Tickling in review, spores in the stratosphere, and longevity research
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This is the Science Podcast for May 29, 2025. I'm Megan Cantwell filling in for host Sarah Crespi. First up, online news editor Michael Gresko joins Sarah to go over a handful of stories, from chemical hints of life on an exoplanet to finding fungal spores all the way up in the stratosphere. Next on the show, I talk with Constantina Kilteni about why it's so tricky to understand the science of tickling.

Finally, as part of our series of books on the science of death and dying, host Angela Saini interviews author Venki Ramakrishnan about his book, Why We Die: The Science of New Aging and the Quest for Immortality.

Now we have Michael Greshko. He's an online editor for our news site, and he's going to talk about three space-related stories with us this week. Hi, Michael. Welcome to the Science Podcast for the very first time. Thank you so much for having me. It is honestly such a treat to be here. We're going to talk about space, but we're going to start close to Earth and then move out.

So stratosphere is, I guess you could say the edge of space. It's very far up. This is where planes fly. This is where the ozone layer is. And also fungal spores, right, Michael? That is right. Yeah. So stratosphere is about 10 kilometers up. Not quite the internationally accepted boundary of space. But if you were just up there exposed, it would not be a fun time. It's super cold up there. Air pressure is extremely low. And a lot of the stratosphere is

above the ozone layer. So you also have ultraviolet radiation to contend with, which is why researchers are so interested in the fact that fungal spores can... Survive? Get up there? Exactly. One of the big questions...

that the researchers have been interested in is the extent to which fungal spores sort of ride the stratosphere, kind of like an intercontinental superhighway. This might, for example, be one of the many factors that influences how fungal pathogens that affect plants or even people move from place to place. But of course, sampling the stratosphere, it's not quite like sticking a butterfly net out the window of a plane.

That's really the cool thing here is the low, low price of the process for sampling. What do the researchers do differently than they've done in the past to kind of grab up these spores? There's this really interesting research team out of Switzerland that has come up with like a really cost-effective MacGyver solution for this. Basically piggybacking off of weather balloons, coming up with this very small payload, less than two kilograms, that contains

an altimeter, some basic electronics, a camera, and a little device that can open and shut two ports. So what happens is as the weather balloon gets up to a certain altitude, these ports open and there are four sterilized matchsticks and they're covered in petroleum jelly. The idea being that as air from the stratosphere is passing through the device, if there's any fungal spores hitching a ride on that air,

Those petroleum jelly coated matchsticks are going to catch at least some of them. That does sound very MacGyver. So how do you get them back? Eventually, these weather balloons that these packages are attached to, they pop at about an altitude of 35 kilometers. And these packages then parachute back down. Of course, it's not as if they can control exactly where they go down. So the research team has been very careful not to launch them.

when wind conditions would either mean their packages end up way high up in the Alps or like plopped into Lake Geneva. Those are the hazards on this big course. Those are the big ones, yeah. But they have picked these things up off of rooftops and fished them out of trees. Now it's time to analyze those matchsticks, right? What do they find adhered to the Vaseline on there? In the samples that they've taken so far, they have sequenced the

the DNA of actually 235 different genera of fungus that they've been able to... That's a lot. Yeah. And not only that, they've been able to culture in the lab spores from 15 different species. So they're viable. They're viable after they get back down. At least some of them are. Now, it's not entirely surprising that not all of them were able to be cultured because a lot of fungi have...

obligate plant hosts and you can't just culture it in the lab like you need the plant. But the fact that at least some of them did survive and are viable is not only confirmation of the fact that spores can survive these really brutal conditions up in the stratosphere, but is also great validation for this MacGyver way of being able to sample the fungal diversity that's hitching a ride

on the air up in the stratosphere. And this paves the way potentially to doing these kinds of balloon launches in a dedicated, systematic way. Once you do something like that, then you could make a more systematic exploration of like what spores are doing all the way up above our heads. The stratus biome. That's right. The stratobiome. I love that. We're going to move a little further out, just 120 light years away. Yeah, just a hop, skip and a jump.

to an exoplanet called K2-18b. Back in April, we heard of potential signs of life there, but the pushback was almost immediate. Let's get into some background here. Why is it so hard to see or know anything about exoplanets? I mean, for one, you are looking for a planet

tens to hundreds of light years from Earth. So like right out of the gate, not easy. It's harder still to have the right kinds of star systems where you can start to make actual measurements of a planet's atmosphere. And in this case,

What you do is you wait for the planet to transit in front of its home star. And when that happens, starlight filters through the planet's atmosphere. Now, depending on the molecules that are bouncing around in that atmosphere, certain wavelengths of light are going to be absorbed. And so we can infer based on that the presence or absence of different compounds.

kinds of molecules and get a sense of their concentration. Yeah, just 120 light years away, we're doing, what is it called? Spectrometry. That's right. We're looking at the way light is influenced by the presence of molecules. It's so far away and it's a delicate, delicate thing to do. These kinds of measurements have been done at a planet called K2-18b. It's a little more than two and a half times

The diameter of Earth, it's like eight and a half to nine times the mass of Earth. This is a kind of planet that we call a sub-Neptune. It's bigger than Earth. It's smaller than Neptune. I love these names. Now, a few years ago, there were some measurements of this planet's atmosphere that some researchers at the University of Cambridge argued indicated that the atmosphere had

a lot of methane, a lot of carbon dioxide, not a lot of ammonia, which is kind of weird relative to our baseline here, which would be something like Uranus or Neptune. Basically, their model was, okay, we can explain this kind of atmosphere if this is actually like a water world. Now, the second that you model a planet that

that has a full ocean of liquid water, you immediately start to ask questions about, okay, well, what is the habitability of this world? And the same group of researchers announced last year or maybe two years ago that they, using NASA's James Webb Space Telescope, had found potential signs

of another gas in this planet's atmosphere, a gas called dimethyl sulfide. Now, you don't necessarily know the name dimethyl sulfide, but you know the smell. When you go to the beach and you smell like the bracing sea air, that's dimethyl sulfide. On Earth, it is prodigiously produced by marine algae. And so it was argued that the detection of dimethyl sulfide in the atmosphere of K2-18b may be represented a sign for life.

And last month, the same research team doubled down. They used a different instrument on JWST and claimed that they had once again detected dimethyl sulfide. This is a lot of steps. So here we are reading these signatures from the atmosphere, from this glancing light passing through it and saying, OK, we have a water world. And then on top of that, we have a biosignature. We have

a chemical structure that we expect to be associated with active life on a planet, an ocean world. I can see why some people had some questions. This is a lot, but it is a very cool idea. So a few weeks later, the pushback came in three different forms. Let's first start with a chemical in the atmosphere that might be indicative of life. So dimethyl sulfide, first and foremost, doesn't

off to be made by life. You can make dimethyl sulfide through non-living chemical processes. And the other piece of this too is...

What you're essentially doing when you're doing this full analysis of starlight filtering through the alien atmosphere is you are trying to fit a curve. You're trying to fit a curve in the spectra and you're trying to use varying combinations of the spectra of different molecules. Any number of other gases could be included that could give you just as good of a fit given the error bars on the measurement, which brings us to the other point,

which is that this is a really hard measurement to do. And JWST is like an incredible piece of kit, but like we are pushing it to the limits already with something like this. And so another line of argument here is that these data just simply aren't strong enough. They're not high resolution enough

And the third pushback, which I thought was kind of the worst one, was maybe this isn't a water world. Maybe this is a lava world. This gets us back to kind of the fundamental here, which is that we have to explain the spectra through kind of a model of how the planet works geochemically. But there are groups out there that fundamentally disagree with this geochemical model for K218b.

Some have modeled it as maybe it's a lava world, which you and I can imagine would be decidedly less friendly to marine algae. And then there are some, you know, who say, OK, well, maybe it's actually just it's like an ice giant, like a Uranus or a Neptune, kind of like others we've seen. So the first step here, which is like figuring out what kind of planet this is, hasn't really been solidified. This is a lot of steps away from what we know. It sounds like something we're going to have to stay tuned for.

Our last story is on very old star catalogs. A new analysis suggests a star catalog from China may be 2,400 years old.

This is an ongoing battle for supremacy, for oldest catalog, a battle of the stars charts. That's right. Why, Michael, has it been so difficult to tell how old the star catalog is? This particular star catalog known as the Star Manual of Shishen has been with us for well more than 2000 years. Where things get tricky, though, is the fact that these records have been

down through the ages and compiled and recompiled and combined with other works in the same astronomical tradition. Many historians had considered the Star Manual of Shishen as a work created roughly 2100 years ago. Now, this new study by two Chinese astronomers uses contrasting

computational techniques normally used in the context of image processing to try to figure out basically when these measurements would have been made based on how inaccurate they are relative to the present.

inaccurate in that like they didn't know or because the stars look different in the sky now than they did then? Because the stars look different in the sky now. If you look at Earth, if you were to just imagine us sort of zooming away from Earth and just looking at it rotating on its axis, much like a top wobbles, Earth's axis of rotation processes on a 26,000 year cycle. And so

if we got in a time machine and went back 2000 years ago and tried to carefully measure the coordinates of stars on the night sky, and then we jump back to the present, did the same thing, our coordinates would be slightly off because Earth's axis of rotation has processed by some amount. So by computationally looking at the star manual of Shishan and the coordinates in those, what they find is that they get the best fit

If about half of them are from, you know, roughly the first century B.C., so maybe part of that whole effort 2,100 years ago to compile all these records together. But half of them seem like they were put down roughly in the fourth century B.C., around the time Shishan is thought to have lived.

So like 300 years earlier. Correct. Oh, well, it would make sense that if when he was alive, he was doing this. But this is part of the challenge, too, which is like it's also reasonable that he was this astronomer of legend and that people a couple hundred years after he lived and died who ascribed to kind of his tradition of... Right, used the methods. Used the methods and compiled these things under his name. This is a really interesting way of doing this.

Looking at the sky, looking at the charts and saying, this is how much time has passed. But this is not something everyone is buying. Again, there is debate in the community. Very much so. Why are people thinking this method may not be the best way to understand the age of the catalog? The researchers who did this analysis basically took the coordinates for what they were and ran their analysis off of that. And that raises the hackles of some historians who say you very much cannot do that.

in part because the possibility that the instruments that were used when these measurements were taken were misaligned by some amount. This raises a kind of a bigger question. What instruments would you use to do this? As far as historians who've looked at this can tell, the instruments that would have been used to do this included something called an armillary sphere. The best evidence for that kind of instrument existing in China goes back only about 2100 years ago.

So there maybe there wasn't one yet. So why would we expect they were using it to make coordinates? Hypothetically, while

the formal instrument known as the armillary sphere didn't exist back in the time of Shishen, some of these general concepts and understandings did. This is still very much debated. Why is it so hotly debated? Like, why does it matter if we shift which star catalog is oldest? Like, what are the other contenders here? The previous record holder in this category is a record produced by the Greek astronomer Hipparchus, you know, some 2,000 years ago. And so part

Part of the context here is that there is this political and cultural component to right was a particular place in time, the origin of something or the oldest instance of something. People like to say that. People like to say that that carries weight and is also just on its own terms. It's part of a broader effort to try to more comprehensively tell the

the global story of the history of science. And so figuring out what preceded what and what was happening in parallel to something else gives us a fuller understanding of our predecessors grappling to understand the natural world. It is very cool to look so far back and see how long it's been happening. Oh, absolutely. One of the things that so interests me about

the history of science and just historical stories in general is that it really puts us like in communion with our equivalence in the distant past and just makes our full story that much more human. All right, Michael, that's all we have today. Thank you so much for talking with me. Thank you so much for having me. It's been great. Michael Gresko is an online news editor for Science. You can find links to the stories we discussed at science.org slash podcast.

Stay tuned for my interview with Konstantina Kilteny on better ways to study tickling in the lab.

I personally hate being tickled. It makes me feel out of control. And when I'm laughing, it's definitely not a sign that I'm having fun. And I was surprised to learn that we don't even know why exactly we laugh, even if we don't enjoy being tickled. Konstantina Kilteny wrote a review in Science Advances about the challenges researchers have to overcome in order to unravel the science of tickling. Thank you so much for joining me, Konstantina. Thank you very much for inviting me. Well, first, I think we have to ask,

whether you laugh when you're tickled. I laugh a lot when I'm being tickled and I really hate it personally. It's not fun. It's not fun at all. I don't like it. It's not just a human phenomenon, right? No, also great apes respond to ticklish stimuli.

Studies in rodents, ticking studies, where they record sounds, these researchers argue that these responses are the equivalent of human laughter. They are ultrasonic calls around 50 kilohertz. When we're conducting studies when it comes to tickling rodents,

How do we do that? Is there an agreed upon type of touch? I've seen the videos of them tickling the mice and it looks pretty aggressive, but I know when you're doing it on humans, it could look different. You will find a lot of variety in the studies that are about human ticking. Most of the studies from the 90s and early 2000s

People are coming in pairs or the participants are being tickled by the experimenter or by the friend that came to the lab. So it's really manual tickling. Once you have so much variability in the methods from participant to participant and from a study to another study, it's difficult to draw conclusions and to replicate these findings.

So there is a possibility to do this in a more controlled way. This is what we do in my lab, the Tick Lab, where we are using robotic devices that tickle your feet. And we can control from an experimental point of view how the stimulus is going to be delivered on your foot sole. So how strong it's going to be.

It's going to be fast or it's going to be very slow. It's going to be on the right foot or on the left foot or towards the toes or towards the heel. So you can control parameters that are very difficult to control in manual tickling.

Tickling is also a bit of a social relationship, too. Have you found that there's a big difference in response when you're using some sort of robotic mechanism to tickle? I mean, people are still laughing, right? So clearly the tickle is still working. I had this concern before starting this research line because it crossed my mind. Maybe this really requires a certain social context.

But we find very vivid reactions of people to being tickled. People remove their feet from the robot because they're being tickled and they don't like it. It's not a necessary condition, it seems. There have been some attempts in the past to compare tickling

let's say, machine-driven tickling and manual tickling. But this was like by making people believe that in some trials they were tickled by a robot and in some trials they were tickled by a human. But actually, in reality, it was always a human tickling them. And that's satisfying that there were no differences in what participants, in the tickliness that the participants perceived. So, yeah.

both conditions were comparable. In this review, you were looking at quite a long history of all of these different papers involving tickling. And it was interesting that there's also a different sort of type of touch that isn't technically tickling, a lighter sort of touch. Can you talk about the distinction between those two types of touches? So another problem with research on tickling is that scientists mean different things with the word tickle. You can find a lot of studies on tickling

A kind of tickling which is induced by very light, slow touch applied on your body. This is something you can also induce to yourself. So if you take your finger and you try, you know, very lightly to touch your upper lip, after a while, it will give you the sensation that you're going to scratch yourself. It's like an itchy sensation that we call mechanically induced tickling.

On the other hand, what most people we mean with the word tickle is this forceful stimulation on certain areas of your body, like your armpits or your foot soles. And it's something that happens fast. You can really not predict it. And it's the one that elicits these sudden body movements and laughter, etc. Some people try to say these are too different. So let's call it, well, knismesis, more itch. And let's call the other one gargalesis, myelitis.

my review is more about the second one, meaning the one that is induced on certain areas of the body and it's difficult to self-induce. But this has added some complexity also in the previous research, what each author means with the word tickle. So if you're looking at studies that are just focusing on what you're saying as tickling, garglesis,

Is there a commonality between those body parts when it comes to why they might be more ticklish? It seems that there is an agreement that the foot soles and the armpits, the neck and the sides of the torso are among the most ticklish areas that are reported.

by children and by adults. And we are currently doing a study with a bigger sample size. And we are also finding that these are the areas that most people report as the most ticklish ones. Now, if there is something common between these areas that could explain tickliness, this is a very nice question, but we don't know yet. Because you could think that maybe these areas are linked at the physiological level, but it seems that this is not the case. So these are not areas that

are the most sensitive in touch because they have a high density of mechanoreceptors compared to other areas, there has been the suggestion that it might be linked to other factors besides physiological ones. For example, Darwin argued that these areas might be areas that we simply do not usually receive touch by others. So other people don't usually touch us there. Aristotle argued that it might have something to do with a cell.

skin thickness but actually the foot soles and the arvins are not areas that have very thin skin there so there have been no proposals across history another one that I find very interesting is the suggestion that the areas where you experience as the most thickest ones are the areas that

that you would like to protect because they are the most vulnerable in a fight? I'm thinking I would want to protect probably my heart more than the sole of my foot in a battle situation. Yeah. You talked to the interesting distinction where nismesis, this more lighter touch, you can actually induce it yourself versus gargalesis. Are there cases where you can induce that sort of sensation yourself or for the most part, it's just something that has to be administered externally?

Typically, it's difficult to self-induce Ghergalisi sensation. Now, there have been some studies, especially with Knie's methods, what we said before, so more itchy touch, that suggest that patients with schizophrenia experiencing a certain type of symptoms that correspond to hallucinations and delusions perceived similarly, experiencing

externally induced touches and self-induced touches, leading to the idea that maybe they can tickle themselves. Because the idea behind why you cannot tickle yourself is that when you are trying to tickle yourself, your brain can't predict how you are going to feel. It's not a surprising stimulus. So the brain suppresses our responses to this sensation because it's more important if you have limited the resources to dedicate them to external stimuli that might be more relevant for your survival.

And the self-induced stimuli, in theory, they are not stimuli that would harm you. There have been a lot of findings also from our lab that just touch without tickling. Features feel weaker when you are touching yourself, when you are producing a touch, compared to

to exactly the same touch when somebody else applies to your body. Oh, so not just for tickling, just in general. Exactly. Just the interesting thing about tickling is that with a touch, you do feel the touch on your body, right? It's not that you totally cancel it out. But with tickling, it's very difficult to induce these, you know, involuntary movements, the laughter. So it seems that it's all or none with the tickling. Either it's ticklish or it's not.

Have there been studies looking at people's brains during this entire reaction? Because it seems like a lot of the tickle is also the anticipation too. So what have people kind of found with that? There have been previous studies on what happens in the brain when you are anticipating tickling sensation or when you are experiencing tickling sensations. Again, we have to keep in mind that these are like with manual stimulation.

What it has been found in these studies are areas that are linked to sensations, somatosensory sensation, touch, movement. Also, you know, vocalization because you will start laughing, movement because you are going to maybe retract your foot or retract the area that is being tickled. So areas that are expected to be associated with tickling sensations are

And this is the case also when you are anticipating the ticklish stimuli. Have they looked at this for people who aren't ticklish? No, there is very little work on that. I have to tell you that this study that I'm also referring now about ticklish

what brain areas light up or when people are getting tickled, they were more focused on the laughter component. So these researchers are interested in what's the difference between laughter that is induced by tickling and other kinds of laughter. This is such a fun topic, but it seems like there's a lot of really cool neuroscience applications of what you can learn from this. It has a lot of implications that at first,

You don't think about it. There have been few studies that they study how infants or toddlers respond to tickly stimuli depending on their neurodevelopmental condition or age, how the reaction to tickle involve as a function of age. You can think about the evolutionary perspective of that.

So why would rodents have a reaction to tickly stimuli and great apes and humans, of course, and are there more species? And what does this reaction serve for? You can also think from a social neuroscience. So as we said before,

Why do we laugh if we don't like it? Or how you can differentiate from the reaction if somebody enjoys it or not? And how would the brain activity differ for someone that is enjoying and being tickled or not enjoying and being tickled, etc.? When you were doing this literature review, did it seem like there was more interest in this topic kind of in prior decades compared to now? Or what did that sort of look like? I would say that there has been a very...

scarce research over the last decades. I think also if you are studying something that is difficult to quantify and it's difficult to induce systematically, as a researcher at some point you might give up. What we are observing also in the lab is that we are inducing this sensation on the participant food cells and we are recording a lot of measures in order to try to characterize reactions of humans to tickly stimuli. So we are recording muscular activity,

to see if the participant moved their feet or moved their body in general when they received touches. But we also record physiological indices of arousal. For example, if your heart rate will increase, if you will sweat more, your skin conductance, if you will start breathing differently. Of course, if you laugh, we see facial expressions as well in videos. I really think that if you have good methods to elicit a sensation and good measures to quantify what's

what you are studying, research would go forward and more people would join the enigma. You touched a little on what your lab is focusing on right now, but what are sort of the broader questions that your lab's trying to address when it comes to tickling? We start from a very basic level. So first, we want to understand what makes a touch ticklish? What properties does it need to have? How can we characterize ticklishness? Okay, a person says that it's ticklish, the stimulation.

What physiological, neural, we also record brain activity, or behavioral responses better fit what the participant reported. Then at the same time, we're interested in your first point, when we laugh, do we like it? Or we just laugh as a reflex reaction. We are also interested in how the brain processes a sensation that should be matched between somebody else tickling you and you tickling them.

tickling yourself if it is with a through a device of course I'm talking about a well-controlled stimulus how the brain makes this cancellation of self-induced tickle sensation

Which areas are involved? What is the temporal profile of this cancellation? And maybe it would be ideal, I think, if we could also move that to clinical populations and try to see if what has been proposed for patients with schizophrenia, if they have something different in the way their brain processes stimulation. Thank you so much for taking the time to do this interview. Thank you very much, Megan. Thank you.

Konstantina Kilteny is an assistant professor and principal investigator at the Donders Institute for Brain, Cognition, and Behavior, as well as the Karolinska Institute. You can find a link to her review at science.org slash podcasts. Keep listening to hear the first installment of our six-part series centered on books about the science of death. This month, host Angela Saini talks with biologist Venky Ramakrishnan about developments in longevity research.

Hi there, I'm science journalist Angela Saini and this is the very first edition of this year's book series. Every month I'll be interviewing a different author, all of them speaking to some aspect of a single theme. This year we're leaning into the somewhat apocalyptic mood of the moment by exploring the science of death. My

My first guest is Venky Ramakrishnan, a biologist famous for winning the 2009 Nobel Prize in Chemistry for his research into the structure of ribosomes. I hope he doesn't mind me saying this, but he is now in his 70s and perhaps appropriately, his latest book looks at longevity, Why We Die, The New Science of Aging and the

the quest for immortality asks why we as humans are so preoccupied with living longer and whether new research really could help us do that. Venky, it does seem as though aging and even more specifically, immortality has become this huge topic of scientific and commercial interest in the last few years. How do you explain this interest and what made you want to write about it? Well, there are two aspects to it. One is that we've made tremendous progress

strides in understanding the biology of aging. And this is largely due to advances in molecular and cell biology. Along with that, we're facing a growing and increasingly aging population, by which I mean people are living longer due to medical advances, etc. But fertility rates all over the world, actually most of the developed world, have plummeted.

to below replacement rates. And so the fraction of population that's over 60 is dramatically increasing. So there's a real need to understand how aging works and can we ensure healthy aging in this population so that they're not just healthy, but also independent and perhaps productive. Now,

Now, coupled with that, there's an extreme end of this movement that wants to abolish aging and death altogether. They're not simply talking about healthy aging. I would say the majority of the community is about healthy aging, but there is this end of the spectrum where they would simply like to extend life much further. They don't like the idea that we might die at the age of 100 or 110 tops.

And there is that aspect as well. So as you say, in the last hundred years or so, average life expectancy has shot up. It was just around 40 years in the United States in the 19th century. Now it's almost 80 in the UK and Canada, even beyond 80. Does that suggest then that life expectancy is elastic? And if it is, how much further do you think we might stretch that?

Yeah, so there is a difference between life expectancy and maximum lifespan. So I should point out that even in Renaissance times, Michelangelo, for example, lived to be 89. And people did live into the 90s, even centenarians were not unheard of.

What the increase in life expectancy in the last 150 years or so has done is really addressed things like infant mortality, public health diseases, et cetera. And that got us from 40 to about in our 60s. And then there were advances in treating cardiovascular diseases, diabetes and cancer. And that's got us further. So we're now living to in our 80s, as you'd say, most of us. But the maximum life expectancy

is about 110. There are very few outliers who live beyond 110, and no one except one person has lived beyond 120. So that I don't think has changed really as a result of much of these advances. That I think is some natural limit of our biology, because lifespan for each species is a result of some evolutionary circumstances.

Right, okay. So maximum life expectancy is a very different thing from average life expectancy. Right.

One aspect of longevity research you do talk about in your book is how much money is involved here. I mean, this is a big business now. There are tech billionaires who have been willing to invest huge sums. And it does seem that there are researchers and companies ready to take that money and occasionally make very wild claims about what is possible when it comes to maximum life expectancy. You've been very brave in your book in calling out some of these people outright as charlatans.

Do you feel this is a field that at its edges has been corrupted? Well, money always tends to corrupt incentives. And I think a lot of aging research is funded by government

governments and by charities like the Howard Hughes Institute or the Wellcome Trust in the UK. Most of that research really is about trying to understand the biology of aging and how to improve health. Whether you can improve health without also extending lifespan is not entirely clear to me.

That is the assumption of much of the field. And they believe in this idea of compression of morbidity. So you stay healthy for a very large fraction of your life, and then you suddenly go into a decline and die. That is the sort of goal. But there's no reason why if you were to keep people healthy, you might simply postpone the inevitable decline, and you might actually have a slow decline. That's not entirely clear to me. The

The one argument against that are centenarians, super centenarians who live to be 110, typically have a very healthy life and then have a sudden decline. But it's not clear that what's happened to them is transferable to the rest of the population. Now, you talked about incentives. Well, you know, incentives do corrupt and some of the motives are different. For example, I suspect that some of these very

very wealthy people really are not just about healthy aging. They actually don't want to die. In fact, one of them, Brian Johnson, has publicly proclaimed that he wants to not die. That's his motto. And so there are a group of them who simply would like to postpone the inevitable. And

And how reasonable do you think then that is? Because you do sound very skeptical. I am skeptical in the short term. I don't think there's a physical or chemical law that says that our species has to die at whatever prescribed maximum lifespan is. But to change that would require really fundamentally altering

the aging process in us and whether that can be done safely and effectively and in a way that doesn't really affect us as humans. It is theoretically possible, but it's also theoretically possible to colonize Mars or even other galaxies, but it doesn't mean it's going to happen anytime soon. So I think aging is a complicated multifactorial process. And I

I'm much more optimistic that we will find therapeutics that will help us stay healthier as we age. But I'm not so confident, at least anytime soon, we're going to breach these barriers and suddenly everybody is going to live to be 150 or even longer.

So you talk about us as a species, and of course, a lot of biology is looking at other species and drawing comparisons. You do have this beautiful chart in your book showing how longevity in other species is at least somewhat linked to average body mass. It's not consistent, but there is a relationship. So larger species tend to live longer. Why is that? Well, there are some evolutionary reasons that you could imagine. So people, when they looked at variable lifespan in species,

assumed that maybe aging is programmed, that each species has a genetic program that causes it to die. But in fact, most evolutionary biologists don't believe that. They believe rather that genes are selected for other reasons, for fitness, by which I mean the ability to pass on your genes. And it just so happens that some of those genes that increase fitness also have the

side effect of aging later in life. But evolution doesn't care what happens later in life after you've reproduced. So there's no selection against aging. That's really the crux of it. So to get back to your question about the size, well, you can imagine each species has a limited amount of resources. Humans recently have overcome that with plentiful food supply and industrialized agriculture and so on. But for most of our existence,

Resources were a problem even for humans. And so you would have to then allocate resources to different processes. Now, if you have, for example, a balance between growth, maturity and reproduction versus maintenance and repair, they all cost energy, they cost resources.

if you're a mouse for example you would not want to spend much of your resources on ensuring that you lived a very long time because long before that you'd be eaten by a predator or you'd die of starvation

or a flood or drought or any number of things. So in a mouse, it's more advantageous to select for rapid growth and maturation. If you have a larger animal, then the equation is different. It does pay to live longer. You have longer time to find mates and nurture offspring. And of course, larger animals also have a slower metabolism. They have a larger gestation period. So everything is

slowed down in larger animals. And so there does pay for them to live longer. Now, there's an interesting, there are interesting outliers to this. And one particularly interesting one are bats. Bats live about the same, way about the same as a mouse, but can live 20,

times as long. There are bats that live for up to 40 years. And so if you ask, why is that? Well, you can imagine a bat can fly around. It can roost in the ceiling of a cave. So it's relatively resistant to predation compared to a mouse and also can forage over a much wider area. And so in evolutionary terms, it does pay for a bat

to put some of its resources into longevity because then it can reproduce over a longer period. So that's sort of the evolutionary argument for that. Of course, how each species does it is very different. They may have different metabolic rates, they may have different repair pathways, but those are all consequences of selection. Right, so given that this is an evolutionary question then, does that mean that there's not much medically useful to be gleaned

from studying the biology of particularly long-lived species? Or do you think there might be something useful there? I think there's always something to be learned from studying species that are different and outliers. I'm not sure that what you learn can be directly transferred. For example, in some species like elephants, they have many more copies of a DNA repair, a gene involved in DNA damage response. And that's supposedly why

Elephants, for example, don't get cancer at the rates that you might expect them to get given that they have so many more cells than a mouse. So you'll learn interesting things, but that doesn't mean that you'll be able to immediately transfer that learning or that knowledge to improving human health. But on the other hand, I think a lot of aging processes are universal. They simply occur at different rates in different species and the balance between

damage and repair is different in different species. So I think you'll always learn something, but it's not as direct as

people might have hoped. So within our own species, of course, there are huge differences in how people, how long people live. Is longevity then determined to some degree by our family histories, by our genes? You know, I'm often heartened by the fact that both my grandmothers lived very, very long lives, but does that necessarily mean that I will too? It doesn't necessarily mean that, but it certainly...

A good sign. I would say it increases the odds for you. There's an interesting study of centenarians done by Tom Pearls and his colleagues in Boston. And based on that, they have a website called livingto100.com. And of course, you know, it asks you all sorts of questions about your lifestyle and your

parents and so on. And one of the criteria is if you do have long-lived parents or grandparents, it does shift the odds in your favor. A study of twins in Denmark suggested that the heritability of longevity is only about 25%. I say only because actually 25% is quite a large number. It means there's a very significant genetic component involved.

to longevity, but it also means that a lot of longevity is due to life history and lifestyle and also sheer luck and accident. So you may be just lucky that you didn't get certain infections or you didn't get a cancer and you happened to survive. So there's a lot of various elements that go into determining longevity.

And one of the elements you do note in your book is that stress and hard living really does age us faster. And that's true even in some other animals. So you mentioned, for instance, the queen bee in a hive ages more slowly than the worker bees because she's essentially hampered by being kept deep inside the hive where she's safe, eating royal jelly. And this effect, you say, is visible epigenetically. Yes, that's right. So in fact...

If you look at the DNA methylation patterns in a

queen bee, they're actually different from those in the worker bees. It turns out our epigenetic patterns, one of the more common ones is DNA methylation. They actually are more correlated with our mortality rates than in our chronological age. So they're more a better indication of how old you really are in biological terms than your chronological age. Of course,

We've all been to high school reunions and we are struck by how different our classmates look. Some of them look almost exactly like they did when we were in school and others look almost unrecognizably old. And so that's just a fact of life.

Now, finally, I have to ask you this because I'm sure a lot of people thinking about this question will want to know if there's anything they can do to live longer. And one scientific finding that has grabbed attention in the longevity field is caloric restriction. What did you learn about that relationship between eating less and living longer? Studies in many different species have shown that caloric restriction does increase longevity and also health.

the calorically restricted older animals resemble much younger animals. And so there is one caveat, and that is the control is always animals that are fed an all-you-can-eat diet, which is typically quite rich. And so some skeptical scientists have argued that all this shows is that an all-you-can-eat rich diet is bad for you. And of course, we instinctively know that's true.

But nevertheless, it turns out that if you restrict your calories, it's generally better for your health. So that leads to the idea that maybe if you eat a moderate diet and don't overeat and eat a healthy diet, that that's likely to affect those same pathways that allow you to be healthier in aging. There are a number of pathways that have been identified and perhaps there are more that remain to be identified.

It's also true that certain drugs that inhibit those pathways can mimic some of the effects of caloric restriction, and these are being actively investigated. So that's certainly one of them. The other two legs in this sort of three-legged stool that I like to point out are exercise and sleep.

It turns out sleep does all kinds of things like repair and recycling that goes on when we sleep and thereby helps our metabolism and improves our health as we age. And exercise, of course, has a number of benefits, including regeneration, for example, of muscle and even of mitochondria. And so now that we understand some of the biology of these three activities, we

we know that they really do work and they work in a synergistic way. For example, exercise will also help you sleep and both of them will likely help you stick to a better diet.

And together, they will also reduce stress, which you pointed out earlier. So I would say these three things are probably better today than any therapy on the market. But I should point out that those three things also help with blood pressure and cholesterol. And despite my best efforts, I still had to go on statins and blood pressure medication. So you could argue that the goal of the aging research community is to try to go beyond

what we can do just simply by

these measures. So after doing all this research, has it changed how you live your life? Not particularly. I don't see what else I could do. I confess I have a sweet tooth and I need to control that. But other than that, I live a reasonably active life. I do like to get my sleep, although I think my wife complains I'm on the phone far too often, which I need to work on. So maybe I could

maybe there are things that could improve. And Dr Venki Ramakrishnan, thank you so much. Thank you. And thank you for listening. Next month, I'll be interviewing Susanna Monso about her new book, Playing Possum, How Animals Understand Death. See you then.

And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at [email protected]. To find us on podcast apps, search for Science Magazine or listen on our website, science.org/podcast. This show was edited by me, Megan Cantwell, Sarah Crespi, and Kevin MacLean. We had production help from Podigy,

Our music is by Jeffrey Cook and Wen Kui Wen. On behalf of Science and its publisher, AAAS, thanks for joining us.