormone, they do produce insulin and gut hormones that regulate insulin production, like pancreatic polypeptide Y (PPY) and glucagon-like peptide-1 (GLP-1). GLP-1 is in the same hormone family as NPF and can increase insulin secretion.
Research on GLP-1 agonists, which mimic GLP-1 in humans, has surged. These drugs trigger insulin release from the pancreas. Tatar’s team believes that since insulin-boosting drugs like GLP-1 agonists are used to treat diabetes and obesity, it’s worth considering their potential effects on human aging.
“The fly is an excellent model for humans, but we need to move from flies to mice to study GLP-1 agonists and aging,” Tatar said. “It will take years, but it’s important.”
The research received funding from the National Institutes of Health and the Czech Science Foundation.
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