The identification of a pathway regulating communication between the gut and brain in fruit flies highlights the need to further explore how certain medications, particularly GLP-1 agonists, can be utilized to combat obesity and diabetes in humans.
A research team at Brown University has found that a neuropeptide hormone produced in the gut of fruit flies plays a significant role in managing their lifespan.
This research, shared in PNAS, the scientists suggest, has potential implications for human health—especially since new medications targeting diabetes and obesity that focus on gut hormones, similar to those found in flies, are gaining popularity.
For the last 20 years, Marc Tatar, a biology professor linked with the Center on the Biology of Aging at Brown University, has been investigating how hormones like insulin and insulin-like growth factors (IGFs) influence aging in fruit flies.
“Reducing insulin and IGF signaling is known to slow aging and prolong life in flies,” stated Tatar.
Tatar’s study of aging incorporates perspectives from ecology and evolutionary biology, reflecting the interdisciplinary nature of the Center on the Biology of Aging. His team has been examining a hormone called neuropeptide F (NPF) in flies, which is produced in the gut and released into the bloodstream in response to dietary intake.
In their study published in PNAS, they developed genetic techniques to lower the capacity of fly intestines to produce NPF, consequently diminishing insulin release. They then traced the movement of NPF from the gut to the brain and linked it to the nutritional intake of the flies.
The researchers discovered that decreasing gut NPF led to increased lifespans in flies. Similarly, blocking NPF receptors in the brain, which influences another hormone known as juvenile hormone, also extended longevity. They concluded that gut NPF plays a role in modulating the aging process in flies by integrating nutrient assessment, insulin signaling, and the production of juvenile hormone.
“We demonstrated how these mechanisms interact to regulate lifespan,” Tatar explained.
Currently, the research team is running further tests to observe the effects of heightening NPF secretion and, as a result, raising insulin levels in flies.
“According to our findings in PNAS, we believe that excessive production of gut NPF in flies could negatively influence aging and shorten lifespan,” added Tatar.
Despite being small and simple organisms, Tatar points out that fruit flies share many genetic similarities with humans, and there are corresponding hormones in humans that perform similar functions. Gaining insight into aging processes in flies may give us valuable information regarding human aging as well.
While humans do not produce NPF or juvenile hormone, they do produce insulin and secrete gut hormones that influence insulin levels, like pancreatic polypeptide Y (PPY) and glucagon-like peptide-1 (GLP-1). GLP-1 is part of the same hormonal family as NPF; both are called incretins since they can stimulate insulin release.
Research into GLP-1 agonists, which imitate GLP-1 in humans and prompt insulin release from the pancreas, has surged in recent years.
Tatar’s research group concluded that considering the role of insulin-enhancing medications like GLP-1 agonists in managing diabetes and obesity, along with their findings about the correlation between insulin and aging in flies, it may be essential to investigate their effects on human aging.
“Fruit flies are an excellent model for human biology, but we need to extend this research to mice and design studies that investigate GLP-1 agonists in relation to aging,” Tatar stated. “It will require time, but it is a crucial step forward.”
This research was supported by funding from the National Institutes of Health (R01AG059563, R37 AG024360, R21AI167849) and the Czech Science Foundation.
