A Genetic Clue to Why Stress Makes People Sleepy

This evolutionarily perplexing behavior could help repair damaged DNA.

From an evolutionary perspective, you’d think stressful experiences would require high alertness. But sometimes, stress means going to sleep.

One relevant situation you’ve probably experienced—and that you share with a lot of the animal kingdom—is the overwhelming snooziness that comes with fighting off an infection. In some creatures, even overheating triggers a nap. And for certain people, the stress of an argument can send them to slumberland, a take on “fight or flight” that seems to make little sense in terms of survival.

Scientists have studied such stress-induced sleep, which is different from the circadian sleep we indulge in every night, in rabbits, mice, and even roundworms, in search of an explanation for why this happens. Now, a new paper in the journal Genetics reports an intriguing finding: A gene that helps repair damaged DNA is involved in putting roundworms under when they are stressed. This implies that at least during some types of stress-induced sleep, the body may be patching up its genes.

In the experiments, a group at the University of Pennsylvania exposed the roundworms to ultraviolet radiation, or UV. They were inspired to try a form of radiation because they had learned that radiation therapy makes patients tired, says Hilary DeBardeleben, a visiting professor at La Salle University who performed the work when she was a postdoc in the lab of David Raizen. Indeed, a dose of UV put the worms to sleep for a couple hours.

UV is the radiation behind sunburns and mutations that increase the risk of skin cancer: Enough insults in enough genes, and the constraints on cells’ growth relax, leading to cancer. Given this connection between UV and genetic damage, the researchers wondered whether p53, a protein of some fame in cell-biology circles for its connection to DNA repair, might be involved in the worms’ wooziness. The protein does a lot of things, but it’s most known for guarding against cancer by patrolling an organism’s DNA, checking for errors, and organizing fixes.

“The reason it’s so famous,” says DeBardeleben, “is that if you have a mutant in the p53 gene, the cancer-surveillance system doesn’t work as well,” leaving an organism vulnerable to future damage. Mutations in p53 have been found in all kinds of cancers, including lung, breast, and colon cancer.

DeBardeleben and her colleagues looked at whether shutting down the gene that produces p53 changed their worms’ response to a dose of UV radiation. And curiously enough, it did: “If you knocked out p53, they slept less,” she says. That made the researchers sit up a little straighter. Maybe p53 was alerting cells that sense stress, which would then do the work of turning down the nervous system and putting worms under, for whatever restoration sleep might provide.

But that turned out not to be true. Further experiments made it clear that the only place where p53 levels matter, with regard to stress-induced sleep, is in the worms’ neurons themselves. It is doing something in there, after worms are hit by UV radiation, that encourages this somnolent response. Is this in aid of DNA repair, somehow? And why would sleep be needed for repair, anyway? “It is likely that DNA is being repaired while the worms sleep, but I can’t know for sure,” DeBardeleben says.

While the researchers were not able to get much clarity, this connection between DNA damage and stress-induced sleep is still a new angle on the behavior’s origins. Other groups have found that some kinds of stress-induced sleep are required to refurbish proteins that have been warped by heat. That does not appear to be the case in these worms, as their proteins are intact; something else must be happening.

In a way, the fact that there may be many different explanations for stress-induced sleep isn’t surprising. The triggers are so varied, from a sunburn to a tense email exchange, that what happens to look like the same behavior to us might actually be a variety of different responses, with different roles to play. “There are a lot of types of damage that can occur to a cell upstream that all seem to converge on this one behavioral outcome,” reflects DeBardeleben, “which is sleep.”