The metabolic consequences of skipping sleep, and cuts and layoffs slam NIH
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This is the Science Podcast for April 11th, 2025. I'm Sarah Crespi. First up this week, Science Insider editor Jocelyn Kaiser joins us to discuss big changes in science funding and government jobs this month, including an order to cut billions in contracts and mass firings at the National Institutes of Health.

Next on the show, we're taking sleep more seriously. Researcher Jennifer Tudor talks about how skipping out on sleep has many metabolic consequences, from reducing protein synthesis in our brains to making our muscles less efficient at using ATP. And she suggests that given these impacts, we should stop putting sleep at the bottom of our to-do lists.

This week, we're checking back in with what's happening in the world of science policy and funding in the U.S. Insider editor Jocelyn Kaiser is here with an April update for us. A lot has already happened this month. We're talking on Tuesday, April 8th. Hi, Jocelyn. Welcome back to the podcast. Hey, Sarah. Let's go back to April 1st, April Fool's Day, actually. On this day, the Department of Health and Human Services, HHS, announced a large reduction in force

and removal of multiple heads of institutes at NIH. Can you describe the overall picture of what happened on that day? Sure. So the previous week, Department of Health and Human Services had said they were going to start laying people off.

But it was delayed for a couple days for some reason, and the notices didn't start going out really till April 1st to Tuesday early that morning. Although directors, several directors were notified the evening before that they were being removed from there, put on leave and reassigned. So that happened to four institute directors out of NIH's 27 institute directors and one acting director.

And then early on Tuesday, staff started getting their notices around 5 a.m. They started getting emails about who was, you know, people who were being tormented

terminated. And was there any pattern to these terminations? Yeah. So HHS has said it's all part of an effort to save money and make HHS run more efficiently. And they said that across HHS agencies, it would be administrative things like communications and acquisitions or purchasing at NIH, things like human resources and policy. And that is, as far as we know, most of the cuts that were made. But there were also

some scientists who received notices that they were being laid off, and there were entire offices who were doing something that is important for the function of that institute or that center who were laid off. The institute heads that were sent letters, they were kind of like reassignments. Where were they offered reassignments to? Yeah, it was kind of interesting. They were offered assignments with the Indian Health Service, which is like the health department

for, you know, at reservations, a lot of them way out west or...

Alaska. And the directors and other senior leaders at these agencies, they were being told they were being reassigned and offered a position with the Indian Health Service. And they had a couple of days to decide where they'd like to go. Meanwhile, they were put on leave. And although it's not stated in the notices they got, the implication is, you know, you have to accept this or you're out of a job. We saw some of this during the first Trump administration where they tried to move offices outside of D.C. so that people were kind of encouraged to quit instead of moving. Is that

what's going on here uh no i'd say it's pretty different because this is not saying we're going to move nih out of bethesda where the main campus is but that's maryland to kansas this is individuals being told you are leaving nih and you are going to another part of hhs and it you know probably has nothing to do with what you do know which is leading some big institute

Do we know why this was offered to them? Well, so we'd heard for some time that HHS Secretary Robert F. Kennedy Jr. was interested in removing institute directors at NIH, but we hadn't really seen that. Well, we've actually seen some of that already, but we don't know exactly why. These were the ones that were picked for this first, maybe the first round, but the National Institute of Allergy and Infectious Diseases said,

has been criticized by Republicans for their role in the COVID pandemic, in fighting the pandemic. And so it's not really a big surprise that they were on the list. Another institute that was law system director is the Minority Health Institute. And that potentially is because they do DEI kinds of related research.

Yeah. And why do they offer them transfer to a job at Indian Health Services? I don't know. There may be legal reasons why. I mean, we didn't write about it, but other people may have that this is a way to get people out of their positions without actually firing them. So we talked about NIH losing heads and then also firing staff. What about the other, you know, the other kind of well-known agencies under HHS, which is CDC and FDA? What happened there?

Yes, so at CDC, there were whole programs, divisions that were, virtually everybody was fired, like occupational health, HIV prevention, a lead poisoning prevention program. This is, among others, a gonorrhea testing program. And then at FDA, they lost the head of their office of new drugs, which we've

evaluates new drugs for safety and whether they work. And their tobacco center, I don't know the full list of FDA, but it was a lot of people. And they also lost, I think their entire communications office or just about. And they have a really important role in informing the public about safety issues with drugs and devices and drug recalls, things like that. And across all of these three units that we just talked about, thousands of people have been fired.

To me, it seems like that's going to mean a big slowdown in the work the FDA does approving drugs and medical devices and CDC's work keeping track of dangers to public health. I mean, are people worried about that?

Yeah, there's been some news stories about how the drug industry is not happy about this at all because they think it's going to slow down drug approvals and, you know, cutting inspections or staff is not good for them. At CDC, they're cutting, for example, HIV prevention programs. There's real concern that this is going to mean more HIV cases and infections.

This big reduction in force at HHS comes on top of some other big moves by the administration to cut these agencies way back, including a call to reduce contract spending by 35%. What are some of the possible ways that could actually happen in these organizations? I know most about NIH and

And at NIH, so a lot of many, many scientists and other staff there are actually contractors. In fact, I've read that something like, it's almost like a whole second staff, you know, the number almost as many as the federal employees who help run the place. Yeah, it's a huge group of people. Yeah, and I think it also reflects, you know, concerns in the past about the federal workforce getting too big. And so they started hiring contractors instead because they don't count in the numbers anymore.

So what I heard from talking to people is, you know, it's going to be brutal trying to find these cuts. They're going to have to cut a lot of staff, including scientists who help run labs. They may have to cut, and there's concern that there's a whole infrastructure for running clinical trials, and a lot of those people are contractors. And so I talked to someone who said they may have to

pause enrollment for ongoing trials, they may have to cancel planned trials. And this is both at NIH, which runs some clinical trials on its campus outside of Washington, and also at academic centers that are funded by NIH. Some of these big trials are funded through contracts. Okay.

Another thing that's going on is there's a lawsuit regarding the grants that have been canceled, federal grants to researchers, to institutions that have been withdrawn or canceled because of their association with specific topics like gender or diversity. That's been challenged in the courts. What's going on with that? So a couple of lawsuits were filed in just the last few days.

And I think these are the first that have directly challenged those grant cuts that were based on the executive orders from the Trump administration. It remains to be seen what will happen if there will be some sort of order from a judge

telling NIH that they have to restore those canceled grants. I've seen some of the firings that this administration has done have been challenged in court and people have been reinstated. Is that likely to happen here with what happened at HHS? Or are they hewing more closely to protocols for reducing the workforce?

So from what I know about that, the so-called probationary firings a few weeks ago, where people who'd been in their jobs just a year or two were fired, those were, I think maybe many of them or most of the illness agencies at court said this is illegal, and people were told they had their jobs back, although in some cases they weren't actually put back to work.

But this time, supposedly it's done in a more legal way, but I have read that there may be, it may be still possible to challenge it in court. Yeah. And then RFK said that even though these people are fired, there is a chance that some of them will have been mistakes and they will be rehired? Yeah. So, for example, HHS had said they were not going to fire. They said, you know, our plan is not to

to fire scientists, but they did. There were about 11 very senior scientists at the Neuroscientists Institute at NIH who were told they were being fired, including one researcher who was, you know, renowned and won a huge prize last year. They were told within a day or two that it was a mistake, maybe a coding error, and that they were going to get their jobs back. And yeah, and then also RFK Jr. said that some other things like the lead poisoning program

that they were going to bring that back and sort of a different part of HHS. He's creating some new department to advance his Make America Healthy Again agenda. Now, where's the head, the new head, the newly appointed head of NIH in all of this? So that is Jay Bhattacharya, who his first day was April 1st, which was the day of the riff. And he put out a note saying something like, I know this is going to be hard, but I love NIH and I'm going to

help us get through this and restore science or something like that. But of course, staff are wondering how meaningful that is considering that this happened under, you know, on his first day. So yeah, we don't really know exactly what his, I mean, he's laid out some priorities, but what he's going to do about

staff cuts or whether there's going to be further cuts, we don't really know. Okay. Is there anything else that we should pay attention to in the next couple weeks? I'll be watching to see what, as we said, the NIH director's first actions are beyond, you know, he did send an email telling staff they all need to use a consistent email signature in their emails.

which people were kind of disappointed by. And yeah, but I haven't heard of anything else that he's planning. Yeah, I mean, one little glimmer of good news at NIH is the council meetings that were canceled when Trump came in are starting to meet again. Supposedly the first one is today, and I'm trying to confirm that they actually met. So, and the peer review panels are meeting again. And so the grant making process that has been frozen for a couple of months now

should start to unfreeze, at least for some grants, as long as you're not working on some forbidden topic. All right, Jocelyn, thank you so much for catching us up. I'm sure we'll be in touch again. Okay, I'll see you later, Sarah. Jocelyn Kaiser is the editor for Science Insider, our policy news section. You can find all of our coverage at science.org slash scienceinsider. Stay tuned for our conversation about metabolic changes during sleep deprivation with researcher Jennifer Tudor.

When I don't get enough sleep, it's like my brain has shrunk two sizes. I can't focus. I can't remember things easily. And my energy is low all over. Being sleep deprived is basically a body wide experience. But what is actually going on in the body in this state? This week in Science Signaling, Jennifer Tudor wrote a review considering the evidence for thinking about sleep loss as a metabolic disorder. Hi,

Hi, Jennifer. Welcome to the Science Podcast. Thanks so much for having me. I'm excited to be here. Oh, yeah. This is a really fascinating topic. What started you on this path to thinking of sleep loss like this? When I was an undergraduate student at Stony Brook University in New York,

I was really interested in the idea of naps and how maybe what we eat or the sugars that we ingest is going to help with our taking of exams. Fast forward until my postdoc years, I was working in Ted Abel's lab at the University of Pennsylvania. And some of my colleagues, fellow postdocs, were working on this idea of like, what is actually happening during sleep deprivation? And they noticed that

that one of these central dogma questions, DNA being transcribed or copied into RNA, and then that RNA being translated into proteins, something was going wrong there. So they picked up on this and that's when, right when I joined the lab and we decided to take a deeper look into this. And that kind of got me started on this path. So when we feel these things, like we don't have enough sleep,

What exactly are we feeling that's different about our body? What is the effect on the brain, for example? What do we know about...

sleep deprivation, what changes about our brain. Psychologists and neuroscientists have been asking for a long time, what is that thing that makes us feel sleepy and makes us feel kind of woozy and gives us the signal to sleep? And so for a long time, scientists thought it was potentially serotonin, and then they kind of moved on to melatonin. And I'm sure a lot of the listeners out there know about melatonin and taking these melatonin pills to help fall asleep.

Since then, neuroscientists have focused in on adenosine, which is a byproduct. And people might have heard of ATP, which is this idea of the energy metabolite that really our cells run on, right? It is the cash that our cells are spending for energy to do all the work that it's doing.

And so that's kind of what we've been honing in on. And so back in 2016, we published a paper showing that the process to make proteins is decreased with sleep deprivation. And those proteins are really essential to make memories. So that's why our cognitive abilities might be impaired.

But it's not just about the process of making proteins. It's about all sorts of other issues. So one thing I will say, and what we're trying to highlight is that during sleep loss, basically neurons are shunting resources specifically related to energy away from maybe processes that are not particularly essential for cell survival and might be considered more gratuitous, such as memory.

memory. Now, we might not think of memory as being a gratuitous thing. But, you know, you want your cells to live. Right. To form a memory another day. Exactly. Yeah, exactly. Essential survival is probably more key than anything else. Our brains are really energy hungry. We kind of think of them as this top energy user. Is that why to me anyway, it feels like my brain goes first when I'm tired? Some people would say the body goes first when they're tired. Oh, really? Yeah.

Yeah. Some people, they will remark how their muscles feel fatigued if they're sleep deprived and things. But yes, you're right. The brain uses anywhere from 20 to 25% of our blood at any given time, as well as our oxygen, as well as energy.

energy. It's incredibly metabolically costly to run the brain. But one of the things that our paper is also highlighting is that it is a peripheral system as well. As a neuroscientist, I happen to think that the brain runs everything and it is the most important organ in all the body. And so the brain is what's truly regulating sleep. That

being said, I think one of the things that is surprising that you will read in our paper is that there's a lot of peripheral metabolic things that are happening and changing with sleep deprivation. So it's not just in the brain, but it's also in the body. Do we need to understand what sleep is for, why we sleep in order to understand why

why it's bad for us to miss sleep. I was kind of running into this when I was like, okay, well, these are bad things. These don't sound good, but is this why we sleep or is just a consequence of the lack of sleep? There's some excellent work that's been done for 50 to 70 years, actually probably closer to 100 years now, trying to understand the nature of sleep. That being said, it is very clear that

There are many reasons why we sleep. One of the reasons is because when we are awake, there's increased energy expenditure just by moving around and doing whatever we do on an everyday basis. When we sleep, we don't do that. We also know that with wakefulness, we are creating all sorts of metabolic waste.

And then when we sleep, we're able to clear some of that cellular metabolite waste that we have generated throughout the day. There is a robust conversation in the field, really trying to understand, well, is sleep just a way to reset the body and the brain for what we do in the day? Or is there something actively happening during sleep to allow us to function? Regardless of what it is, we clearly need sleep. And every time we miss it, something is amiss during our day.

We talked a little bit about the brain, like you're not going to be building proteins. Maybe you're not going to be making connections and making these long-term memories if you miss out on sleep. What about the rest of the body? What are some of the things that you see with sleep deprivation that say metabolic issues? This is bad.

Sure. So one thing that is clear is that with sleep deprivation, there is less efficient making of that ATP that we need to run ourselves. That is something that's very clear. And there's this basically shunting away from ATP synthase. That's the protein complex that makes ATP.

ATP and instead the cells are generating heat instead. So all that energy is lost to heat. So that's a real issue in terms of ATP efficiency. Another problem is with glucose metabolism. We basically have decreased intracellular glucose levels, and that has a lot to do with insulin growth factor expression and issues there.

Probably the other big thing is actually the connection and the conversation between neurons and glial cells. So glial cells in the brain are their supporting cells. And a lot of neuroscientists, we spend a lot of time thinking about neurons. I know I focus a lot of time on neurons, but there's actually an issue in terms of these supporting glial cells.

And their metabolism is coupled with the neuron's metabolism. And so when that's dysregulated, that becomes an issue in terms of how the cell processes glucose. And essentially with sleep deprivation, there is an increase in these reactive oxygen species and peroxidized lipids. And that also has long-term downstream effects in terms of ATP generation efficiency. So-

It sounds to me like there's a lot going on body-wide. A lot of it is like less efficient doing of your job, whatever your job is with all these different biochemical processes, but maybe napping would help. But would eating more help? Could you eat your way out of sleep deficit if you just had more calories to go around?

The mouse studies and the human studies actually differ as to whether eating your way out of sleep deprivation actually can work. There is this negative energy imbalance that's caused by sleep deprivation. And so what we're seeing in the mice is that they will increase food intake if they're sleep deprived. Now, it could be because they're bored and they're just staying awake and it's like you eat. And to be perfectly honest, there's many of us when we stay awake, we're sitting there just in

inhaling food. Time for the fifth meal. Yep. Exactly. Like we're hobbits or something like that. But even though the mice increase their food intake, we do see a decrease in body mass. So clearly there's something happening there. However, in human studies, there's an increase in food intake and then there's an increase in body mass.

And so the way we've been thinking about this is that there's probably an issue in terms of what we choose to eat when we are doing late night snacking that is leading to that weight increase. So one of the big areas of research right now in terms of metabolism is

sleep and nutrition is the idea of time-restricted feeding and how eating at a particular time, whether it matches with our circadian period or not, could actually have an effect on our metabolism. I would be remiss if I don't point out that there is

a lot of integration between our body clocks and our circadian 24-hour cycle, as well as sleep. So we can't study sleep absent of the circadian system. So we talked a little bit about like how it affects the weight, but does it

kind of reverse some of these things that you're worried about in the brain, in the body when it comes to these metabolic processes to just have more calories on board during times when you don't have a lot of sleep? I think the research is still very young in this area in terms of like what happens if you force feed or feed better at certain time periods in the presence of sleep deprivation. I

I personally don't know of a lot of studies that are really going into that field yet, but it would be fascinating. And it's certainly kind of the next frontier of what can we do when we are sleep deprived?

And eating more doesn't seem to completely make up for the deficit of sleep deprivation. Yeah. So that is kind of my next question. You know, as we understand these mechanisms that are a consequence of sleep deprivation, can we remedy some of that or is napping the only answer?

I hear that the best window of napping is 20 to 30 minutes from my colleagues who really study that area. But I think more important is we have, and I am just as guilty as almost anyone, that when I get busy, the first thing that goes is my sleep.

I will prioritize meeting up with people, seeing students, working on a review paper before I get my sleep. And what we are trying to highlight is truly how profound those changes are in the cells of our body and brain to the point that perhaps we shouldn't dismiss our sleep so easily. That being said, I have a lot of friends who are having lots of babies right now. So I do want to put out

a note there for all of the mothers and fathers who are very, very sleep deprived that there is a rebound effect that happens. So even though mommy brain and daddy brain is real, we do see that there is a rebound effect. One of my mentors and teachers, David Dengis, used to say that you

You can't make up for lost sleep. The whole idea of making it up, it's not a thing because you lose it and you kind of lose it. In the same way you lose time, you're not going to make up the time. If we are more cognizantly aware of how much sleep we are losing, perhaps we can not create the ideal conditions for those deficits, but rather maybe create ideal conditions to protect ourselves.

against possible deficits that can come down the line. One thing that comes up in your review is this idea that some of what we're seeing in the brain under sleep deprivation does look a little bit like neurodegeneration. Is there some kind of parallel there or is this just kind of like dirty brain? Dirty brain.

So I want to be very careful with what I say next. A few years ago, we published a paper and we showed that actually with sleep deprivation, the metabolic environment looks almost the same as a non-sleep deprived aged organism. That sleep deprivation and aging almost looks parallel in terms of those metabolites.

A lot of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease are also associated with sleep issues and difficulties with maintaining and establishing sleep. And actually one of the strongest connections between a neurodegenerative disorder and sleep problems is with Parkinson's disease. And so they're clearly core morbid with each other in terms of sleep.

and neurodegenerative disorders. I don't want to say if you sleep perfectly well that you are inoculating yourself against these disorders. That's not what's happening. But actually, I was surprised as my students and I were doing this pretty in-depth literature review, how intertwined neurodegeneration and sleep potentially could be or sleep loss could be. And so it's important that we pay more attention to it. I think

That's part of the reason why we have such a provocative title for our paper. We really want to draw attention to this idea. I think some people think sleep is a luxury, but it really is essential for us to have probably the most ideal working conditions for our bodies. That's great. All right. Thank you so much, Jennifer. Thanks, Sarah. I really appreciate it. Jennifer Tudor is an associate professor of biology and Warren Chair of STEM Disciplines at St. Joseph's University in Philadelphia.

You can find a link to the science signaling review we discussed at science.org slash podcast.

And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at sciencepodcast at aaaas.org. To find us on podcasting apps, search for Science Magazine or listen on our website, science.org slash podcast. This show was edited by me, Sarah Crespi, and Kevin McLean. We had production help from Podigy. Our music is by Jeffrey Cook and Wenkui Wen. On behalf of Science and its publisher, AAAS, thanks for joining us.

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