'Zombie' Cells Could Explain Aging — And Help Scientists Slow It

It’s no secret that stress isn’t good for you. But just how bad is it? Well, in the last few decades, scientists have linked psychological stress to changes in our DNA that look a lot like what happens on the molecular level as we age. Today on the show, host Regina G. Barber https://www.npr.org/people/1082526815/regina-g-barber talks to freelance science journalist Diana Kwon https://www.nature.com/articles/d41586-025-01886-3 about the latest research on stress and aging, including a new hypothesis for how your brain handles aging — and what science could do about all of it. Interested in more aging science? Let us know at [email protected] mailto:[email protected]. Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ atplus.npr.org/shortwave http://plus.npr.org/shortwave. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:00Speaker 00

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• 0:22Regina Barber?

  Hey, Short Wavers. I love my job, but I'm going to be honest, sometimes it's stressful. And when I'm stressed, I can definitely feel it in my body, which science journalist Diana Kwan says makes sense.

• 0:34Speaker 02

  I've reported a lot of stories in the past about the biological effects of stress.

• 0:39Regina Barber?

  Stress can really take a physical toll, but I don't think I realized just how much of a toll until this episode, when I called her to discuss the link between stress and aging. And she told me, yep, Gina, there's a whole body of research on this very topic.

• 0:56Speaker 02

  It just kind of made a lot of sense that stress sort of affects aging as well because, you know, things like various disorders and diseases, you know, these all affect how quickly we age.

• 1:05Regina Barber?

  She told me about a study researchers did in the early 2000s, looking at stress in 58 biological mothers.

• 1:12Speaker 02

  About a third or a bit more than a third who had a healthy child and 2/3 who had a child with a chronic illness. And they kind of reasoned that this latter group would have higher levels of stress due to having to take care of somebody with an illness.

• 1:28Regina Barber?

  Part of the study included asking those parents about their stress levels, which were higher for the caretakers of kids with an illness. But Diana says this study also did something pretty unique.

• 1:39Speaker 02

  It was one of the first studies to really bring the stress and aging link to like the molecular level.

• 1:45Regina Barber?

  So more researchers started looking for signs of psychological stress in people's DNA.

• 1:51Speaker 02

  You know, not only did this group of people with a chronically ill child report having higher levels of stress, they also had shorter telomeres.

• 2:01Regina Barber?

  Telomeres are the protective caps on the ends of chromosomes. And overall, their shortening is associated with aging. So more stressed parents with shorter telomeres equals biologically older parents. Since then, other studies have found other clues to how stress affects the body on the molecular level. They linked chronic stress to an increase in something called senescent, or zombie cells.

• 2:24Speaker 02

  As our cells age, they stop performing their regular functions and they enter this kind of sleepy zombie-like state.

• 2:33Regina Barber?

  And they stop dividing, like normal cells do. Some researchers are starting to think that these zombie cells are sucking up resources from the rest of our body, which ultimately results in aging. And could ultimately help researchers answer the question.

• 2:48Speaker 02

  What is it about stress that's changing our cells that, you know, makes people become less healthy later in life?

• 2:56Regina Barber?

  Today on the show, a new hypothesis for how the brain handles these aging zombie-like cells may help researchers understand aging on the molecular level. Plus, what science could do about it. I'm Regina Barber, and you're listening to Short Wave, the science podcast from NPR.

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• 4:37Regina Barber?

  Okay, Diana. So these researchers that are like studying aging, they've developed this hypothesis called the brain-body-energy conservation model. As a physicist, I love any energy conservation model, actually. How does this work?

• 4:50Speaker 02

  Yeah, yeah. So this is a really interesting model developed by, you know, a small group of aging researchers. So it's by no means a well-established, widely-accepted model yet. But basically, as our cells get older, you know, they accumulate energetically costly forms of damage. So these are things like becoming zombie-like or senescent, or accumulating DNA damage, or inflammation, you know, all of these things are...

• 5:20Regina Barber?

  Those telomeres shortening.

• 5:22Speaker 02

  Exactly. So all of these things require energy to fix. And so the brain, through, you know, various signaling molecules that are coming through the body, senses that, okay, there's a bunch of cells out there that need energy. And so we're going to take energy away from other processes to fuel this damage control. And so this ultimately results in the outward signs of aging that we're all familiar with, things like growing hair or reduction in muscle mass that are less essential than keeping our cells alive.

• 5:54Regina Barber?

  Yeah, it makes me think of like how older appliances, like fridges, you like use more energy. They're less energy efficient like than the newer ones that are like running well, you know?

• 6:03Speaker 02

  Yeah.

• 6:03Regina Barber?

  So in your piece, you write about an experiment these researchers did, the ones who came up with this model, a couple of years back to look at how these zombie cells use energy. Can you tell me more about that?

• 6:14Speaker 02

  Yeah, so this was back in, I think, 2022, where a bunch of researchers at Columbia took human skin cells and cultured them in a laboratory dish. And they observed them over a short period of time. And they found that the cells that had stopped dividing and entered this zombie-like state... We're using about double the energy that younger cells were. And this kind of flew in the face of what researchers had thought about these zombie cells, because, you know, a lot of people thought, okay, a cell doesn't divide anymore. Cell division requires a lot of energy, you know, these cells must not, must not need a lot of energy. But actually, it turns out that they're burning a lot of energy. And so, you know, the researchers went and kind of looked at the literature and found,

• 6:59Speaker 02

  oh, wait, there's like all of these other damage processes that are happening, and these are all costly, you know, we should put this into a model. And, you know, the brain-body energy conservation model is what they came up with.

• 7:10Regina Barber?

  And this is a pretty new hypothesis, right? Like, the entire aging research community isn't completely convinced yet, right?

• 7:19Speaker 02

  Yeah, it's absolutely a new hypothesis. They only came up with it, you know, in the last couple of years. And the researchers I spoke to who hadn't developed this hypothesis, a lot of people thought it was really intriguing. And I think what a lot of people like about it is that it kind of brings the brain and body together in aging, and that's something that hasn't really been done before, this kind of unified hypothesis of aging, one can kind of think of it in that way. But, you know, in a lot of ways, a lot of pieces of this puzzle are untested, even though there are some really compelling hints or pieces of evidence that, you know, this might actually be happening.

• 7:58Regina Barber?

  Right, yeah. One of these things that has come up in these studies is this molecule called GDF15. Why is this important in this research?

• 8:07Speaker 02

  Yeah, so GDF15, or Growth Differentiation Factor 15, which is a bit of a mouthful. So I think this was one of the most fascinating pieces of the brain-body aging model puzzle. So basically, GDF15 is a cellular messenger, and...

• 8:28Speaker 02

  Researchers think it might play a really central role in mediating the link between the body and brain and aging. And this molecule has also come up in aging research, sort of not related to the brain either. So it's been linked to a bunch of different aging-related processes. Once again, cellular senescence or a zombie-like state. So you know, the, this molecule is found to be linked to that process. Also a dysfunction in mitochondria or the cellular powerhouses. This is also something that happens as we age. G D F fifteen is also linked to aging-related diseases like Alzheimer's and a bunch of chronic physical and mental illnesses too. And so, one thing that's really interesting about this molecule is that it's secreted

• 9:11Speaker 02

  by many, if not all of our organs, but the receptor for this molecule is only found in one place in the body, and that's in the brain. And so, you know, all of these things together, yeah, have made researchers think, okay, maybe G D F fifteen is responsible for sending the brain's signals about cellular stress. So this is kind of a working hypothesis at the moment, but a really fascinating molecule that might play a really important role or be a really important piece of this whole puzzle.

• 9:42Regina Barber?

  There are so many unknowns still, but scientists are already trying to create medicines, like to slow down aging. So with this new hypothesis, how are scientists going to maybe think differently about clinical trials?

• 9:54Speaker 02

  Yeah, I think both with this new hypothesis and the kind of growing body of research that shows that stress plays a really important role in these aging-related processes. What a lot of the stress researchers or the stress and aging researchers that I spoke to said is that, you know, this field of aging, which traditionally hasn't really thought about the effects of stress, should really think about how much stress the people who are taking these drugs or, you know, will be taking these drugs in the future are exposed to because that might have a huge impact on how well these interventions work.

• 10:27Regina Barber?

  When you were doing this story, at the very end, when you've done all this reporting, did you come away thinking differently about aging, about stress?

• 10:36Speaker 02

  I guess yes and no. No in that, you know, I wasn't necessarily surprised that stress, which affects so many parts of our body, affects aging as well. But I guess yes, in that for such a long time, it was kind of this like woo woo connection. Oh, you know, stress causes aging, but you know, how without a mechanism? So I thought it was really cool that this research is seems to be entering a kind of new era where, you know, hopefully it'll start to make a big difference in people's lives.

• 11:05Regina Barber?

  Yeah, I mean, this actually does make me feel like more hopeful as well about about stress and aging.

• 11:10Speaker 02

  Yeah, absolutely. And that makes me think of, you know, there's actually been some experiments where scientists have found that some of these stress-related aging changes in our cells are reversible. So there were researchers who did a study in monkeys where they found that monkeys that were stressed out had these changes in their immune cells that were linked to accelerated aging. But they found that when they switched up their conditions and put them in less stressful situations, you know, all of a sudden the cells bore less or reduced signs of accelerated aging. So I think that's a really positive thing because I think the this kind of stress may be linked to aging or cause aging at some level. It can be a really negative message and it can stress people out to think that

• 11:53Speaker 02

  stress is going to age you because, you know, stress is one of these things.

• 11:56Regina Barber?

  You're stressed because you're stressed about stress.

• 11:58Speaker 02

  Exactly.

• 11:58Regina Barber?

  Yeah.

• 11:59Speaker 02

  But no, these changes are not irreversible. These are things that, you know, we can affect in our daily lives to some extent. It's it's kind of more hopeful in my view. It's a hopeful view of the future where we will have a toolbox of things that may help us stay healthy for for longer.

• 12:16Regina Barber?

  Yeah, and less stressed.

• 12:17Speaker 02

  Yeah.

• 12:20Regina Barber?

  Diana, thank you so much for talking to me today about aging. It makes me think about aging, you know, more because I always think about it.

• 12:28Speaker 02

  Don't we all? Thanks so much for having me.

• 12:32Regina Barber?

  Shortwafers, thank you for listening. If you want to help us out, share this episode with a friend. We want to grow as we age and reach even more science curious people. And that's one of the best ways to do it, by word of mouth, from you to your friends. And why not follow us on the NPR app or whatever other podcast app you use. This episode was produced by Burley McCoy, edited by showrunner Rebecca Ramirez, and fact checked by Tyler Jones. The audio engineer was Jimmy Keely. Beth Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barber. Thank you for listening to Short Wave from NPR.

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