167: Why Bats Don’t Age and Why You Should Care

Aging is usually linked to size, metabolism, and inevitable decline—but bats defy all three.

In this episode, Dr. Buck Joffrey speaks with Dr. Emma Teeling about why bats are rewriting the rules of longevity science.

The discussion explores how bats live far longer than expected for their size while avoiding cancer, immune dysfunction, and chronic inflammation. They examine how stable telomeres, enhanced DNA repair, and tightly controlled immune responses allow bats to age slowly despite extreme metabolic demands.

Watch the full episode to understand why bat biology is reshaping how researchers think about human aging and healthspan.

Learn more about Dr. Emma Teeling:

https://people.ucd.ie/emma.teeling

Transcript

Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.

    And if you were to, uh, look at species and predict how long they can live for, given their body size, the bats, you cannot do this. Most species a correlation is, is really one-to-one. So bats can live eight to 10 times longer than expected given their body size. And this is a minimum estimation of this.

Welcome everybody. This is Buck Joffrey with, uh, longevity Roadmap. And, uh, today, uh, we're talking about something again, uh, that will appeal to those of you who kind of nerd out on science, right? We're talking about bats. Right. And why are we talking about bats? Bats are a very, very interesting species. Um, you know, they carry like tons and tons of pathogens and, you know, it doesn't affect 'em, you know, they run around with all these, you know, COVID viruses and things like that.

In fact, there really is no sign of biological aging in bats. That's right. They're literally like if you catch a bat, um, when it's two years old. You look at its cellular aging, it's typically the same as like a 15-year-old bat. And they are, uh, an anomaly in, in that they also don't really follow this general rule where small animals with higher metabolic rates.

You know that they die quicker than, than large animals. So usually, you know, birds and mice, they die much quicker than like whales, right? So there, there's a lot of interesting things about them. Now, the reason, of course, ultimately we're not a show that is focused on, you know, bats and stuff like that.

But again, to reiterate, they don't seem to die of aging. And certainly there's no evidence of that right now in the labs. They die, uh, from predators, from starvation, from ecological changes, et cetera. And so if you think about the significance of that, I mean, it's pretty obvious, right? Look, there's probably something going on with these things that makes it so that, you know, they don't, um, accumulate the damage or somehow they are cleaning it up.

The answer probably lies in, in their immune system. The immune systems are, are, are very, very unique in that, you know, again, they're very robust to respond to pathogens, um, uh, or damage to DNA, but you know, they also don't create this sort of chronic inflammatory issues that that'll, uh, other mammals do.

If you can figure out like why that is, you can imagine the potential for pharmac pharmaceuticals and you know, other interventions that might be possible in humans, right? Again, if you could figure out, okay, well these pathways are why there essentially is no biological aging, uh, in bats, then potentially you can apply that to humans.

Anyway, again, it's a very sciencey, sciencey show. I think if you like this stuff, you're gonna love this. Uh, Dr. Admiring, uh, uh, from Dublin, who's kind enough to, you know, take the interview, uh, she's an expert in this space and, uh, tells a really interesting story, and we will have that interview right after these messages.

Hey, longevity enthusiast. It's time to take you to the next level. I've been fine tuning my longevity regimen for years, and I look better and feel better than I did a decade ago. In fact, my blood work is even better than it was back then. And it's all because of my data-driven regimen. And it's inspired me to create a course and community just for you.

It's called the Longevity Roadmap, and I urge you to check it out. If you're tired of your belly fat, tired of being tired, or just wanna optimize yourself for the next 50 years, visit longevity roadmap.com. That's longevity roadmap.com. Welcome back to Longevity Roadmap. Uh, today my guest is Dr. Emma Teeling, a world leading bat geneticist and full professor at the University College Dublin.

Hair research uses bats as natural models of exceptional longevity and disease resistance with the goal of understanding the biological mechanisms that slow aging and preserve health span, and also how those insights may ultimately translate to human aging. Uh, doctor, how are you?

I'm doing, uh, great.

It's great to actually talk to you. Great. It's so, it's getting dark and cold here now in Dublin, and I'm, uh, considering you in this glorious California.

That's right. Well, you were at Riverside for a while. I hear. So it gets really hot in Riverside. You're not, you were not only in California, but you were in, uh, you were in a very hot part of California.

So, um, well, let's get started here. You are an expert in, uh, bath. So what. You know, what drew you to bats as a model, uh, system for studying, I guess aging and longevity?

Um, it was complete chunks, so I was, I'd finished my, um, p uh, my bachelor science in zoology. I did a master's in L behavior and really I had thought that I wanted to try and study the evolutionary, uh, behavior of ecology of cats.

Okay. And I was trying to look for a PhD that was, so in Europe at the time, you're trying to look for a PhD. It fell up for a funded PhD and there was an advertisement saying, um, we're looking for PhD students who would like us to do the evolution of echolocation by sequencing genes in different species of bats and making evolutionary trees.

Oh, okay. And I said, oh my

good, I'll apply to that professor and I'll convince him that we need to study cats, not bats. So I did, I applied, I went, it didn't work out that way. Um, I, I applied for the position and it was very novel at the time because, uh, we were able to sequence little pieces of genomes of the nuclear genes.

I make evolution trees outta DNA sequences, which before they'd been made out of just anatomical structures. Morphology and doing this, we were finding very different evolution relationships. So I, you know, went up to Belfast to try and convince him to study cats. He, they all convinced me to study bats. I started my PhD and it was, it was a molecular biology PhD, so I was amplifying genes and studying the evolutionary adaptations that bats actually have, which EC location.

But within six weeks I realized I was. I was gonna be stuck with these unique species for life because of all the cool things they could do, and that actually looking at these unique traits, backs have evolved. They've evolved flight, they evolved echolocation. They are completely resistant to cancer.

They live for a ridiculously long time, given body size. They don't get sick with all these viruses. But to understand what was the genomic basis for these adaptations, we need to be able to look at the Gina. So I was able to link together the two things.

So from a comparative biology standpoint, you've mentioned sort of broadly, um, some ideas here, but what ways do bats age differently from most other animals or mammals?

Well, this was something that nobody really knew until, uh, we started to, to look at this about 15 years ago. So what we knew about bats was that. Some of the smallest MAs in the entire world are bats, and there's this kind of nearly a rule in nature. Small things, they live fast and they die young, right?

Think of a mag. Think of arou. Big things live slow and they live long. Think of whales, think of elephants, but bats are booking this trend. If you were to, uh, look at, at species and predict how long they can live for, given their body size, the bats, you cannot do this. Most species a correlation is, is really one-to-one.

So bats can live eight to 10 times longer than expected given their body size. And this is a minimum estimation of this. And this is based on these long-term marker capture projects where you catch a batter's baby. Put on some type of permanent tag, release it, atch it again and say, right, I caught this individual as a baby in 2010.

I've caught this individual now in 2020. That individual's 10 years of age. So all the backfield biology were doing this. So what we knew about bat aging was that it was different than other species because the back, the, the bat that for a long time had the longevity record was this male, uh, this bat was caught as a male in, uh, Siberia.

Little ring put on him, released, and he was cut 41 years later. So that individual was way older than 41. Um, no veterinary care, uh, with no signs of aging that we could see. And what was extraordinary, it wasn't the 41, but it was a fact that that individual weighed a third of a lab. Now we know that lab M and you can knock on a whole bunch of genes and they're not going to really live longer than four years.

But this is in the wild. So, and when you start to look at all these long-term marker capture studies, you find the majority of bats live way longer than expected given their body size.

So just to back up for a moment, um, you mentioned something which, you know, in general people kind of understand, which is smaller animals, higher metabolic rate.

Shorter lifespan. And then the, the converse of that, what's sort of the biological basis of that correlation with lifetime, with lifespan, so we can kind of understand like what trend that this is bucking.

It's got to do with the fact that metabolism can drive a much faster, uh, basically it's rate of living hypothesis, really high metabolism, uh, speeds up your, you're producing a lot more energy.

You're producing a lot more free radicals that cause a lot more damage that it potentially can accelerate the aging process. So this is all back then that you know, what actually is aging, what happens as we age? What breaks down? What drives it or cause it. So it's there the rate of living hypothesis.

Living fast. If you live fast, you die young. But it's not quite as simple as that. And also this thing, a lot of times your small animals will give birth very quickly to lots and lots of babies. So there's a cost of reproduction. So that's booking this trend somehow. They're living way longer than expected, given their body size, if he wants to say correct for human years.

So the longest lived bat has lived with the equivalent of 250 humane years. If we correct for body size, which is extraordinary. So what we wanted to do was we wanted to actually understand what happens with bats as they age. How can they somehow slow down expected aging? They have some of the highest metal, uh, metabolic rate of all mammals when they're flying, and they've worked out that they'll expend three times more energy over the course of the lifespan than a the similar size mammal that doesn't fly.

So flight's very metabolic, costly. So what we did, myself and my collaborators, we decided to study the aging process in backs and what we wanted to do. So we had to find a population of the longest live backs, and these were, these Myotis paths are called, and we need to know the age of these individuals.

Think about how you study aging. So in the lab, you know, the, the day an individual is born, the day they die, and you can sample in between. And what we need to do is when we find a pseudo population of these long lip bats that we knew the age, which meant that they all had to be captured as babies. The only way it can age a bat is capture as the baby when its finger bones are not yet fused.

Um, put a little microchip in, like you're putting a dog over a cat. Release it and then atch it again. This was the surefire way of knowing chronological age. So we found this population and we found this population beautiful, beautiful Northern France in Brittany with my amazing collaborators of PhD students, Basim, pma, Frederick Lan, uh, and all of this conservation grassroots organization.

And they had caught the entire population of these long lived my Otis backs in 2010. And they put these little microchips in all of them. And what happens is that the females come back to these same churches every year to give birth. And if you're born in this church and you're female, you come back to this church, which meant that we can catch them year after year after year after year.

And we've been doing this for 14 years. What we do is we take a little bit of blood. We take wing punch, little bit of tissue, we will take a buccal swab, we'll take an anal swab, we'll measure the bats. And we studied the, the, these individuals as they age, year after year after year. And what we wanted to ask was, well, what happens in bats as they age?

Do they show that same level of, um, breakdown as we would? And we want to look at these hallmarks of aging. So there are a whole bunch of different molecular assays that are designed to work with humans or mice. So for example, telomeres. So if you remember what they are, those tt a, g, G, those protective caps at the end of our chromosomes that shorten every time our cell replicates because you can't add on, uh, ides to the phy primate.

So it's just a, a, a, um, a biochemistry problem really.

So telomere shortening, right? A frequent, frequently sided, uh, in, in larger space.

Yeah. You speak to this, that this was the mitotic clock, and that if you had along telomere, you're gonna live much longer and that you, you how long you could live for was gonna predicted by your tel.

And so, and if you wanted to rejuvenate a mouse, you'd get it to express telomerase. So the enzyme that it allows your germ cells, your egging, your sperm, uh, make sure that the telium don't shorten. Um. So we wanted to see, well, in these long-lived bats, do they, what's going on with their tumor ears? Are they shortening?

Are they not shortening? Do they have a way of maintaining them without getting cancer? So, what's known about bats when you study these that there's little to no evidence of species getting cancer. You don't see tumors, you don't see any of these in these, these long, long term studied populations. Uh, sometimes you may see tumors in some of the captive fluke backs, but that potentially captivity is not so good, but, but it's high.

You don't see, so they don't seem to get cancer. So the problem is, if you wanna maintain telomeres, which will keep you young, allegedly, you have to express telomeres or disease alternative telium re lengthening, and that is what cancer cells do. So we wanted to ask a question first of all, in bats, do the telomeres shorten with h.

If they don't, how are they maintaining them? So we did this, so we caught all these known aged individuals. We did this, we used this, this QPCR method designed to work on humans to be able to work on backs. And we looked at relative lib lens. So we looked at young, middle aged, and older bats to see what would happen.

Because in us, in chimpanzees and many birds, uh, sea lines, everything tillary shortened with age. And what we found was extraordinary. Our longest lived bats, telomeres do not shorten with h they just dumped. And we initially, we started the, the, the, the study and ah, you've got it all wrong to my PhD students, go back in there and try and do it again.

And what we found was that we had these, my oldest mys, the longest lived bats, we were able to study the other, uh, populations of bats. 'cause we developed the methods. Other people came forward, said, Hey, listen, let's work with these horseshoe bats. Let's work with these short-lived molasses bats. What are we gonna do?

So what we found is very interesting in the longest lived bats, which are the myotis bats, their tel do not shorten with age. So they just, they're able to maintain them throughout their life.

And that's without higher expressions of glomerate or what, what's, but

this is, this is what we're kind of investigating.

So this is still the, the unknown part. So the telomeres are not shortening with age and. We then looked at, we also took blood and we sequenced the entire transcriptum, and we wanted to see is would we find telomerase expression? Is it gonna be higher, is it low? Looking at kilometers expression, it's very, very low no matter what.

Um, and so it was a very difficult thing to look at when you look to just transcriptomes. So there was work done with our collaborator, Vera Gober Nova in Rochester, and they were able to, they grew basically bats in a dish. So take that wings, grow the cells in a dish, and they look to see if we did these assays, could we see that telomerase was working?

And it looked like it was. The other cool stuff that Vera and her group did was they went, okay, uh, so looks like they are expressing telomerase, but is it easy to make bat cells cancerous and we can knock in and knock out different oncogenes or tumor suppressors? And actually it's extremely easy to make bat cells malignant, but in the wild, they're not showing this.

So what are they doing? And so this was something that we're very interested in. So we're exploring that. Are they somehow able to express mase, but main, um, find a way to be able to regulate the development of their tumors so they don't get them? 'cause they have another surveillance method potentially.

So they have the rejuvenating effect of telomerase without the malignant effect because they have evolved another mechanism. And this is what we're looking at at the moment. We're trying to look at is it some type of immune surveillance? Do they have much better checkpoints in their cell cycle regulation?

They never let their cells become malignant. Do they have a higher expression maybe of. P 53 or some of the gatekeepers of yourselves. So this is where this kind of research has gotten to at the moment. This is one exciting part of this. Yeah.

Yeah. What, what do we know about, um, we, you know, when you think about some of the, the, uh, reasons that we believe that aging concurs, a lot of it occurs not only with telomerase.

There's, you know, damage to, uh, DNA. There's, uh, damage to what we, we know as the epigenome and, uh, you know, epigenetic drift and all, all these other things that we, we frequently talk about in the human. We start talking about human aging. What do we know about those things with in the bat world?

So this is a question we asked.

So as we age, as humans age, you find this dysregulation of, um, the expression of our genes. And there's this kind of increase in inflammatory transcripts. You'd find your DNA repair starts to decrease, your inflammation starts to increase and not able to balance it. So we wanted to ask the question within these long-lived bats, what's going on with them?

So we took a little bit, we took blood. From, and also you can only take, uh, less than 140 microliters. Remember, these guys are no bigger than 27 grams and they're the big ones that we're working with. So we, we took the blood and we sequence the entire transcript. Don't ask that question. Um, again, what we found was another extraordinary insight as these long lived bats age, they increase your DNA repair.

So it goes up, they, uh, find a way to be able to decrease inflammation. So they seem to have this very balanced inflammatory and anti-inflammatory response. They seem to have us do both, so they seem to be able to make, there's, there's, um, an increase in inflammation, but there's also an increase in anti-inflammatory markers.

So they were able to keep that balance. They're very difficult things that, so they, they show a complete opposite in some of these particular pathways. So DNA repair and cell cycle regulation. Much more tightly regulated and increases with age and inflammation stays low in bats as they age. There are two major things that are different in bats than in humans.

Sometimes we think about the changes in, um, you know, the actual epigenome and, and epigenetic drift is, is part of what is causing a lot of the, you know, chronic inflammation issues. So, so you're saying that they somehow are able to. Uh, you know, not have some of these epigenetic changes and, and therefore, uh, less, uh, immune dysfunction.

I don't know about the epigenetic changes. So what I'm saying is that when you just look at the genes that are expressed, there seems to be an increase with expression, with age, and maybe they're experiencing more, more damage. So they're able to repair it better, so they're able to fix things better.

They have a a different expression profiles, so maybe they're a bit more sensitive to DNA damage and they. Remove it. So autophagy also increases in backs much a higher level. So they either remove it or they're much better at repairing it. And so that's simply about are they more sensitive to this damage?

Are they better able to, so they don't show the dysregulation in the DNA repair. So that has had to be evolved. They have had to evolve ways to maintain it with time. But back, back under the, the idea of this, the methylation signature, and so. We did work looking at, when you look at those methylation chip, where you could age people, so you know the Steve Hobits methylation ship, for example, and you look at right across you, so you are able to age bats looking at a certain rate of those sites.

Like you can age humans, like you can age other species. What's really interesting is that the really long-lived baths, their clock ticks at a much slower rate, so they're not showing the same level of methylation. Uh, dysregulation that we would, that we are experiencing, so that that's some of, maybe they're finding a way to maintain, I call it factory settings.

So that seemed to evolve ways. I mean, now what causes this? Why did they evolve? So let's, let's remind ourselves what are they doing? They maintain their genome. They're able to repair the damage or remove the damage. They're able to, the really interest, they're able to maintain this, this immune function.

They do not become inflamed as they age, so their immune system's kept under control somehow. Um, they're able to, their, their telomere in the longest lived of the lung that telomeres are maintained. But long le bat, don't all do this. So these are kind of unique things. The question is how are they doing?

Why are they doing these things?

And the, it sounds to me like one of the, I mean, the primary theories is that they have different types of immune function. And, and this is an interesting thing with bats too because you know, there as an aside, they're, they often carry all sorts of horrendous viruses. Um.

And could, could you comment on sort of what we know about the immune system a little bit more, um, that allows them to sort of, you know, carry these viruses, uh, carry all these pathogens yet not get sick, and, and, and how that may lead into what we're talking about in terms of differences. Uh, you know, some of the hallmarks of aging.

Absolutely. Um, so I, I'm one of the family directors of Bat one case. We're this genome sequencing consortium where we wanna sequence the genome of every living bat species to these exquisite reference, reference quality genomes so that we can align them all up, compare them with us, and look for instance at immune the immune genes.

So we did this, and what you do when you find this, you find that. There's really different evolutionary selection, pressure acting on. We can see in bat genes b immune genes, for example. They're missing this, they're called their pie in genes. They're missing these inflammasome genes that all of their mammals have.

Bats are missing them, which means that they, and they have moderate, they had. Point mutations and sting some of these immune genes that allow them, you know, for example, sense DNA. So if the, the immune system would sense sickle cell DNA, for example, using this pathway. The bats have changed it. They look like they have this expansion of these, um, really, really hardcore antiviral gene.

They have these constant inflammatory, um, immune stimulating genes. These interferons, they have these genes. Um, they have lots of different cough with them. So what you, what you see in the bats when you look at their genome, this is just first looking at the DNA. You see loss of certain genes, loss of inflammatory genes, expansion of a novel type of antiviral gene system.

You see expansion of certain anti-inflammatory genes. Then when you actually look at the expression in the immune cells that we were able to isolate, make macrophages from these, these are wild bats, we were able to do it. And you see a very different expression in how these bat immune cells respond to the stimulated infection.

So for example. So you get a bat macrophage, so the kind of frontline of your immune, uh, uh, your immune response and you'll knock in say LPS or poly ic, which are mimicking bacterial or a, uh, viral infection. And then what we looked at was just the immune cytokines. So you'd look at IL 10, which is anti-inflammatory.

You look at IL one beta, which is inflammatory or TNFs inflammatory, and we compare it with megs. What you saw when we mimicked this infection was that at the very beginning, the bats meant this really, really aggressive antiviral response. Really, really inflammatory. The mice dumped, it's a bit lower, but then the bats equally mount at equally aggressive, if not more so anti-inflammatory response.

So IL 10 goes through the roof, and so. Toward after 24 hours at the end of the infection, what you'll see is that the mice are really highly, highly inflamed. They cannot resolve their own inflammatory response, but the bats have neutralized the pathogen and then neutralized their own immune response.

That's amazing. So if you think with SARS cov to two and you think about, so using these races, I think that they're looking at IL six to IL 10, for example, in hospitals to work out whether or not patients would need to go on a ventilator. If your ratio of inflammatory to anti-inflammatory cytokines look more like a batch, then a mouse, you work on the need of, uh, a ventilator.

So they seem to have evolved ways to be able to both deal with the pathogen and then deal with themselves. And it's not just a more, more

responsive immune system. In in, in, yeah. In a nutshell, what you're kind of saying is you have this very, very, you know, aggressive, more aggressive than typical initial response to whatever, um, you know, whatever insult there is.

And then once it's taken care of to be able to go in reverse almost, and. Make sure that, uh, you don't continue to damage the, the cell of the actual species itself.

And the question is, we say the word more aggressive, but maybe it's not more aggressive. Maybe it's just more nuanced. So, you know, we have the pie that why would they lose this inflammasome and then evolve a different way of, of doing what it was supposed to do.

So this is back end of the question. So they're a, they have tweaked their immune response to, to get it just right for the pathogens. So for, for, for the likes of, of, of, uh, coronaviruses, um, potentially for Marlborough, potentially for these very scary ones. But other pathogens can kill bats. So in the US you know, with white nose syndrome, a skin fungus is wiping out certain species.

So their immune responses evolve to deal with certain pathogens, but not all. And in some way, this is where studying many different species have different adaptations, different pathogens, but give us lots more insight.

You know, when, when you talk about various interleukins and that kind of thing, are, are those the same?

Um, I mean, obviously you have different quantities and they're being expressive at different times, different quantities, but are they the same?

It's, it's a very good question. And so when you go and you look at the, the, the, the DNA and you look at the protein structure, yeah, they're pretty much the same.

They're doing the same thing. Um, you can make, uh, we can, you can use antibodies, human antibodies that can sometimes map on to, to the, the, the appropriate. Um. Bash molecule, but it's not always the same. But broadly battered mammals we're mammals, so pretty much they can do the same function. So what we, what, what my collaborators of mine, lympho group in Singapore and Mattan, they found that this, this bash slightly different immune gene this.

Ask two one, ask two. And they were able to knock it into a mouse. And so that means that all of these, because we're all mammals, you can interchange these different genes and different proteins and they will, and they did serve an immune function, so I would say yes. Um, but they've tweaked them differently.

It's like there's slight differences, but in all humans there's slight differences. It may be a base base change here or something else that makes a function better.

And and do you think those slight changes, I mean, are those, what are potentially, what are making them more efficient?

It's a brilliant, brilliant question, and I have spent years looking at the slight changes.

Um, and I'm not sure, so if that change, that single point mutation is maintained in all bats and the other foods. And I would say definitely. So we'll see. We, we will see situations like that where every species of bat that we've looked at now we have all, we've all, all the families represented, we have over, you know, two, 300 genomes I would say yes.

Potentially that site's very interesting, but I also think it's how they regulate their actual proteins. How do they regulate the expression? When did they switch it on? When did they switch it off? What excites them? So it's that fine scale level of expression differences. And what I wanna look for is a regulat.

And so is it what, so this is why you need to look at, at the actual cells and how are these, how, what happens in real time? Um, do you find things get switched on, get switched off at different time points? We need to look at the enhancers, the promoters, the microRNAs, for example, the master switch that may drive all of this.

Now for the single point mutation, that's gonna make us easy. But, um, but it's harder to drug humans with a single point bat mutation. But if it's simply a different regulation of when or when you switch on or switch off an immune response, this, I think we can drug.

How do bats die in the wild? It sounds to me like you've got.

I mean, you're in, you're finding in, in some of these bets that basically didn't age right? So there must be some sort of aging process that ultimately overwhelms them. Uh, what, what, how do they die?

It's a very good question. People ask me this a lot. So what you see when you look at their survive, their survivability, that there is no age related mortality in bat.

So a bat at one has the same chance of dying your bat 30. What kills them and what we see are predators. Owls.

Yep.

Owls cause me so much trouble. My owls coming in, snakes, all these things I want to eat them. Um, hunger. So cold springs will do, the environment can kill a. So, uh, in, in Australia, see when it's too hot, they're all dying.

In Europe, you see that if you have a very cold, wet spring, the babies, the females won't be big enough. The babies won't get big enough to survive the hibernation. So food shortages. So environment causes problems, predators cause problems. Um, there are certain diseases that will kill different species. I think Vulu virus is not good for certain bat species, but really the major things that I think are killing the bats at the moment, they're us.

They're habitat. They're predators and, and it's, it's, it's accidents and starvation.

So if I, if I understand you correctly, bats don't die of age-related disease.

Not that we've seen.

Yeah, that's, that's pretty profound because even if you look at. Some of the longest living species that we know of.

Obviously they eventually die. These whales may live hundreds of years, but they, but they ultimately die. So it's not just slowing things down, but in, in fact,

the other thing is, remember, we're sitting in wild populations, right? So if they die, we're not going to see them. So, um, we see them year after year, June, some of these popul C for 60 years, and really they're not seeing any of those.

You don't have an old B and you don't have these other things. You don't have, you know, a bad fur. Um, when we are catching them, we know their age. It's, it's sometimes I'll, I look at this bat and I go, oh my goodness, their teeth are all destroyed. Uh, they look wrecked. They look, that must be an old bat, you know, and then we scan it and, oh, she's two.

Yeah,

she just

was a silly, a silly bat, you know, eating stones rather than beetles or whatever. So, so in captivity you'll see, so you'll see some of these bats that do look gold, some of those fruit packs. But then again, they are in captivity and I don't believe her husbandry is good enough. So it's not a real example, but we haven't seen Annie age related mental.

The other thing that we have to think about is they echolocate. So what's the first thing that goes as we age? So we're all going to be, half of us will be, or 80% of us are supposed to be deaf by the time we're 80. But they have to be able to maintain their hearing and their exquisite hearing right up until their forties, fifties, however long they live for, they're going to die.

And so the long, so the individuals that we catch in the wild that the longest lived individuals really, really hold that genotype for longevity because they've survived all of these accidents and so forth. You take it with a pinch of salt. 'cause you know, people ask you for, are you sure you're able to really, really see what happens as they really do eventually get, you know, live much longer than would, than their maximum lifespan that's recorded.

We just work with what we can, but we still don't see it. And so

if what you're saying, um, you know, turns out to be, you know, accurate, there should be 500 year old bats flying around.

We don't see them. And so then, then again, I, no, no, I'm not gonna live till I'm 500 unless we, unless we really find something fast and soon.

And so you, you've also, this was the other thing that you know, well, how long can bats live? People always ask this, well, they live, they seem to be living as long as we're continuing these marker capture projects, so there is a maximum lifespan. Right? There has to, because in, in these long lived in, in the Horseshoe Baths, for example, that meets really for 60 years.

By one individual. He just won a, a prize from the king. The brilliant Roger Ransom has been studying this population really on his own for over 60 years. They're maximum licensed 30, so they must have to age. They die somehow. Now, maybe all the accents catch up or maybe there's something we haven't uncovered yet, but no matter what, they're the aging, their expected aging has really, really slowed down.

Yeah. Um, how do you take such a unique, uh, organism with a different. You know, set of rules and you know that, that it's not clear exactly like, you know, maybe there are some point mutations in those, uh, interleukins or whatever. How, how do you, how do you start using some of this information? And maybe this is not really your area, but I'm just, when you start trying to apply things to human aging and application, whether that be through pharmaceuticals or.

Understanding better, you know, how to increase lifespan or health span in humans.

Um, that's ultimately the goal of where we want to go. And so right now, a big E or C grant with these collaborators in Singapore and Germany. And so the idea is that we, we, we wanna study the backs. Find the, the regulators, the master regulators are allowing them to slow down the aging process, whatever it is.

And we're, we're looking at their DNA repair. We're looking at the ability to remove their damage, for example. Um, and also regulators that allow them modulate their immune system. What we are doing with these, we we're in the process of putting all the data together, identifying we have some, some interesting candidates.

We need to knock them into human cells, for example, and show that. That has its functional effect that we say what? That, that it's happening. We need to knock them into a lab mouse and show. Actually, if we knock in the, this regulator, uh, this will allow this mouse live longer. This will allow this mouse not suffer the same stresses of aging.

We're locking them into, um, worm. To see elegance. 'cause if you have a single point mutation, see elegance can make it live 10 times longer than what we expected. So these are all ultimate targets, but we compare all the time what we're seeing with the different bats with our human cells. And so ultimately we say about this, this particular pathway, if you mod mod, if you modulate that pathway in the way the bats are being modulated, that this will allow a human cell not age as we would expect.

Then what that means. Say, well, okay, what is this? What is that regulate? What is it a micro RNA or is that this a different per, is it a different expression of this protein at a different time? Is it a dampening of a mass regulator like this? The dream activated, which, which dampens controls? DNA repair.

Then we went, we were thinking, well, we're gonna try and find some, so, so now you can use lots of new ways to be able to look at these small compound biomolecules. That potentially can interact with that pathway that will create drugs. And then we need to think, well, will that be useful for humans? That's ultimately where we would need to go.

So I know a lot, a lot of the, in the longevity field, there's a real push right now to come up with drugs that can, or, or small compound molecules that can actually go drug a pathway. And so what we're simply doing is we're help using the BA, our knowledge from the bats to help us find a better roadmap.

To be able to say, well, these are the pathways that are the most important. These ones really aren't, and this is what we should focus on. And then by looking at these, the, you know, X vivas, such the human cell lines and showing that it works in humans and the human cell lines, we're gonna make the assumptions gonna work in human humans.

We'll also have knocked them into a mouse, and that's where we need to get it.

Now if, if you were starting, uh, and you got to choose any pathway that you know about right now as your first target to try to try to translate some of this work, what, what would that pathway be?

Eh, that's a great question.

It's one I'm asking to all our team at the moment, the rice, you got 10 million, what are we gonna do? I could go with lots. I've, I've got lots of different ideas, but I definitely think we need to start looking at the immune system. And there are certain. Genes that have been knocked out bats, genes that have been like ISG 15, for example.

We just published a paper. It was led by Michael Hiller and Aria Edna. Um, that, that there's a tweak in this in the bats. And this is a, this particular gene is really, really important, but a lot of the COVID, sorry,

which, which gene was that?

It's an immune gene. These IT 15.

Okay. Means

gene 15, I think would be somewhere where we could look it.

So the papers, just, the paper was published in nature in January.

And that code's for what?

Immune stimulating Gene 15, I believe. Okay.

Okay. Whatever that is. Okay. Alright. Alright. Something that does

that with the immune system. Um, but it, but it's not just that. So, so that was one gene that we were able to find, but there's a whole entire pathway of how the bats are recognizing viruses and how they are dampening their inflammation.

And I think the reason why I think it's a good idea to look right now at, at their inflammatory. Pathways is because that's right at the center of all of these aging processes. And so also I think that this is the change that had to happen in bats due to the acquisition of flight. So people ask, why are bats doing all these things?

Why? Why would they evolve these mechanisms? So let's think about flying. You know, they're the only mammal that have true self-powered flight. Flight is extremely metabolically costly, and they will produce, they produce loads and loads of these three radicals breaks up the DNA. So they've had to evolve mechanisms to be able to not become constantly sterily inflamed every time they fly.

And so they've had to fall away to either remove the damage because Thera will break up the DNA. It'll look like it's a pa. It'll look like it's a bacteria. The immune system has to not get overexcited. So they've had to evolve ways to them. This means that they had to modulate their immune system to be able to deal with this.

This means they had to find ways to repair that DNA or to better to remove the damage. Um, and what that then does in turn all those different pathways are the major drivers allegedly of the aging process by the bats tweaking these adaptations, most likely stemming from their immune response. They now.

Live longer 'cause they don't suffer the same effects of this inflammation driven aging. But also they can live with all of these pathogens because they deal with now pathogens in the same way. So what kills us with an infection is our inability to put the throttle on our own own immune response.

That's what sepsis is. That's what unfortunately people who, who ended up dying of, they weren't, you're not able to regulate your own immune response. People from, that's what happens. So they've have, they. Because they have to evolve the adaptation of their immune response. Therefore they are able to deal live with pathogens as well.

So if I was putting my money on it right now and I have lots of things I'd put money on, but it would be in this pathway here that we should start looking or continue looking. 'cause we have a whole bunch of candidates that people have been working on.

Fascinating stuff. Uh, Dr. Emma Teeling, uh, university College, Dublin, thank you so much for being on Longevity Roadmap.

If we, uh, wanna learn more about this kind of stuff, any resources, uh, people curious to kind of just learn a little bit more,

look me up on LinkedIn. Um, type in bats into Google Scholar. You'll find lots of stuff. You've got Ted Dogs. Come look up the, and also there's. Huge C, so bat one K, there's, this is a community of all the bat researchers do lots of different things, genomics, people are just interested in.

We're always looking for other people to come and join us, so there's lots out there.

Thanks so much for being on the show.

Thanks, spark.

Thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical advice. Now, make sure to include your physician in any medical decisions you make, and also, if you're enjoying the show, please make sure to show your support with the like, share, or subscribe.