Elderly Mice's Brains Are Bad at Handling Jet Lag

… and could help explain why humans have so many sleep disruptions later in life.

Four mice sleeping in a nest
Joe McDonald / Getty

Strange things happen to sleep as the body ages. For humans, getting older can mean waking up over and over again or shifting to a much earlier wake-up time. In elderly mice, the region in the brain that directs the circadian clock—the suprachiasmatic nucleus—can go off the rails, as the 10,000 cells that make it up, which normally fire all together, lose touch and fall out of sync.

In a new set of experiments published in the journal Neurobiology of Aging, researchers put young and old mice through a battery of tests to compare their responses to jet lag. They found that elderly mice are far less flexible than young mice, and the reason appears to lie in a particular deficit in the brain as they age.

The circadian clock is reset by light. When we open our eyes after sleeping, the sun activates the suprachiasmatic nucleus and the clock starts over again. Leave mice—or, for that matter, people—in the dark, and at first, they’ll get up and go to sleep at roughly the same time as usual. But let it go long enough and their days will start to get longer, as their internal clock drifts without any external signals from the sun.

In these new experiments, Gurprit Lall, a professor of pharmacology at the University of Kent, and colleagues kept young mice and old mice in the dark for 10 days, recording the hours both groups spent on their exercise wheels to keep track of when they were awake. Then the researchers exposed the mice to 15 minutes of light, setting their clocks ahead as if they’d just gotten off a plane. The young mice responded easily, and adjusted their period of activity later by an hour. The older mice, however, responded much less, moving only about half an hour.

The researchers checked to see whether the older mice had cataracts or some other eye defect keeping light from getting through, but that was not the case. “If the eye is okay, but we’re still seeing this difference, what could be driving it?” asks Lall. He and his colleagues looked at how the message of light’s arrival is received in the brain. When they started probing why it might not be making it to the suprachiasmatic nucleus, or at least not as clearly as in young mice, they discovered a problem with a neurotransmitter that delivers it.

When glutamate, this neurotransmitter, arrives in the suprachiasmatic nucleus, it attaches to a protein on the surface of brain cells and triggers a series of events that result in the clock being reset. The researchers squirted a substance that clings to this protein receptor, mimicking the effect of glutamate, to the suprachiasmatic nuclei of both young and old mice. It reset their clocks, just as if they’d been exposed to light. But the old mice still lagged behind the young. They just were not as sensitive to the chemical message for some reason.

The receptor is made up of a few different parts, which snap together like Lego pieces. The researchers found that one part, in particular, was made far less in older mice than in young mice. When they artificially decreased the amount of this part in young mice, suddenly, the young mice responded to light as if they were old. This result suggests that elderly mice respond less flexibly to jet lag because these receptors in their brains lack this particular piece. Without that bit in play, the receptor seems to behave differently, and the effect is that the circadian clock is no longer working as well.

“We don’t really know why that happens,” says Lall. And it is not clear exactly how this work translates to the common human experience of fragmented, disturbed sleep as we age. But it’s an intriguing clue that we might actually be able to pick apart, at the level of individual proteins and neurotransmitters, the reasons why the clock responds differently to light over the course of a lifetime.