Hungry laboratory animals tend to live longer. Over and over, in organisms ranging from fruit flies to mice (and sometimes even in primates), scientists have seen that cutting back on food extends their study subjects’ life span. But do wild animals also benefit from eating less? And if so, why? Some scientists are trying to move their experiments beyond typical lab conditions to answer these questions.
Decades ago scientists suggested that hungry animals shift their energy from reproducing to maintaining their body to increase the chance that they’ll live through the period of famine and reproduce when times get better. The theory became known as the adaptive resource reallocation hypothesis.
For some scientists, this explanation never seemed to add up. Wild animals contend with constant threats, including pathogens, weather and competitors. Delaying reproduction doesn’t make sense when life is so fraught. A hungry animal, moreover, will take more risks to find food, which will likely result in its earlier demise. “It’s almost ludicrous to think that animals in the wild that are dietarily restricted are healthier or live longer,” says evolutionary biologist Steven Austad of the University of Alabama at Birmingham.
In a recent preprint study, evolutionary biologists Felix Zajitschek and Russell Bonduriansky, both at the University of New South Wales in Australia, and their colleagues set about to investigate these questions by attempting to replicate what happens to an animal when calorie intake drops outside the confines of the lab. They kept fruit flies a few degrees below their optimal temperature to simulate a moderate stress that these animals might encounter in the wild. Chilly females that were kept on a restricted diet started dying after only about 20 days, whereas many of the flies that were fed a normal amount lived for 100 days or longer. Even Zajitschek was surprised by how quickly the flies dropped off when he deviated from normal lab conditions. “To be honest, I didn’t expect such a strong effect,” he says.
The researchers’ work has yet to be peer-reviewed, and some scientists think it’s premature to say that the longevity associated with dietary restriction is a lab artifact, as the preprint study suggests. “To go from there to state that everything people did before is artificial is a big step,” says aging expert Maria Ermolaeva of the Leibniz Institute on Aging–Fritz Lipmann Institute in Germany. Biologist Mirre Simons of the University of Sheffield in England agrees. “It shouldn’t be overinterpreted,” he adds.
There’s reason, though, to think Zajitschek and his colleagues might be onto something. Other researchers have supplemented the diets of wild animals to answer tangential questions, Austad says, and “they never live shorter.” For example, researchers have given wild birds extra food to see how it shapes their communities and predation habits. The animals tend to either live the same length of time and reproduce more when their diet is supplemented or live longer, he adds.
In 2006 Austad and his colleagues published the results of their own foray into addressing this conundrum: They captured wild mice, then fed their grandoffspring restricted diets in the lab to see if they’d react the same as strains reared in the lab for many generations. Whether the descendants of wild mice ate a lot or a little, their survival was about the same on average. Austad wasn’t surprised: lab mice have lived in captivity for so long that comparing them to their wild counterparts is “like Yorkshire terriers compared to wolves,” he says.
Studying dietary restriction in a truly wild setting is very challenging because scientists can’t stop wild animals from seeking out food when they get hungry. Instead Bonduriansky and his colleagues tried supplementing the diets of wild antler flies. These flies—with a body about a tenth of an inch long—spend their entire lives living on a single discarded antler from an animal such as a moose or a deer. The team marked flies with tiny drops of enamel paint to make them recognizable, then periodically captured the marked flies, fed them extra sugar or protein in glass vials and released them back to the wild or kept them in the lab.
Some trials suggested that flies kept outdoors lived just as long when they ate extra food as their hungrier outdoor counterparts—contrary to what tends to happen in the lab. But the experiments were often interrupted, for example, when spiders ate their study subjects. “It wasn’t possible to get a really robust answer,” Bonduriansky says, but the results gave him hope that with a bit more fine-tuning, robust studies in the wild will be possible.
In 2020 Simons and his colleagues published the results of a study that tested the adaptive resource reallocation hypothesis directly. The researchers predicted that if hungry flies put more energy into taking care of their body than did their counterparts on a rich diet, then the hungry flies would fare better when they were returned to a rich diet than those who were fed a rich diet continuously. In fact, the team found the opposite: flies that alternated between rich and restricted diets had higher mortality rates than flies that ate a rich diet the entire time. The experiment is one reason Simons says the adaptive resource reallocation hypothesis, “for me, is quite out the window.”
Instead lab animals might live longer when their diet is restricted because something they’re eating—or something their body produces after they eat—is intrinsically toxic, so eating less means reducing the toxicity, Simons says. Which dietary component is toxic is currently unclear, he adds, and it may vary for different situations. Austad has another theory: he thinks hungry wild animals will be likely to start eating nonideal food sources, such as fungus-covered grain, some of which might be toxic. Hungry animals might turn on cellular pathways that protect against toxins. These same pathways could protect animals from toxins that the body produces as a by-product of metabolism, which could contribute to aging.
As for why lab animals and wild animals might react to dietary restriction differently, Simons thinks the issue could be that different amounts of dietary restriction work best in different conditions. For example, a mouse with a running wheel might not benefit from as restricted a diet as a mouse that’s just sitting around. An animal’s individual genetic makeup and its sex might also influence how much dietary restriction is optimal. “You need to titrate,” he says.
Some people adhere to a restricted diet with the hope of living longer or deriving other health benefits. Zajitschek and Ermolaeva, for example, both subscribe to intermittent fasting regimes, which involve alternating periods of unrestricted eating with periods of fasting. It’s unclear whether these practices extend life span for humans, although they may bring other benefits such as helping maintain a healthy weight or lowering blood pressure. Biogerontologist Mark Mc Auley of the University of Chester in England warns that anyone thinking of starting a restricted diet should be cautious. People vary in all sorts of ways. The degree of dietary restriction that’s right for one person might not work for another. And in general, studies on dietary restriction have left Mc Auley with “a lot more questions than answers,” he says.
To flesh out their understanding of this practice, Mc Auley thinks scientists need to find a new balance between the lab and the field. For example, scientists recently studied how fruit flies adapted to environmental changes when they were kept in mesh enclosures in a Pennsylvania peach orchard. Mc Auley wonders if scientists could study dietary restriction in insects or other animals using similarly controlled outdoor settings. One way or another, “we definitely need to look at this in the wild,” he says.