Can Animal Super-Agers Teach Us Their Secrets?

Some animals seem to defy the rules of aging. Understanding how they do it could help us live longer, healthier lives.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:01Flora Lichtman?

  Hey, it's Flora Lichtman and you're listening to Science Friday.

• 0:07Flora Lichtman?

  Today on the show, looking for the fountain of youth in the animal kingdom.

• 0:12Speaker 01

  It would be like an Olympic athlete, basically, that runs casual triathlons every day, living insanely long time, like 200, 400 years.

• 0:23Flora Lichtman?

  Some animals have a very different relationship to aging than we do. They don't get cancer, they never go through menopause, and they live these absurdly long lives. For instance, one bat species can live for over 40 years. That may not sound like a long time, but that's like nine times longer than you'd expect based on their size. For comparison, if we aged like these bats, we'd be living for hundreds of years. And these bats aren't the only superagers. There's a whole menagerie of them. So what's their secret? And can we learn anything from them that might help us live longer, healthier lives? We're talking to two scientists, Dr. Vera Gorbenova, a professor and biologist at the University of Rochester, and a trailblazer in this

• 1:08Flora Lichtman?

  field who's been studying aging for over 20 years, and Dr. Juan Manuel Vazquez, a biologist and assistant professor at Pennsylvania State University studying how superaging evolved, mostly in bats. Vera, Manny, welcome to Science Friday.

• 1:22Speaker 02

  Thank you for having us. Hello.

• 1:24Speaker 01

  Yeah, thank you.

• 1:26Flora Lichtman?

  Let's start with these bats. Tell me a little bit more about them and what makes them unusual.

• 1:31Speaker 02

  Yeah, bats are very amazing. There are thousands of species of bats. But among them, there are many bats that, as you just mentioned, live much longer than would be predicted based on their size, because generally, animals that are larger, they tend to live longer. So bats are clear exception. If you plot, for example, 200 different mammalian species on a graph, so... Longevity versus body mass, so bats would be off the line.

• 2:06Flora Lichtman?

  They're off the charts.

• 2:07Speaker 02

  Yes. And in addition to this long life, they're quite healthy. And when they fly, their metabolism gets very high. So sometimes people would say, oh, well, there are some species that live very long time. For example, Greenland shark is very famous. They can live for hundred years, but they live very slowly, which may not be the lifestyle humans would want to adopt. Swim, they eat maybe once a year, swimming in cold water. But that's not the case for bats. When bats fly, their metabolism is also off the charts. But yet they can kind of compensate for it and not develop

• 2:52Speaker 02

  diseases that would be linked to high metabolism. So that's very.

• 2:56Flora Lichtman?

  So they live long and fast and healthy.

• 2:59Speaker 02

  Yes, exactly.

• 3:00Speaker 01

  That's, I think, like, the thing that's, it's really important to contextualize, right? Like, the world record holder is Brant's bat, which was caught as an adult, tagged and released, and then caught forty two years later. Uh, that bat was active out in the wild, hunting in three dimensional space, remembers where to go to find prey, remembers where to go back home. So imagine knowing casually, without any GPS, how to go from Rochester, New York, to, like, State College, without looking at any, like, interstate maps, right? You have to travel, like.

• 3:36Flora Lichtman?

  I can't get to the gas station in my town, Manny.

• 3:38Speaker 01

  Exactly, right? And so, like, somehow not only do they do know how to do that, they know how to do that while flying, while, like, all the aerobic activity necessary for flying. Like, there's so much that's insane about that physiology. And then when you throw into it, like, the, yeah, they also live a ridiculously long time, right? It would be like an Olympic athlete, basically, that runs casual triathlons every day, living insanely long time, like two, four hundred years, as we said.

• 4:07Flora Lichtman?

  Vera, when we talk about aging, what are we talking about on the molecular or cellular level? Like, what is biologically happening when we age?

• 4:20Speaker 02

  Well, this is a very important question, and there are many different answers to it because aging is a complex process. Many things deteriorate over time. So if we think about aging at the cellular level, not only we accumulate mutations in DNA that can be linked to cancer, we see various types of damage that accumulate to proteins, lipids, DNA. There is also loss of organization of chromotines. Because if you think of DNA as a very long thread that contains the words in it for making proteins,

• 5:03Speaker 02

  this thread needs to be packaged in a certain way, otherwise it will get all tangled. So it is organized in a very specific way in young cells. And there are some regions that are more open, and these are the regions that are more active and they produce RNA and make protein. Then there are other regions that are more tightly condensed, and they may contain even some undesirable things like transposable elements that are virus-like parts of our genome, so-called dark genomes.

• 5:34Flora Lichtman?

  The dark genome, yeah.

• 5:36Speaker 02

  But as we get older, what happens? Those regions that are open start to close a little bit, and those that are closed, like these transposable elements, they start to open up, and these parasitic elements now become more active. And that affects how the cell functions at every level.

• 5:56Flora Lichtman?

  Vera, I know you've studied a number of different animals. You just published research on bowhead whales. Why are you interested in these whales?

• 6:04Speaker 02

  Well, a bowhead whale is amazing because it is the only mammal that lives longer than humans.

• 6:14Speaker 02

  Bowhead whales can live 200 years and probably longer. This is very remarkable to maintain their bodies in perfect order for two centuries.

• 6:27Flora Lichtman?

  They don't get cancer?

• 6:28Speaker 02

  Yes, there were no documented cases of cancer in bowhead whales. And another aspect that makes them extremely interesting, along with other large whales, is their size. Because statistically, the more cells are within the body, the more likely would be the chance of developing tumors. So it should be proportional to the number of cells. But whales are extremely large. They're 2,000 times larger than an average human, if you're just thinking about body mass.

• 7:04Speaker 02

  But they are not 2,000 times more likely to develop cancer, which means they evolved adaptations to resist cancer that we humans don't have.

• 7:15Flora Lichtman?

  And you found, it seems, a clue into this.

• 7:19Speaker 02

  Yes, so it was interesting because originally our hypothesis was that whales probably are similar to another very large organism that was studied. So this concept, by the way, of larger organisms not developing cancer despite statistically being likely to do so is called Petrus paradox.

• 7:42Flora Lichtman?

  Yes, and we've talked about it on the show because elephants are a test case, right?

• 7:48Speaker 02

  Right, so what elephants have, they amplified.

• 7:52Flora Lichtman?

  Wait, stay with whales, stay with whales for us.

• 7:54Speaker 02

  Well, I must say a word about elephants so that you will understand.

• 7:58Flora Lichtman?

  Okay, okay, okay.

• 8:00Speaker 02

  Because in the elephants, they enhanced the way cells are, the surveillance, so like eliminating cells that are damaged. So that is the strategy for elephants, bad cells get rid of them very quickly. Uh, and that was our hypothesis for the whale, but this is not what we found. Uh, we found that the whale enhances maintenance. They just don't accumulate mutations as fast. And when they are faced with DNA damage, they deal with it much more efficiently. They don't kill their cells very readily, but they maintain their cells. Like they don't let things deteriorate to the point that it's necessary to eliminate the cell.

• 8:45Flora Lichtman?

  How do they do it?

• 8:47Speaker 02

  Well, they have a um very high levels of a protein called C I R B P or cold-induced RNA binding protein. And what we found is that this protein promotes more efficient DNA repair and it protects from mutations. So we humans also have this protein, uh, but we make very small amount of it. And whales make maybe hundred times more.

• 9:14Flora Lichtman?

  Hmm.

• 9:15Speaker 02

  And as the name suggests, it's cold-induced. So it has something to do with cold and whales live in cold. But we hypothesized that evolutionarily, uh, they upregulated this protein first to deal with cold. But then it was also co-opted to help DNA repair. And this way whales enhance their maintenance strategy. Uh, because I'm thinking the strategy of an elephant is good. Uh, but maybe up to a point, if you plan to live more than hundred years and you're eliminating cells very readily, you may deplete your stem cell resource.

• 9:51Flora Lichtman?

  Run out of cells.

• 9:52Speaker 02

  Yes.

• 9:54Speaker 02

  So it may be for the life spans that exceed two hundred years. Well, you need a different strategy. You just need to prevent these mutations in the first place.

• 10:05Flora Lichtman?

  Did you, did you test putting this protein or or sort of higher levels of this protein in human cells?

• 10:11Speaker 02

  Yes, that was the most exciting part. When we put this protein in human cells, it improved um the way cells repaired breaks in the DNA.

• 10:22Speaker 02

  So they became about twice more efficient. So just with one protein, uh, which for me was the most exciting finding because it means there is room for improvement in human DNA repair.

• 10:35Flora Lichtman?

  Hmm.

• 10:36Speaker 02

  For many researchers, um, human DNA repair seemed like something like, okay, we are given it, we cannot make it any better. Uh, if we even try, we can change the balance between different repair proteins and things would get worse. Uh, but what this study demonstrates that we actually can make it better. And that gives hope, uh, for longevity and also for cancer prevention. Because if we can make ourselves not generate mutations, we can prevent cancer from happening.

• 11:09Flora Lichtman?

  Manny, the bats you study also seem to not get cancer, right? Is the mechanism the same?

• 11:16Speaker 01

  Uh, if you look at the leaderboard for the 20 species of the lowest cancer risk, about five of them are bats. So bats both have the ability to improve their like DNA repair. So when they acquire damage, they're better at dealing with it than like, say, a mouse's. But they also have a very elephant-like mechanism where they're also able to purge damaged cells. So it's basically having like both the ability to maintain a better genome and also a better sorting facility for getting rid of the junk.

• 11:54Flora Lichtman?

  We have to take a quick break, but don't go away because when we come back, can animal superagers teach us how to live longer, healthier lives?

• 12:03Speaker 02

  If we learn from evolution how to live like a bat that can fly until its last day, I mean, that that would be amazing if people could enjoy their lives productively until the very last day.

• 12:21Speaker 03

  Support for Science Friday comes from the Heising Simons Foundation. Unlocking knowledge, opportunity, and possibilities. More at hsfoundation.org.

• 12:35Flora Lichtman?

  You know, Vera, I think everyone listening to this is wondering, can we learn from these animals to help ourselves live not just longer lives, but healthier lives?

• 12:46Speaker 02

  Oh, yes, we could learn so much. And if we talk about genome maintenance and more accurate DNA repair, that seems to be conserved across many long-lived mammals, long-lived animals. But the mechanisms are different, which is amazing. So we looked at anti-cancer mechanisms in naked morat. We find something entirely different. They evolved unique adaptations linked to subterranean lifestyle. They started making a lot of hyaluronic acid to squeeze through tunnels. And that now prevents cancer in them.

• 13:24Flora Lichtman?

  Oh, wow. And also, people know that from skincare, right?

• 13:26Speaker 02

  Yes, it is in skincare. It's in many cosmetics. But in the naked morat, they have it inside their skin in very large quantities. So their evolution took this path. And we humans, we're also pretty good at DNA repair, but we didn't have the same evolutionary pressures. So we are missing some of these adaptations. And we can develop some strategies to bring these adaptations into human biology. And then we would definitely benefit because it's something that we are missing, but we can improve upon.

• 14:00Flora Lichtman?

  How do you, what do you expect the treatment to look like? Is it gene therapy? Is it a pill of whale protein?

• 14:07Speaker 02

  Well, there may be different strategies depending on every adaptation. So let's say with naked morat, we are a little bit further along because we were thinking, okay, how can we increase the level of hyaluronic acid? Of course, you can apply it with a cream, but it won't get through your skin. It's just a good moisturizer. But if we develop small molecules to slow down breakdown of degradation of hyaluron inside our skin. Then we can increase our own levels of hyaluronic acid. And that was, we published a paper because we gave this small molecule to mice with cancer and they became a little bit more like naked morats.

• 14:52Speaker 02

  Their tumors didn't spread it just with applying this small molecule that could be orally administered.

• 14:59Speaker 01

  We also, because of basic science research, just have a lot of data and also pharmacological research, a lot of these big databases of how different drugs change your gene regulatory networks. So another way of translating this research is just looking at those two things with machine learning and taking advantage of the new AI tools now out to basically look for drugs that are already FDA approved that happen to have these like beneficial like, oh, it makes this look more like the naked morat or it makes this look more like the bowhead whale, right?

• 15:30Flora Lichtman?

  Is any of this moving out of the lab and into, you know, clinical trials?

• 15:36Speaker 02

  We analyzed DNA repair across 25 species of rodents. And we found the innate pair was more efficient in long-lived rodents due to another protein, not CRBP, but protein called sir two and six. It's also a genome maintenance protein. And we searched for activators and we found a natural compound from brown seaweed called fucoidin. So it's very healthy. People in Japan, South Korea eat brown seaweed as part of soups and stews. So it's very safe. And we took fucoidin, we found it activates sir six very strongly.

• 16:21Speaker 02

  Then we gave fucoidin to old mice and mice started to live longer and their genome stability improved. So right now we already started a clinical trial and we see if now the strategy that we learned from rodent studies can actually be safely applied to extend human health.

• 16:40Flora Lichtman?

  Fucoid, you heard it here first. Manny, what's your hope for this research?

• 16:46Speaker 01

  You know, if you ask an audience of people who here has had someone die of cancer, who here has had, knows someone who has like died of heart disease, right? So like, you don't usually get hands that are lowered. And these are things that have a huge like societal impact, right? Like, we spent so much money just trying to like play this game of whack-a-mole to deal with, like, all the different ways cancer can pop up and all the different ways heart disease can pop up. The thing that's like really interesting about studying long-lived animals is that they live long. And so as a result, they have a lot of preventative mechanisms as well. So we're not just talking about like using like naked mole rats and elephants and whales and bats to discover cures for cancer and aging and like heart disease.

• 17:31Speaker 01

  We're actually also talking about looking for preventives for all these things. So that way, people will eventually like be in a generation that barely knows what cancer is, right? Or, you know, like any other kind of like aging-related illness.

• 17:45Flora Lichtman?

  Vera, your hopes for this research?

• 17:48Speaker 02

  Yes, I'm also looking into the future where there will be less human suffering because these diseases, cancer, heart disease, diabetes, they cause so much human suffering. And if we learn from evolution how to live like a bat that can fly until its last day. I mean, that that would be amazing if people could enjoy their lives productively until the very last day. So this is my hope.

• 18:14Flora Lichtman?

  Dr. Vera Gorbenova is a professor at the University of Rochester and co-director of the Rochester Aging Research Center. And Dr. Juan Manuel Vasquez is a biologist and assistant professor at Pennsylvania State University. Thank you both for joining me today.

• 18:29Speaker 02

  Thank you. Thank you.

• 18:36Flora Lichtman?

  Today's episode was produced by Rasha Aridi. I'm Flora Lichtman. Thanks for listening.