Short Wave - Embracing Death: Why We Age

Episode Date: October 29, 2024

Humans have seen a significant increase in life expectancy over the past 200 years — but not in overall lifespan. Nobody on record has lived past 122 years. So, for this early Halloween episode, host Regina G. Barber asks: Why do we age and why do we die? Microbiologist Venki Ramakrishnan explains some of the mechanisms inside of our bodies that contribute to our decay — and tells us if it's possible to intervene in the process.Curious about other biology news? Email us at [e-mail] and we might cover your topic on a future episode! See 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

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News Survival Kit from NPR podcasts. All right. Thanks for listening. Here's Shortwave. You're listening to Shortwave from NPR. Hey, Short Wavers. Regina Barbara here with my favorite co-host Emily Kwan. Hey, Emily. Gina, I'm your only

co-host. Yeah. Do you have plans or something? No, this is like it's why it's easy to pick, you know? Fair. Okay, so let's start. I have a question or maybe a riddle for you. Uh-huh. What do we, and all animals, plants, living things have in common. No matter how desperate, we try to escape it.

Farts. Like poop. Like we all make waste. I like that. No. Oh. What I'm going for, I'm going to tell you, we all have to die. Oh, we're going there. Yeah. It's Halloween.

Happy Halloween. Happy Halloween. Time to talk about death. So to me, death is like one of the big scientific mysteries. We can try to like do anything. of the sun to like deny it, to delay it, to stop it. But what does dying even really mean? Well, it's a peculiar situation because we're a collection of cells.

And when we're alive, millions of our cells are dying. And a lot of that cell death is actually required. So this is Vanki Ramakrishnan. He's a molecular biologist who wrote a book this year called Why We Die. When we die, most of our cells are still alive. And the fact is that you can donate entire organs to transplant recipients. And so what does it mean to say you die? Isn't death when you no longer have brain activity?

Yeah, legally for now, that's the, you know, criteria. But for a while, we considered someone dead if their heart stopped beating. Before we learned, we can reverse that through CPR. And now there's even hints that even loss of brain function is reversible. Whoa. Yeah. Vanky says that basically we should think about death as like an irreversible loss of consciousness. Case more or less closed, like details aside.

Permanent loss of consciousness, that's death to a scientist. Yeah, right. So the more interesting question, though, to Vanky is why humans have to die? Like, if all is going well, like you're healthy, you're eating and sleeping well, you look out genetically. You're the most careful person in the world. Like, why do we have to die at all? Okay, life expectancy has increased on average, but it's true no one is living past 100-something. Like the oldest living person went around 120. Right, yeah, we're not going to live forever. No.

And for a lot of diseases like cancer, cardiovascular disease, high blood pressure, diabetes, dementia, the biggest risk factor is aging. Which in its simplest terms is this buildup of damage to our molecules, cells over time that lead to our death. So as you age, you're becoming more damaged. Yeah. Yeah, I mean, we all kind of know it internally. And we're like at a point now, we're in order for people to like live longer. We really have to tackle like why we age. Yeah.

Like can we take a note from other animals and learn to age better? Be like the tiny, tiny hydras in the water or like naked mole rats or like the Galapagos turtles. All these animals just like age way slower than us and mostly die from like, Predators are starvation, not cancer. So there's this vast variation, and yet we're all made of the same material, presumably subject to this similar wear and tear. So it is a matter of scientific curiosity about what causes aging, what determines the rate of aging, and whether that rate can be slowed down.

So today on the show, the inevitability of death. We dig into the biological research that tells us more. about how aging happens on a cellular level and whether or not it's possible to postpone it. You're listening to Shortwave, the science podcast from NPR. Okay, Gina. So before we get to aging, can we start with how our cells work when we're young and healthy? Okay. And everything is working. Yeah, so remember at baseline, our cells are always dying, like even in a fetus.

And to be clear, they should do that. Why is that? Well, when cells undergo stress or have, like, DNA damage of some kind, the body. body will often send cells to death because they're a cancer risk. And we have so many cells that it's better like to lose them. That makes sense. Yeah. So either the cells die or they get sent into a state called senescence, which is where they stop dividing.

They secrete this inflammatory compound to signal to the body like, hey, we need some attention over here. There's a virus or something causing damage and we need repair. It's just like inside out. Except on a cellular level. Right, right, right. Yeah. That seems good. Yeah.

But. What happens as we? get older is more cells start to die and many more cells start to die than we can handle properly. We start producing more senescent cells because, you know, cells accumulate defects faster because a lot of the repair mechanisms are breaking down. And then the machinery to deal with the senescent cells is also not working as well. So we get a build-up of senescent cells, which just results in a buildup of inflammation. And this inflammation can actually cause more cells to go into distress and spread senescence.

And so it's a vicious cycle. So it's like a compounding traffic jam in our bodies as we get older. Yeah, exactly. But then why are our cells accumulating defects in the first place? Why can't they just, like, be perfect? Yeah, that's a really good question. So DNA gets replicated like all the time, since our cells are dividing all the time, right? So one big way DNA gets altered is through that replication process.

So the way that cells replicate their DNA depends on a particular machinery. Think of them as the DNA copying machines or enzymes that copy the DNA. So where you have one strand of DNA, you'll now have two. Well, that copying machinery is unable to copy the very ends of DNA. And so each round can result in shorter DNA. Our DNA strands can get shorter? Yeah, it's like a game of like genetic telephone. Like you keep on losing stuff.

And something Vanky told me that helped me like understand this was to imagine like this DNA copying machine as like an engine sitting on a railway track. And it can reproduce all of the track that lies ahead of it. And as it chugs along the track, it can reproduce the track. of it. But what it can't do is reproduce the track that it was sitting on at the beginning. Right, right. That makes sense. So it's a little bit like that. Huh. Because it's like somehow using that or like there's some interaction with the bit of material it can't replicate. That's right. Okay. So because DNA keeps replicating,

part of that process means it does get shorter and may miss more and more genetic information. Yeah, yeah. So then the vicious cycle, like, like, you know, of senescence and inflammation, it starts again. But our bodies are amazing and have built in a little protection against this, a cap on the ends of our DNA to protect that important genetic information. And that built in protection, it's called telomeres. Oh, I know telomeres. What do they look like exactly?

So, yeah, so on a DNA helix, telomeres are the little ends of the strands, like the protective plastic caps on the end of like shoelaces. Uh-huh. And there are two on top and two on the bottom. Yeah, all right. And telomeres are made up of what are called DNA repeats. They don't code for a particular gene, but they're there to maintain a particular structure. Which allows DNA to go through that replication process and shorten the telomeres with all the repeats instead of shortening the part of the DNA that holds the important genetic information that the DNA needs.

And that way, as the DNA replicates, your body isn't losing some of that critical information. and it's maybe slowing down the damage? Yeah, and the telomere's structure is also important for like another reason. As long as that special structure is maintained, the cell doesn't see the end of the chromosome as a broken piece of DNA. But when cells keep dividing and the telomeres become shorter, at some point they become too short for that structure to be maintained. Suddenly the cell sees the ends of the DNA,

DNA as a break, it can't distinguish between a break in the DNA or the end of this unraveled telomere. And that triggers the DNA damage response. And when that DNA damage response is triggered, the cells go into senescence. Oh, okay. So back to senescence. Yes, senescence. When your cells can't divide anymore and die. Okay. So basically, the body's response to handle DNA damage is telomeres. And while it helps us, it does eventually fail and accelerate aging. Yeah. And there's like a lot of other possible contributing factors to aging too, like methylation. Partly, this is added on as a result of our environmental history. For example, in stress, you would increase methylation of your DNA. What's methylation? It's when your body

uses methyl groups, which is just CH3, a carbon with rehydrogens, to silence parts of your gene. Now, you might ask, why does the cell need to do that? Well, as cells differentiate, they don't need all the genes. For example, your skin cell doesn't need the same genes that your eyes do or your neurons do or your red blood cells certainly don't need, you know, cells that are involved in touch or heat sensitivity. So methylation is trying to like make your body more efficient. Yeah, but methylation is a with dysfunction later in life, though, because the process may be turned off too many genes that you actually might need later. And actually, these methylation patterns we pick up through our lives tell us way more about, like, how much our bodies have internally aged than our chronological age, which is just like how many years we've been alive. Like, I'm, you know, almost a decade older than you. But, you know, we might be, like, internally the same. You know, our methylation patterns might be similar. What I'm also realizing is that, All these mechanisms that our body have in place to protect us and make them grow and thrive eventually leads to our demise.

It's kind of tragic. Yeah, it's a complicated puzzle. And there are researchers out there that are trying to, like, see if knowing about the way our body ages can maybe give us more information about how we can slow aging. Like, if you can reverse methylation and then maybe reverse aging. That's an interesting hypothesis. Is that possible? Yeah. You can reverse.

methylation patterns using particular tricks. You can do it in animals, but not so easily in humans. Yeah, we're not so sure about, like, how to do that. We're not even sure, like, methylation actually causes aging, just that it correlates with it. Okay. Are there other things people are looking into to slow aging? I did ask Ban Ki that. We talked about senescent cells and how they accumulate and cause inflammation. So there are a number of trials going on now. for drugs that will specifically target senescent cells. And if you can kill off senescent cells as they accumulate,

in animals that has really improved many of their symptoms of aging. Okay, so there's the drug route, maybe. Yeah, and there's, of course, the, like, the scarier directions this could be going. Another area is a slightly macabre experiment where an older animal was connected to a younger animal and their blood supplies were connected. Oh, my gosh. That sounds like vampiric. Exactly.

So the young blood apparently had beneficial effects on the older animal, but even more so, the old blood had detrimental effects on the younger animal. Oh, my gosh. And so what this means is that as we age, the components of our blood change. So there's a lot of research going on to ask what has changed and which of those changes are relevant to aging, and then to ask how do they work, and then see if those factors can be used.

And, of course, this has long-term research and it's ongoing, lots of labs working on it, but it hasn't stopped companies from sprouting up, selling young blood from young donors. Yeah, very creepy. In fact, the professors who discovered this at Stanford, they described that when they published their paper, they started getting all these creepy,

phone calls from people, you know, wanting to know how they could use this. That is so creepy. Yeah, right? And it's like on one hand, obviously I want people to like not suffer from disease, not age super fast. That's the goal. Yeah. But like at the same time, it's also scary to me like how badly people seem to want to

evade like death and aging. I mean, it's understandable. It's me too. I think I've come to terms with like there's so many things that I can't control and aging is like death is like number one. So, you know, I just accept this is what my body's designed to do. Okay. Die. Maybe I'll get there soon.

I'm going to get there sooner, maybe. And I don't have a choice. This episode was produced by Jessica Young and edited by a showrunner Rebecca Ramirez. Tyler Jones checked the facts. Quasi Lee was the audio engineer. Beth Donovan is our senior director and Colin Campbell is our senior vice president

of podcasting strategy. I'm Regina Barber. And I'm Emily Kwong. Thanks for listening to Shortwave. from NPR.