Fly Hormone Discovery Sheds Light on Lifespan Regulation and Aging

Researchers at Brown University have found that a neuropeptide hormone produced in the gut of flies influences their lifespan.

The study, published in the journal PNAS, has potential implications for humans, particularly as new diabetes and obesity treatments based on gut hormones related to the fly hormone are being developed.

For the past two decades, Study Author Marc Tatar, a Biology Professor affiliated with the Center on the Biology of Aging at Brown University, has investigated how insulin and insulin-like growth factors (IGFs) affect aging in flies.

We know that reducing insulin, and reducing IGF signaling, slows aging and extends lifespan in flies.”

Marc Tatar, Study Author and Professor, Brown University

Scientists at the Center on the Biology of Aging, led by Tatar, examine aging from an ecological and evolutionary perspective. Tatar's lab has been studying neuropeptide F (NPF), an insulin-regulatory hormone in flies that is produced in the gut and secreted in response to diet.

The researchers used genetic tools to impair the ability of fly intestines to secrete NPF, thereby reducing insulin secretion. They mapped NPF production from the gut to the brain via a pituitary-like tissue and linked it to diet.

The study found that suppressing gut NPF and blocking NPF receptors in the brain that control juvenile hormones both extend fly lifespan. The researchers concluded that gut NPF influences aging in flies by integrating nutrient sensing, insulin signaling, and juvenile hormone production.

“We showed how all of these things work together to control lifespan,” Tatar said.

They are conducting further experiments to investigate the effects of elevated NPF secretion and resulting insulin levels in flies.

Based on this research reported in PNAS, we suspect that over-production of gut NPF in flies will have a negative effect on aging and decrease lifespan.”

Marc Tatar, Study Author and Professor, Brown University

Tatar said that despite their small and simple nature, flies share many genes with humans. They also have analogous hormones involved in similar processes and pathways. Studying aging mechanisms in flies may provide insights into what happens in humans.

Humans do not produce NPF or juvenile hormones. However, they do produce insulin and secrete gut hormones that regulate insulin production, such as PPY and GLP-1. GLP-1 is an incretin hormone, like NPF, as it increases insulin secretion.

Research on GLP-1 agonists, which mimic the incretin GLP-1 in humans and stimulate insulin release in the pancreas, has grown significantly.

Tatar's research team found that insulin-increasing drugs like GLP-1 agonists, used to treat diabetes and obesity, may also have implications for human aging based on their findings about insulin and aging.

The fly is an excellent model for humans, but we need to progress the research from flies to mice and set up studies that look at GLP1-agonists and aging. It will take years, but it is important.”

Marc Tatar, Study Author and Professor, Brown University