Biological Mechanisms and Future Human Applications

You're listening to Shortwave from NPR O est G bekay. This is Ross Anderson, a staff rider at the Atlantic And as you heard, he has a dog. rest He's deled to be on the show. Now he thinks so. Like I've called him over to play Fetch. Ross called Forrest over because he was the inspiration for Ross's reporting on a company called Loyal They're working on a new drug to fight against every dog lover's greatest fear, inevitably losing their pet to time. The hope is this new pill will extend the lives of dogs And the vision all started in the rural outskirts of Austin, Texas where Loyal's founder Celinee Holloa grew up Her whole childhood, she was surrounded by animals forming deep loving bonds with a lot of them. She told me her family had Fteen dogs and cats and most of them were strays. and she fell in love actually with A horse that lived locally. He lived with a ratchet cowboy is how she described it to me bond with animals was on her mind as she went off to college. She worked at a neuro oncology lab and so I got to kind of see just the horror, the cosmic horror, really, of brain cancer very close up, and it had a profound effect upon her. Loyal's drug is still working through the FDA's approval process preliminary results show it could extend your dog's life a year or even two. and just as importantly, their health. No one wants to pack on another two years of those like kind of heartbreaking final months of a dog's life when they're struggling with the very worst health issues. This is intended to not only extend their lives, but also like make kind of the back half of their life much more pleasant for them, kind of in a whole body way And as exciting as this pill is on its own for dog lovers, it also serves a much bigger purpose To be an important pit stop on the quest to eventually lengthen human lives We have certain things in common in our body plan, but also they age in many the same ways that we do. They get the same cancers and are treated with the same chemotherapies. So today on the show, why a boon for man's best friend may be a boon for humanity itself down the line We get into how this pill works for dogs and why that same mechanism may be a blueprint for a pill for you one day Plus, why scientists haven't gotten the job done for cats yet I'm Regina Barber and you're listening to Shortway The science podcast from NPR Okay, Ross, you're here to tell us about a new pill that may make our dogs live longer and healthier, but this isn't the first time that science has successfully made organisms live longer. What are some other times or ways scientists have extended life? Yeah, well, I'm sorry to report that it starts with worms starting in the nineteen nineties, a brilliant scientist named Cynthia Kenyan lengthen doubled the lifespan actually of sea elegans, the round worm. I love sea elegans. All of my biology friends work on those. Yeah, ye, they're kind of like the classic sort of easy to mess with in the lab. And in this case, it really benefited them because they they got their lifespan doubled. Doubled. Wow. What is their normal lifespan? Yeah, sea elegans, you know, it's not a long lived animal, right? It only lives about two to three weeks. And so by doubling it, I think, you know, she got it up to a month, which is something Right. So Ross, I'm interested in knowing like in this specific case with Loyals's pill for dogs How does it work biologically? Yeah, well, it actually goes at the metabolism, which may be counterintuitive, but there was a striking study done in the nineteen nineties by Pureinna, the dog food company, where they took fifty Labrador puppies. and they split them up and they fed half of them twenty five percent less, sorry to those dogs. But in the end, they ended up living like a full fifteen percent longer, just like wow really, really dramatic result. And so that was a big clue that life extension in general might be attacked through the metabolism and that particularly you could do it through dogs. Now when you put that together with the fact that technique that had extended the lives of roundworms actually attacked the insulin receptors of those roundworms. So that also was a metabolic pathway. Similarly, there is accumulating evidence that GLP one s could act in a kind of life extending way across the whole body And those also are metabolic drugs And so yah, I think there's just it's not just Seline and looyal. I think in the life extension industry in general, metabolism is hot right now. There's just a real sense that this could be the key to, you know significantly extending notot just dog's lives, but potentially our lives. This is surprising. like when I think about aging and dying, I usually think about heart failure or something happening brain or something, how exactly does the pill target metabolism? And how does that help with aging? Okay, so the first thing to know is that as dogs age, their insulin sensitivity gets a lot worse So like in a healthy young dog As soon as you know they wolf down some kibble, their blood sugar goes up and their body releases just like a tiny bit of insulin. And all the tissue around their body that absorbs glucose, you know, senses that insulin, that like tiny, tiny pulse of it and gobbles up the glucose, right As they get older, those tissue systems around the body, they get bad at listening for that insulin. And so as a result the dog has to pump more and more insulin throughout its body in order to get to have that glucose get absorbed. And that excess insulin causes inflammation all across the body and aggravates a lot of its aging. And so the loyal pill helps to restore that insulin sensitivity. And the way it does it is once the dog has like the kibble and its blood sugar spikes, this pill dissolves, the particles kind of go all throughout the body like little Paul reveres telling those tissue systems, listen for the insulin, listen for the insulin. Wow. And that way The dog doesn't have this huge glut of insulin flowing all over its body, accelerating its aging processes, causing inflammation, et cetera, et cetera. Yeah. Where is this pill at? like so the FDA has to approve the drug, when can we expect to see it available for people to use for their dogs? Yeah. so there are three kind of main prongs of conditional approval at the FDA. and they are efficacy, which is like, does the thing work? manufacturing Can you make it in a reproducible way? And then safety. And right now, Loyal has had the efficacy and safety. They have conditional approval for both of those. So they're only waiting on manufacturing. And I don't manufacturing drugs is super complicated and I don't want to trivialize it. but of those three, that's like the right one to be outstanding. L I think that's a hurdle they're going to get over And so It's looking like the pill will be available early next year. Oh, wow, that's soon. Yeah. in the meantime, they're running a clinical trial that is going to take you another four or five years for final approval, but they can sell it with conditional approval starting probably next year So, you know, I have a personal question. This is being focused on dogs, but why not cats? I have four cats. and are there pills for cats? You know, I know that there are some cat longevity startups, so I have that good news to report to you. But I will say that one reason that I think dogs may have edged out cats is like the first kind of sample animal for this is They just it's easier to get them to take a pill . My cats won't take pills. I thought it was gonna be because cats live longer, but I think you're right. Yeah. So dogs are better at taking pills. Do the dogs, do they like it? Is it okay? Yeah, well, I'll tell you what, dogs are better at taking pills, but they're not perfect. And because this is going to be a daily pill that they will take for literally the rest of their lives, Loyell actually put together a focus group of like twenty taste tester dogs to get the flavor right. And it was interesting they couldn't just do it one day because Dogs will just like chomp down anything the first time, right? Right. So they had to do multiple days and some of the dogs were actually like ning In fact, one of them spat out one of the flavors they didn't like and ended up peeing on it. Oh my gosh. what are the flavors?? I think it's a beef flavor. It's what they ended up settling on. If it was cats, it would be seafood.. Okay, so this is maybe the most important question for you. I know you have a dog at home. His name is Forrest, right? I do. Forrest is he's actually sleeping at my feet right now. So if this pill gets approved. Are you planning to give it to your dog? Yeah, so Frest is four years old. So he's in a little bit of a sweet spot because the clinical trial to see like if and how well this thing works to like very high precision will be done by the time he's eligible. Dogs are eligible at ten years old. Wow, you're ready Yeah. And if they pass with fine colors, I'll absolutely give it to them. Oh my gosh. I want them around logger. So. there he is Ross, thank you so much for talking with us. I had a great time. Yeah, Regina. this was great. Thanks for having me on If you like this episode, why don't you share it with a friend that you know is obsessed with their dog? They're going to love it and they're going to thank you for it This episode was produced by Urunda The Neyer. It was edited by our showunnerer Rebecca Ramirez and Tyla Jones Check the Facts. Quacey Lee was the audio engineer. I'm Regina Barber. Thank you for listening to Shorewave from NPR how they verified the age of the dogs. I just thought it was funny that like some of the dogs needed Facebook photos. What? Yeah, because People don't have like their dog birth certificates. so they had to like put like screenshots of their Facebook posts showing that, you know, them being like, I got a new puppy, you know it's timeestamp. that worked for age verification