Iowa State researchers find key factor linking longer maturation to longer life in fruit flies

AMES, Iowa – Biologists know that animals that mature slowly tend to live longer, but they aren’t sure why. A recent study of fruit flies by an Iowa State University research team sheds new light on the link between developmental timing and longevity, which could lead to a better understanding of how to lengthen human lives.

The study, published this month in the Proceedings of the National Academy of Sciences, found that fruit flies missing a crucial developmental hormone, PTTH, enter the pupal stage about a day later than usual and subsequently end up living up to 30% longer. This elongated life is marked by reduced inflammaging, the chronic inflammation associated with aging.

“Their increase in inflammation is much slower as they age,” said the paper’s lead author, Ping Kang, adjunct assistant professor of genetics, development and cell biology. “It’s a robust difference. Every time we repeated it, they lived longer.”

Comparing RNA expression of standard fruit flies and no-PTTH flies connected the reduced adult inflammation in the longer-living mutants to a signaling pathway, NF-kB, that plays a crucial role in the immune responses animals use to fend off pathogens. Gene knockout experiments showed that the enhanced longevity only came when NF-kB was silenced during the larva-to-adult transition and within the flies’ liver-like oenocyte cells.  

Model to build on

The researchers found that the flies without PTTH were still able to fight off a bacterial pathogen, despite the diminished immunity signaling during development. They also maintained the growth rate of a typical fly, which was of interest because it can be difficult to separate the life-extending effects of slower maturation from the slower growth rate that often comes with it.

“Development time and growth rate are two different but related concepts. This evidence decouples them and suggests developmental timing is more important for longevity,” said study co-author Hua Bai, associate professor of genetics, development and cell biology.  

The connection between developmental timing and lifespan in fruit flies could be a useful model for studying the dynamic in humans, Bai said. While there is no directly comparable growth hormone to PTTH in mammals, other hormones could have a similar effect via immunity signaling.

“If we understand the fundamental mechanism, it may be possible to manipulate it,” he said.

Hands-on learning

The study’s 18 co-authors include six Iowa State undergraduates, who are a common sight in Kang and Bai’s labs. They teach one of the sections of Biology 1140X, a one-credit course designed to give first- and second-year students hands-on research experience. Working with fruit flies is an ideal fit for undergraduate researchers because the flies are inexpensive, easy to handle and short-lived.

“Most students are so intimidated at first. They don’t want to screw up. But I always tell them don’t worry, we’ll start over if they die,” Kang said.

Five of the undergraduate contributors to the study primarily helped document the flies’ lifespans. Wren Murzyn, a senior in genetics from Fort Collins, Colorado, developed a protocol for peeling off a fly’s pupa case to dissect the oenocyte tissue.

It took trial and error, consistent practice, careful observation and detailed note-taking to establish the dissection method, said Murzyn, who has worked in Kang’s lab as a research assistant since taking 1140X in fall 2022. The importance of patience and persistence was a major takeaway from her lab work at Iowa State, a lesson in perseverance she hopes to apply after she finishes her bachelor’s degree this fall and continues on to graduate school.

“Pushing forward, repeating experiments and refining techniques are all part of the process. The more effort and repetition you invest, the more you learn and improve, and the more rewarding the results become,” she said.