Reduced protein intake is correlated with longer lifespans in animals, but the reasons why have eluded researchers.
A new study published in the journal PNAS offers insights into the biological mechanism behind this connection. Using fruit flies, researchers found that the suppression of a gut hormone called Neuropeptide F, or NPF, resulted in longer lifespans.
“Our study indicates that Neuropeptide F, which has been known for its role in the brain, can also act in the gut to influence aging via interacting with insulin and juvenile hormone pathways,” wrote Jiangtian Chen, a senior research associate at Brown and the study’s primary author, in an email to The Herald.
NPF’s role in aging is part of a multi-step process, Tatar said. When protein is consumed, it is detected by the gut and triggers the secretion of NPF, increasing insulin production. This increase in insulin controls aging through a tissue called the corpora allata, which produces the juvenile hormone that ultimately controls lifespan.
“If we block (NPF) receptors on the insulin-producing cells, the flies make less insulin, and then they’re long-lived,” said Marc Tatar, professor of biology and a co-author of the study..
In addition to blocking insulin production, researchers also inhibited insulin at the corpora allata to control aging. By blocking these two stages of the insulin regulation process, researchers were able to extend the flies’ lifespan.
The study was a years-long affair, starting before the COVID-19 pandemic. Building the precise genetic tools needed to carry out the experiment was a tall task.
“A big problem is that these hormones that are made in the gut — both of humans and in the fly — are also made in the brain,” Tatar said. “It took us 18 months or two years, almost, to work out the genetic tools we needed so that we can manipulate the NPF in the gut without affecting the NPF in the brain.”
Researchers also had to develop tools to directly quantify NPF levels in the flies, Chen said. Since Drosophila fruit flies don’t have closed blood systems, researchers couldn’t predict the amount of NPF by measuring its secretion in blood.
The study has valuable implications for human models and opens up new avenues for research, according to both Chen and Tatar.
Tatar expressed interest in the gut microbiome and how diet can affect neuropeptides like NPF. He hoped that future research would make it possible to customize “diets or microbiome compliments” to bolster health using non-drug methods.
Chen explained that by examining the mechanisms of chemical signals in the gut, researchers can utilize these findings to influence health and aging.
“We work with Drosophila as a model organism,” Chen wrote, “but we hope our findings will eventually translate to human health, potentially contributing to ways of extending the human health span.”
