byNagoya University

C. elegans roundworms engineered with fluorescent proteins to visualize neurons. Credit: Noma lab, Nagoya University

When roundworms stop reproducing, they can still move and function normally but lose their ability to detect certain food odors that once led them to their meals.

Researchers at Nagoya University have found the gene that causes this sensory decline. Published inAging Cell, this is believed to be the first time scientists have identified a gene that actively shuts down food-odor detection in aging animals.

For decades, scientists believed that aging happened mainly through accumulated damage. The idea that genes actively program specific decline rather than gradual deterioration is relatively new and controversial. Since similar genes exist in mammals, scientists can now study if they cause age-related decline in other animals, including humans.

Caenorhabditis elegans is a microscopic roundworm about one millimeter long that lives for only two to three weeks. These transparent worms reach adulthood in three days, reproduce for several days, and then age and die naturally. Their short lifespan allows scientists to study aging processes in weeks rather than years.

"Day five is right after roundworms finish reproducing and have already passed their genes to the next generation. At this time, these worms normally experience a sharp decline in their ability to sense diacetyl, an odor released by their bacterial food source," Kentaro Noma, senior author and associate professor at Nagoya University Graduate School of Science, said.

The researchers created worms with random genetic mutations. When they tested them on day five, most had lost their ability to smell food, just like normal worms. However, some mutants kept this ability. These worms had a mutation in the nhr-76 gene which showed that this gene causes the decline in smell.

"nhr-76 produces a protein that switches off the genes responsible for detecting food odors. It works directly in the sensory neurons responsible for smell," lead author and graduate student Rikuou Yokosawa explained. "The protein may receive a chemical signal to work, which suggests something in the aging body activates it."

Why does this harmful gene exist? There are two possibilities. Either natural selection simply cannot remove it because it acts after reproduction, or it actively evolved because the decline benefits the population by reducing competition for resources.

Evolution works by getting rid of genes that prevent organisms from reproducing. But once reproduction happens, any genes, even harmful ones, have already been passed to the next generation. This is why genes that cause decline after reproduction can persist; their negative effects appear too late for evolution to remove them.

However, the researchers propose a different explanation. The decline in food-seeking behavior after reproduction ends could benefit the population by reducing competition between older and younger animals for resources. If true, this active genetic program may have evolved to help offspring survive in a competitive environment.

While most aging research has focused on how damage accumulates over time, this study identifies a gene that actively causes a specific behavioral decline in roundworms. Whether similar programmed mechanisms contribute to human aging remains an open question.

"Similar genes (nuclear hormone receptors) exist in mammals, and there are hints they might play related roles in aging, but no clear parallel finding has been established in humans or other mammals yet. This is why this study is important; it provides a model that could guide future research in other species," Professor Noma notes.

More information Rikuou Yokosawa et al, A Nuclear Hormone Receptor nhr‐76 Induces Age‐Dependent Chemotaxis Decline in C. elegans, Aging Cell (2025). DOI: 10.1111/acel.70277 Journal information: Aging Cell