Regina Barber (2:47)

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

Diana Kwan (2:54)

About a third or a bit more than a third who had a healthy child and two thirds 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.

Regina Barber (3:10)

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.

Diana Kwan (3:21)

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

Regina Barber (3:27)

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

Diana Kwan (3:32)

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.

Regina Barber (3:43)

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 and to an increase in something called senescent or zombie cells.

Diana Kwan (4:06)

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

Regina Barber (4:16)

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 what?

Diana Kwan (4:30)

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

Regina Barber (4:38)

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 Shortwave, the science podcast from N.

Unexplainable Host (5:03)

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Regina Barber (8:54)

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? Yeah, yeah.

Diana Kwan (9:08)

So this is a really interesting model developed by 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, 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 those telomere shortening. 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 graying hair or reduction in muscle mass that are less essential than keeping ourselves alive. Yeah.

Regina Barber (10:11)

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.

Diana Kwan (10:20)

Yeah.

Regina Barber (10:20)

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

Diana Kwan (10:31)

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 were 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 a lot of people thought, okay, a cell doesn't divide anymore. Cell division requires a lot of energy. These cells must not need a lot of energy. But actually, it turns out that they're burning a lot of energy. And so the researchers went and kind of looked at the literature and found, oh, wait, there's all of these other damage processes that are happening, and these are all costly. We should put this into a model. And the brain body energy conservation model is what they came up with.

Regina Barber (11:27)

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

Diana Kwan (11:35)

Right? Yeah, it's absolutely a new hypothesis. They only came up with it 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 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 this might actually be happening.

Regina Barber (12:15)

Right.

Diana Kwan (12:15)

Yeah.

Regina Barber (12:16)

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

Diana Kwan (12:24)

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 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, not related to the brain either. So it's been linked to a bunch different agent related processes. Once again, cellular senescence or a zombie like state. So this molecule is found to be linked to that process, also a dysfunction in mitochondria or these cellular powerhouses. This is also something that happens as we age. GDF15 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 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 all of these things together. Yeah. Have made researchers think, okay, maybe GDF15 is responsible for sending the brain 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.

Regina Barber (13:59)

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

Diana Kwan (14:11)

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 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 will be taking these drugs in the future are exposed to, because that might have a huge impact on how well these interventions work.

Regina Barber (14:44)

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?

Diana Kwan (14:53)

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 seems to be entering a kind of new era where hopefully it'll start to make a big difference in people's lives. Yeah.

Regina Barber (15:22)

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

Diana Kwan (15:27)

Yeah, absolutely. And that makes me think of. 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, 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 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 stress is going to age you because stress is one. Cause you're like you're stressed about stress. Exactly. But no, these changes are not irreversible. These are things that we can affect in our daily lives to some extent. 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 longer.

Unexplainable Host (16:33)

Yeah.

Regina Barber (16:33)

And less stressed.

Diana Kwan (16:34)

Yeah.

Regina Barber (16:37)

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.

Diana Kwan (16:44)

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

Regina Barber (16:48)

Short wavers. 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 Burleigh McCoy, edited by a showrunner, Rebecca Ramirez, and fact checked by Tyler Jones. The audio engineer was Jimmy Keeley, 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 N.