Key Takeaways
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When HHMI Investigator Amita Sehgal started studying sleep 25 years ago, the topic elicited a yawn from most biologists.
“In the year 2000, if I had suggested to my department that we hire people working on sleep, they would have laughed at me,” says Sehgal, a molecular biologist and neuroscientist at the University of Pennsylvania. “The thinking was that sleep is not something that neuroscientists do; psychologists study sleep and dreams.”
Now, more than two decades later, sleep science has finally woken up.
Biologists around the world are now studying sleep in everything from fruit flies to jellyfish to understand the fundamental molecular and cellular mechanisms that drive slumber and answer the age-old question of why we sleep.
“Sleep is widely conserved across the animal kingdom and so it must have some basic function that is the same across species, and so what is that?” Sehgal says. “We’re finally getting to a point where we are recognizing a few basic principles about sleep.”
Sleep Keeps the Brain’s Powerhouses Healthy
Sehgal and her team were among the first to use fruit flies to study the cellular and molecular processes driving the need to sleep.
The team’s recent research suggests that the drivers of sleep are metabolic and that sleep plays a key role in protecting the integrity of mitochondria — the structures that power brain cells.
When we are awake, our neurons are constantly firing, powered by the energy produced by mitochondria. A byproduct of this energy production is reactive oxygen species, which can cause damage to the mitochondria and the cells that house them.
Sehgal and her team found that sleep helps neurons stay healthy by facilitating the movement of this oxidative damage to glia cells — a type of supporting cell in the brain — in the form of oxidized lipids. The glia break down some of these lipids to generate energy. They also pass along some of the lipids to blood cells, which have specific receptors to receive them.
“You need those neurons to be functional, and for them to functional, they need a reliable internal source of clean energy,” Sehgal says. “One of the ways that sleep is helping the neurons stay healthy is by moving these lipids along to remove some of the oxidative damage.”
Sleep is a Cellular Housekeeper
In addition to these findings, other recent research by Sehgal and her team shows:
These findings all support the team’s hypothesis that sleep is driven by metabolic needs. When we don’t sleep, metabolic waste builds up in the brain, meaning neurons — and the energy-generating neuronal mitochondria — can’t function properly.
“We are super excited about our research right now,” Sehgal says. “We feel like we’re sort of really starting to crack the whole sleep thing.”
A Link to Neurodegeneration
The team’s findings on sleep regulation could help researchers better understand neurodegenerative diseases like Alzheimer’s, which are commonly associated with disordered sleep.
Two processes that Sehgal’s lab has shown are regulated by sleep — lipid metabolism and autophagy — are also known to contribute to neurodegeneration when they go awry, and both are disrupted in patients with Alzheimer’s disease.
In flies, the team found that damage is transferred from neurons to glial cells via lipid carriers similar to apolipoprotein E (APOE). In humans, a form of APOE that increases Alzheimer’s risk is less effective at transferring lipids from neurons to glia, suggesting a possible link.
Understanding how sleep influences these cellular processes could help shed light on how their disruption also contributes to Alzheimer’s disease.
“In our very basic work on sleep, we're finding processes that are regulated by sleep, and that are relevant to and disrupted in Alzheimer's,” Sehgal says. “The sleep disruption in Alzheimer's could account for disruption of these two processes.”
Nature
Sleep-dependent clearance of brain lipids by peripheral blood cells
11-Feb-2026