Help us: Donate
Follow us on:

Smelling Food Undermines Dietary Restriction in Nematodes

The smell of food is enough to reduce the lifespan gains from dietary restriction in nematodes.

Smell of FoodSmell of Food

Experiments by researchers in China and the US have shown that the smell of food is enough to reduce the lifespan gains caused by dietary restriction in nematodes. By unraveling the genetic and neurological network behind this, the team found evidence that the same might hold true in mammals.

Dietary restriction is more than a diet

Dietary restriction is one of the most effective longevity interventions, increasing lifespan and improving health in a wide range of creatures, including yeast, fruit flies, mice and primates. While there is no conclusive evidence that dietary restriction increases human lifespan, many people experiment with caloric restriction or intermittent fasting because of the expected health benefits.

Despite the widespread effectiveness of dietary restriction, the mechanisms linking it with health and longevity still aren’t fully understood. The nutrient signaling pathways involving AMPK and mTOR are clearly involved, but other interacting pathways or players in the process remain to be discovered. There is evidence that non-nutrient components of food can also affect aging. For example, a 2007 study showed that “nutrient-derived” smells can affect lifespan and block the benefits of dietary restriction in fruit flies [1] .

The power of smell

In the new study, researchers grew C. elegans nematodes in petri dishes with and without bacteria, which is what they eat. Some of the plates also had a thin layer of bacteria on the lid, so the nematodes could smell them but couldn’t eat them. This had no effect on lifespan for the nematodes with free access to bacteria, but in the dishes without bacteria, it caused a 50% decrease in the longevity gain from dietary restriction. In a nutshell, the smell of bacteria offset some of the lifespan extension caused by dietary restriction.

The team then carried out a series of experiments using loss-of-function mutants, neuron activity measurements, and cell-specific depletion or overexpression of genes, which allowed them to piece together the neural circuit involved. The signal is carried through a sequence of neurons from the brain to the intestine – interfering with any of the neurons in the link blocked the effect of the food smell – and is mediated by the neurotransmitter octopamine, which is the invertebrate homolog of norepinephrine. Octopamine affects lifespan by regulating the energy sensor AMPK In the intestine.

There are more details about the pathway in the study, but the most interesting point is that the researchers tested whether this signaling link is also present in mammals. They studied cultures of mouse cells that are functionally similar to the nematode intestine and showed that norepinephrine activates AMPK via the same signaling pathway. Whether this is linked via neurons to the perception of smells remains an open question, let alone whether that could alter the longevity benefit of dietary restriction.

The role of food nutrients in mediating the positive effect of dietary restriction (DR) on longevity has been extensively characterized, but how non-nutrient food components regulate lifespan is not well understood. Here, we show that food-associated odors shorten the lifespan of Caenorhabditis elegans under DR but not those fed ad libitum, revealing a specific effect of food odors on DR-mediated longevity. Food odors act on a neural circuit comprising the sensory neurons ADF and CEP, and the interneuron RIC. This olfactory circuit signals the gut to suppress DR-mediated longevity via octopamine, the mammalian homolog of norepinephrine, by regulating the energy sensor AMP-activated protein kinase (AMPK) through a Gq-phospholipase Cβ-CaMKK-dependent mechanism. In mouse primary cells, we find that norepinephrine signaling regulates AMPK through a similar mechanism. Our results identify a brain–gut axis that regulates DR-mediated longevity by relaying olfactory information about food abundance from the brain to the gut.


This is a great example of the value of basic research. C. elegans is a tractable system for investigating this kind of question, and it’s well-characterized enough that the researchers could tease apart all the many components linking food scents with lifespan. That would have been incredibly difficult – if at all possible – in a model mammal system, let alone in humans. The team then built on that to show that the same thing could happen in mammals, opening the door to lots of interesting questions and experiments. For example, which odors are important? What about other sense modalities, like sight? While we’re a long way from being able to say that the same thing happens in humans, the idea that lifespan could be extended by manipulating the perception of food is certainly appealing.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

New Way to Help Aging Cells Produce Collagen

Scientists have demonstrated that extracellular vesicles loaded with mRNA coding for collagen production can be easily produced and delivered into...

Brain Aging on a Small, Physical Level

A new publication in Nature Aging has explained a great deal about aging of the neurovascular system, showing where and...

Eric Verdin on the Buck, Nutrition, and Ketosis

Six years ago, Dr. Eric Verdin, already a highly acclaimed veteran geroscientist, was catapulted to the forefront of the field...

New Year, Same Goal to End Age-Related Diseases

The new year is well underway, and we have been our usual busy selves. Join us for the first editorial...


[1] Libert, S. et al. Regulation of Drosophila life span by olfaction and food-derived odors. Science (2007), doi: 10.1126/science.1136610
About the author
Sedeer el-Showk

Sedeer el-Showk

Sedeer became a professional science writer after finishing a degree in biology. He also writes poetry and sff, and somehow juggles an ever-growing list of hobbies from programming to knitting to gardening. Eternal curiosity and good fortune have taken him to many parts of the world, but he’s settled in Helsinki, Finland for the moment. He hopes he’ll never stop learning new things.
No Comments
Write a comment:


Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.