The Science Pawdcast

Episode 14 Season 7: Chilly Dips, Flatfaced Pets, and Extending Dog Lifespan with Celine Halioua

• Jason and Kris Zackowski • Season 7 • Episode 14

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We explore the cutting-edge science of extending dog lifespan through innovative drug development with Loyal founder and CEO Celine Halioua, who shares the company's groundbreaking approach to canine longevity and health.

In Science News:
• Cold water immersion after exercise shows no benefits for women despite its popularity among fitness influencers

In Pet Science:


• Brachycephalic dog and cat breeds now resemble each other more than their wild ancestors due to selective breeding

Our Guest Speaks about:

• Loyal's first drug mimics the longevity benefits of caloric restriction without reducing appetite
• Large dog breeds age faster due to persistently high growth hormone levels that weren't naturally selected for
• Loyal is conducting the largest animal health study ever with 1,300 dogs to test longevity interventions
• The company hopes to bring their first longevity drug to market within a year
• The goal is to add at least one healthier year to dogs' lives while improving quality of life during aging
• Aging dogs develop many of the same diseases as aging humans, making them excellent models for longevity research

Loyal: https://loyal.com/

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Speaker 1:

Hello science enthusiasts. I'm Jason Zukoski. And I'm Chris Zukoski, we're the pet parents of Bunsen, beaker, bernoulli and Ginger.

Speaker 2:

The science animals on social media.

Speaker 1:

If you love science.

Speaker 2:

And you love pets.

Speaker 1:

You've come to the right spot, so put on your safety glasses and hold on to your tail.

Speaker 1:

This is the Science Podcast. Hello everybody and welcome to the Science Podcast. We hope you're happy and healthy out there. This is episode 14 of season seven. As I mentioned in last week's show, Chris and I are in the busiest time for us as teachers the next. Well, we've been through a busy week, we've got another one or two, we got the podcast out. It's a really good show. So I think we'll just get right to it and cut down on the small talk.

Speaker 1:

In science news we're going to be looking at that cold water dipping fad. Is there any science behind it? Maybe, maybe not. And in pet science we're looking at how the brachycephalic dogs and the brachycephalic cats are starting to become more closely resembling each other than their wild counterparts. Our guest is so interesting and so on point with what we care about as a family science dogs, but also potentially extending their lifespan. And our guest is Celine Heliwa, who is the founder and CEO of Loyal, and she's going to be talking to us about Loyal's drugs that are in trial right now for uh, to increase the longevity of dogs. So fascinating. All right, let's get to it. There's no time like science time this weekend Science news. Chris, do you want to take a cold dip in an icy lake ever.

Speaker 2:

Never.

Speaker 1:

How about tomorrow?

Speaker 2:

Maybe someday.

Speaker 1:

You're not a fan of swimming in cold waters.

Speaker 2:

Absolutely not, Jason. You, on the other hand, enjoy it. But there was something interesting. When I went to Quebec and I don't know what happened to me, I went into cooler water and I don't know what happened to me. I went into cooler water and I stayed at a family's house Like I was. What's the word?

Speaker 1:

for it. You're billeted there almost.

Speaker 2:

Yeah, I was. It was almost billeted at this house with this wonderful family and they had a pool in the backyard. In Quebec Most people had a pool in the area that I was at. And she said, oh, every night we go for a dip in the pool. And I said what? And of course, because I was in Quebec, I thought let's try anything. And she said what she said if you move, it's good, but in French c'est tout beau move it's good, but in French it's si tu bous. And so then I came home and we went swimming in Waterton, which is south here in southern Alberta, and I went into the cold kind of river thing and you were like who's this woman that came back from Quebec? You were shocked that I was in the cold water.

Speaker 1:

You were fueled by wine and cheese. You had superpowers from going to Quebec for a little while.

Speaker 2:

Yeah, definitely fueled by the food there was delicious and probably nutritious, but it was very good.

Speaker 1:

And from my part, growing up where I have grown up in Alberta, the water here like there is no warm water in Alberta, canada. The lakes maybe warm up a bit by I don't know end of July, start of August and we would go swimming in mountain lakes. I love it. I love swimming in mountain lakes. You can't stay in there for hours at a time, but there's nothing like it. Anyways, that's where the study comes in. There has been a lot of I want to say health and fitness influencers or people wanting folks to get in on the cold water plunge for health. Have you heard about this, chris? Has this been on your radar? It's been on mine.

Speaker 2:

It's been on a little bit of my radar for sure where there's potential health benefits for dunking in cold water after you work out, or having a soak in hot water or warm water helps you relax. So there has been lots of studies done on men, but unfortunately studies on women are few and far between.

Speaker 1:

So that's where this study comes in. They took 30 healthy women with an average age of 23.3 years. There was an exercise protocol. They had to do five sets of 20 drop jumps from a 0.6 meter high box.

Speaker 2:

Now, Jason, do you do drop jumps during your workouts? Your workouts sound very high intensity training.

Speaker 1:

Yeah, my Monday workouts. I do conditioning to keep my old body that's getting decrepit as in good a shape as I was when I was younger. I do some jumping around, I flip tires, I push this super heavy sled thing. There's like rope slams that I do. It's like all of these different exercises. Yes, I do drop jumps.

Speaker 2:

So jumping off of a box that is just over half a meter in height, jumping off of the box onto the ground and then explosively jumping back onto the box, 20 times Five sets of those, you've done that.

Speaker 1:

Yeah, I'm not a great jumper, but yeah, I have done that.

Speaker 2:

Yes, oh, I can tell you right now. If my trainer said let's do these, I would say no, thank you.

Speaker 1:

Yeah, that's a drop jump. So five sets of them. Anyways, they had to get the people to exercise because the claim of cold water is it does a bunch of good things for your body. After this exercise, one group was put into cold water. The cold water was 10 degrees Celsius for 10 minutes. That's chilly 10 degrees Celsius. You're going to feel that when you get in there. The other group was put in hot water, so that's 40 degrees Celsius for 10 minutes. And then there was a control group who'd got nothing. Maybe they were just given a magazine. They had to wander around. Anyways, those were the three different interventions.

Speaker 2:

And not only that there were the interventions, but there was, it happened right immediately after the exercise, those scary sounding jumps, and then again two hours later. So yeah, back into the cold drink you go.

Speaker 1:

They took some measurements, obviously measurements before, measurements after. They looked at for muscle strength, so that was a maximal voluntary contraction, so squeezing as hard as you can, how sore you were. Of course that's subjective Muscle swelling. So doing all those jumps maybe your knee might be swelled a bit. And of course that's a claim of cold water soaking, as it helps with swelling, and a biochemical marker which looked at serum creatine kinase levels. So creatine of course is in a lot of red meats. You can take that to. I guess there's some. There's. There is evidence that if you take creatine it does help with weightlifting. So this is something to look and see if you make more natural creatine from the cold water soak.

Speaker 2:

And they did these assessments, a baseline assessment before all that jumping and at 24, 48, and 72 hours post-exercises.

Speaker 1:

Not the biggest study group size, but the findings I think are interesting in that there was no difference in muscle strength, soreness, swelling or that creatine among the three different groups soaking in hot water, soaking in cold water or doing absolutely nothing. In fact both cold and hot water did not accelerate recovery at all. There was no difference between that and the group that was the control group.

Speaker 2:

This study highlights the need for more gender-specific research exploring how does exercise affect women. But there are some psychological considerations from this study. Psychological benefits were not observed, but psychological factors, such as feeling refreshed or feeling less fatigued when you've gone for a soak, may influence a perceived recovery and motivation. So a bit of that placebo effect oh, I feel good, I feel relaxed. I'm sitting here in this hot water and I don't want to leave. Now the subjective benefits. Although they weren't measured directly in this study, they could play a role in athletic performance and whether or not athletes adhere to their training regimens.

Speaker 1:

I guess, as we wrap this up, there was a study that mimicked this in men. Same kind of idea there's 30 healthy men and they were looking at muscle damage and then cold water immersion and it showed improvements in the cold water soak versus the controlled group for men, with the colder water being more effective than the somewhat lukewarm water.

Speaker 2:

Their temperatures were different. Their cold water was 10 degrees for 10 minutes, and also cold water at 15 degrees for 10 minutes.

Speaker 1:

Yeah, now we should also say this is a 30-person study, so very small. I do think there needs to be way bigger studies on this, a lot more conclusive evidence than like 30 dudes who sat in some cold water before. That seems like much too small a sample size. Though, as you said, we can't discount the psychological benefits. If you think it's helping you, especially in like athletic performance, that your mindset is a huge part of you being able to do anything, so I get that, that it gives you a psychological benefit, all the power to you. It's not bad.

Speaker 1:

They didn't. The studies don't show that if you do this it is detrimental to your health, so at worst it's doing nothing and at best it could help.

Speaker 2:

There you go, and I always say mind over matter when I'm at the gym.

Speaker 1:

I think if you have to soak in 10 degrees Celsius, you're going to have to have a lot of mind over matter, because that matter is 10 degrees Celsius you're sitting in. I guess, that's science news for this week. This week in pet science we are going to be looking at brachycephalic breeds of dogs and cats. Chris, do you know some of the brachycephalic breeds of dogs?

Speaker 2:

The Pekingese. I used to want a Pika Pom and you said- oh yeah, I remember this, I remember. I'm like Jason. They have a Pekingese mixed with a Pomeranian and it's called a Pika Pom. Isn't that so cute? And you said no.

Speaker 1:

I'm a big dog person, Chris.

Speaker 2:

I know.

Speaker 1:

Golden Retrievers are bigger. I'm a big, Though. My sister Marina's family just got a new dog and it is freaking adorable. It's like a Corgi mix rescue thing. It is cute.

Speaker 2:

Yeah, she very much is cute. Her name is Rosie, but yeah super cute, but the Pekingese Pugs are the type of dog that are brachycephalic. The Brussels Griffin dog, the French the Boxer, the French and English bulldog are both brachycephalic dogs also cats are brachycephalic, the flat faced like the persian cats the persian cats for sure, and they all share a dramatically distorted skull and those cute flat round faces and their noses pushed up between their eyes and.

Speaker 2:

And those features actually are not occurring naturally but they are the result of selective breeding because humans really baby-like traits that we find in humans, that we find cute in humans and we're selectively breeding them to transfer into the dogs and cats we're selectively breeding them to transfer into the dogs and cats.

Speaker 1:

So one of the selective breeding traits that we've put into dogs is how dogs can move their eyebrows relative to their wolf ancestors. Have you ever watched Bernoulli move his eyebrows?

Speaker 2:

It's so cute.

Speaker 1:

He has very expressive eyebrows and I don't know if it means anything. He's just moving his eyebrows, but it looks like he's thinking and of course that was a trait that we've bred into dogs because it gives them a human-like expression. Right, that we move our eyebrows, like when we're surprised. Our eyebrows go up when we're perplexed. We might raise one over the other, and that's what Bernoulli does. I love. He goes one eyebrow than the other, one eyebrow than the other. Callan, oh, she would do that too.

Speaker 2:

Yes, and that's very distinctive, a very distinctive difference between Callan and Beaker. Beaker is very straight-faced, no expression, looking at you, whereas Callan, you could talk to her and she would raise her eyebrows, she would tilt her head, she would really engage with the conversation.

Speaker 1:

She was a good girl. Anyways, let's get back to the study. The study comes from proceedings in the National Academy of Science and one of the interesting things they looked at was how these cats and dogs are of different species, now resemble each other, like a cat and a dog now look more like each other than their own wild ancestors, effectively erasing millions of years of evolution. This is an example of convergent evolution, and I actually teach this in Science 20, convergent and divergent. But convergent evolution is where you have traits that evolve independently, like you might have. Example winged animals birds have wings, bats. Bats have wings, but they're not of the same species, so species independently get similar traits. This is due to usually natural selection. There's an advantage to fly, and if you are a bird you fly away, and if you are some kind of rodent thing, you get wings over time and you fly away like a bat yeah, like a bat.

Speaker 1:

So there's some kind of advantage and you both get it.

Speaker 2:

But in this case, chris, it's not natural selection it's artificial selection yeah because humans are selecting for those baby-like features so flat faces, high noses, round heads. But those skull shapes do not actually exist in nature and unfortunately there's some significant health consequences for the animals having those traits. Brachycephalic animals actually cannot survive in the wild because they have certain health issues like difficulty breathing, and they often require surgery to correct that. They have eye problems, dental issues, neurological conditions and they actually can't tolerate heat and exercise due to the poor oxygen exchange and of course, some of these brachycephalic breeds are way more susceptible to this than others.

Speaker 1:

So this study looked at over 1,800 animals 148 domestic cats, 677 domestic dogs and they included some extremely brachycephalic dog breeds which we've mentioned bulldogs French bulldogs, japanese chin and three extremely brachycephalic dog breeds which we've mentioned bulldogs French bulldogs, japanese chin and three extremely brachycephalic cat breeds the Persian Himalayan and the Burmese. Do you know how many times people say Burmese mountain dog?

Speaker 2:

Lots, yeah, but that's a cat breed so many times.

Speaker 1:

Anyways, the skull data was from dozens of wild canids, of the dog and the felids, the cat family. So they're looking at these domestic animals versus wild animal skulls. They scan them with CTs and use museum specimens and they modeled the skull by 3D printing them and then looked at their atomical landmarks. So this is a pretty in-depth study looking at skull shapes.

Speaker 2:

So the anatomical discoveries included. The brachycephalic animals have skulls that are more similar to each other than to their wild counterparts. Just like Jason said earlier, they actually have tilted palates and shortened nasal regions, which results in those restricted airways. And actually this was very interesting Some Persian cats actually lack nasal bones.

Speaker 1:

So I guess where we could wrap this up is that the evidence seems to suggest that dogs and cats use different genes to develop these brachycephalic traits, and understanding these genetics could also perhaps understand causes of those health problems and inform better breeding practices, meaning that, I guess, if your dog has that gene, perhaps that's not a gene you decide to pass on, especially for the really severe brachycephalic health problems for the really severe brachycephalic health problems.

Speaker 2:

Or what you could do is adopt a mixed breed animal from a shelter. That could be a suggestion, because those pets are less likely to suffer from inbred health problems.

Speaker 1:

Also, chris, there's been a big push because it's a taboo subject, right, because everybody loves their dogs and everybody loves their cats and for the longest time it was not something really you would talk about because it causes hurt feelings. I'm sure people listening to this have a few people have a pug or a French bulldog and vets are now saying perhaps now is the time to stop that extreme breeding and maybe have the breed standard go back to what it was 60, 70 years ago. Stop selecting those extreme traits. Start selecting the traits for longer nasal passages and a less flat face.

Speaker 2:

Absolutely, because sometimes those animals are disadvantaged, like they are walking around and they just poke their eye. They poke their cornea with something sticking out, because their eyes are just googly on the sides of their heads, like that.

Speaker 1:

Yeah, they are cute and they are good dogs and I don't know any Brachycephalic cats, but I've met a few pugs in my life and they're pretty cute little dogs. But I think we have to go with the science and the experts here. That's pet science for this week. Hello everybody, here's some ways you can keep the science podcast free. Number one in our show notes sign up to be a member of our Paw Pack Plus community. It's an amazing community of folks who love pets and folks who love science. We have tons of bonus Bunsen and Beaker content there and we have live streams every Sunday with our community. It's tons of fun. Also, think about checking out our merch store. We've got the Bunsen stuffy, the Beaker stuffy and now the ginger stuffy. That's right, Ginger the science cat has a little replica. It's right, Ginger the science cat has a little replica. It's adorable. It's so soft, with the giant fluffy tail, safety glasses and a lab coat. And number three if you're listening to the podcast on any place that writes podcasts, give us a great rating and tell your family and friends to listen too. Okay, on with the show.

Speaker 1:

Back to the interviews. It's time for Ask an Expert on the Science Podcast, and we are thrilled to have the founder and CEO of Loyal, Celine Halliwa, with us today. Celine, how are you doing today?

Speaker 3:

I'm doing great. You nailed the name.

Speaker 1:

Oh, I wrote it phonetically on my notes.

Speaker 3:

It's a hard one.

Speaker 1:

Yes, as we were talking, I'm a high school chemistry teacher and there's all manner of names I have to learn and usually I have to spell them.

Speaker 3:

Oh geez, I actually have six names and I tortured all of my teachers with it. It was horrifying.

Speaker 1:

Oh, I have one of my classes, olivia and Olivia, so keeping them, I just call them the Olivias, I just give up. But, celine, one of the questions we asked right off the start is where are you in the world? Where are you calling into the show from?

Speaker 3:

I am currently sitting in a hotel lobby in San Diego. My dog is staring at me because he's very bored that I've been sitting here for a while.

Speaker 1:

Whoa.

Speaker 3:

But otherwise it's beautiful. It's a sunny day out here in SoCal.

Speaker 1:

Nice. Now we're going to get to some of the exciting stuff around what you're working on now. But just for background, what's your training in science?

Speaker 3:

I did an undergraduate degree in neuroscience. I then started a PhD at Oxford in the economics of preventative medicine. I've also done a lot of studying in nanobiotechnology, and then I dropped out of my PhD pretty close to completion to go work at a venture firm that invested in spoiler alert longevity science and longevity therapeutics.

Speaker 1:

When you were young. Were you a science kid, or did you? Did the bug bite you later in life?

Speaker 3:

yes and no. So I did science fairs a lot and I'll always remember I got some gold star, blue ribbon, something like that, because after it's a little bit cringe thinking back on it but after hurricane katrina the levees broke in new orleans. Obviously I did a science fair project on what's the best type of material to manufacture levees out of, which was very unintentionally political, also did something around like a bridge collapse. But I actually in high school was an art kid and I got into college originally for art school and then made a. Yeah, no, I was not a kind of classically good student from a GPA standpoint, but I found my calling in neuroscience and just did a hard pivot and have never regretted it.

Speaker 1:

So I wonder if some of that creativity is why you are where you are.

Speaker 3:

I think so. I think so. I think I ended up in sciences because I fell in love with it, not because I felt like I needed to get a job of a certain stature Right, and yeah, I don't know. I think I've always been really good at finding. One of our values at Loyal is opportunities at the intersection right. One of our values at Loyal is opportunities at the intersection right. If you combine fields that aren't often considered to be within the same scope or plane, you actually find really interesting new opportunities to work on. I think Loyal is really the personification of that, with longevity, science, dog love and art right. It's a consumer brand in many ways.

Speaker 1:

Yeah, yeah, I get you. And before Loyal, you worked at a venture capitalist firm called the Longevity Fund.

Speaker 3:

So I definitely never thought I would be a founder or CEO. My parents are not entrepreneurs Actually, my mom's a teacher too and my dad works in carpentry, woodworking stuff and I got really interested in venture capital because, if you're not familiar with venture capital, it's basically a very early stage of funding, for think of it as like crazy ideas that are more likely to fail than succeed, but if they succeed could be really important, right? So venture capital is a really important high risk funding mechanism for a lot of really ambitious and interesting science, and I thought the way to have my impact on the world would be to help fund new science, translating from the laboratory into, hopefully, new medicines.

Speaker 2:

Right.

Speaker 3:

And that was how I got exposed to the ideas that led to Loyal.

Speaker 1:

So that's the crux of why we so wanted to talk to you. On our show is, I stumbled across a tweet and it was about a longevity treatment for dogs which is bananas, and I was wondering if we could talk a little bit about that like as much as you can, I know, because it's probably tush, but right about that. But I was wondering if you could talk maybe a little bit about why dogs and why the push for the extending the lifespan of dogs was the drive for this.

Speaker 3:

Yeah, so I. I never thought I would start a dog longevity company. I've always been a very big animal person. I've been vegetarian my entire life.

Speaker 3:

I grew up with 15 cats and all these rescue dogs and wild animals that we would rehabilitate and I have my dog here right now, but I was initially working on human aging and human longevity and kind of this idea of can we develop drugs that target the way we broadly age over time to reduce the risk of us developing cancer, nerve zone disorders, like other age-related diseases, in our later years? We think about these diseases as very binary right. One day you're healthy, the next day you're diagnosed with cancer. One day you're healthy, next day you're diagnosed with dementia. But actually, mechanistically, these diseases develop over decades.

Speaker 3:

Parkinson's, for example, which is one form of nerveative disorder, so a disease where you lose brain matter, and it's very debilitating for the patient and we're not able to treat. Currently there's some evidence suggesting that you start developing the precursors of the disease decades before in your 40s, in your 30s, potentially before you're actually symptomatic and therefore diagnosed with it, and so that always just seemed ridiculous to me that we were waiting until, basically, the damage from these aging diseases was so bad that you then start having marked loss of function, loss of quality of life, and then you try to develop a drug to treat it. Instead of can we develop a drug that reduces the risk of you ever getting diagnosed as cancer, with you ever getting diagnosed as Parkinson's disease, with you getting frail with age and, long story short, the biology has actually been there for a long time. The kind of foundational biology between behind all of our drugs is actually older than me and humans.

Speaker 3:

To prove that a drug is extending healthy lifespan is just logistically such a difficult feat. I actually have no idea how old you are, but I'm assuming you're middle-aged, and if I gave you a drug today and I was like, okay, let's see if it extends your lifespan, it would take decades for us to have any definitive data. And so the initial insight around dogs was dogs are very biologically similar to us. They've lived with us for tens of thousands of years, we've co-evolved with them. But they also live a much shorter life, and so you can see if a longevity drug is working in a period of time that is much more relevant and feasible, candidly, from a company perspective. And if something works in dogs, it might also work in people because of this unique relationship. Oh and, by the way, everybody wants their dog to live a longer, healthier life.

Speaker 3:

It's pretty yeah, it's like pretty consensus.

Speaker 1:

I would give 10 years of my life to my dogs in a second.

Speaker 3:

No, totally, and it's my dog's pretty, pretty old and so I can. Obviously I work in the field, but still, like every time I look at her, I think about it. Right, she's got like this pain that I don't know if it's going to come in three months or a year, but everyone knows the pain of losing a dog and so it's kind of was this like aha moment that built over a couple of years? I just got so convicted in the idea. I was just like I guess I gotta do this now.

Speaker 1:

and that was five years ago and dogs, like from our, from the research I've done on the show. They have a lot of similar age-related diseases as humans not a one-to-one, but similar pretty similar.

Speaker 3:

yeah, they basically get and die from all of the same age-related diseases approximately the same time in their lifespan, with the one exception being cardiovascular disease. Dogs don't get cholesterol, plaque buildups and associated heart attacks at as high a rate as humans do, but they get neurodegenerative diseases like we do. They get cancer like we do. They get frailty like we do. They get dementia. Yeah, they get arthritis Huge thing, and that's actually pretty rare. We do most research. Most pharmaceutical research and development and studying is done in mice and rats, and those animals just don't. They don't get age-related diseases like we do. So even trying to model dementia in a mouse is just much more difficult versus trying to model it in a dog, where my dog has dementia right. There's a lot of dogs walking around with dementia right now.

Speaker 3:

And if something helps them. It's an interesting proof of concept that it might help a human.

Speaker 1:

That's fascinating. So this brings us to the thing that's been making a little bit of news in the science community the dog community is the longevity drug that your company has developed, the canine longevity drug, and, if I'm not mistaken, it's in efficacy trials right now. Is that correct?

Speaker 3:

Yes, yeah. So we got basically this preliminary efficacy approval so we'll be able to go to market with the data that we have in dogs today showing what we think is benefit that will lead to lifespan extension, with FDA thinks is also that, and in parallel we're running this behemoth study in pet dogs over a thousand dogs across the US uh study in pet dogs over a thousand dogs across the us. Wow, what a huge size.

Speaker 1:

That's amazing yeah, it's really cool for animals, right like I break down science every week and it's like the study size is like 50 dogs. Yeah, that's right. So it's not very no yeah, you totally get it.

Speaker 3:

Yeah, it's the largest animal health study that's ever been run, as far as we know, by a pretty significant margin. I think in the end, once we're upping enrollment to actually 1,300 dogs and if and when we achieve that, I believe we'll be 2x bigger than the next biggest study. And it's 66 vet clinics across the US, dogs of so many different shapes and sizes, of so many different shapes and sizes. And the reason we did that is because you really need to capture the inherent variability in a dog right. We need dogs whose owners run with them every day and dogs who sleep all day, like my dog and dogs that are. She is such a she's not even a couch potato, she's a bed potato. The couch is not fancy enough for her anymore, she wants the bed. But you want to catch that right, because all of these things impact how a dog age. So, yeah, it's this massive study and it's such a cool study to run.

Speaker 1:

Oh, that's so exciting, so exciting, so I'm going to press the rewind button a little bit. How does the drug work? What are you targeting? As much as you can tell us. Obviously, you can't tell us exactly what's in it right now, but what does it do?

Speaker 3:

Yeah, so we have two categories of drugs. The drug I was just talking about, the drug that's closest to market. It's taking the biology of bluer restriction and its lifespan extension and making it more accessible for the average person and the average dog owner. So the kind of only intervention that has been shown consistently to extend lifespan and everything from or actually they had a first intervention that's been shown to consistently extend lifespan and actually the first time it was ever shown in any species, is caloric restriction, this idea of reducing the amount of calories that the animal or human intakes without having nutritional deficiency. This isn't like ridiculous caloric restriction but it's just 20% less In dogs.

Speaker 3:

There was actually this really cool study that was ran in the 90s by the dog food company ironically Purina, showing that if you've calorically restricted Labradors, litter mate paired Labradors, that the calorically restricted dogs live two years longer than their litter mate, had a two-year delay of cancer incidence still got cancer but they happened two years later on average Right and they had a six-year delay in osteoarthritis incidents, that's it's huge, it's huge, it's absolutely huge.

Speaker 3:

And this is this very much emulates what you get rats, mice, etc. There's a lot of work in humans on intermittent fasting and all of that for lifespan extension too. But the kind of fundamental challenge with caloric restriction is nobody wants to calorically restrict their dog for probably obvious reasons, right Like my dog is-.

Speaker 3:

It's like Labrador retrievers, I was going to say it would be like cruel, unusual to do that, as a Labrador owners to calorically restrict their animals, and so we wanted to develop a drug that emulates the what's happening inside the body, what's happening mechanistically when you calorically restrict a dog. That's causing them to have a longer life without suppressing their appetite and without simply just being a weight loss.

Speaker 1:

Like an Ozempic for dogs. You don't want it.

Speaker 3:

Yeah, you don't want an Ozempic for dogs. One Ozempic can make you pretty nauseous. People don't want their dogs puking everywhere. We don't know if it would make the dogs puke, but you don't want to take that risk. But also, more importantly, there actually was a weight loss drug in dogs that was approved a while ago. That worked by appetite suppression and it was a total market failure because people felt like their dogs didn't love them anymore Because you had so much joy out of feeding dogs and doing training with them.

Speaker 1:

For treats right.

Speaker 3:

Exactly, and if we're kind of honest with ourselves, a lot of our dogs being cute, it's our dogs begging us for food.

Speaker 1:

You're not wrong.

Speaker 3:

It's a hard truth.

Speaker 3:

It's a hard truth and so we really want to develop a drug that would emulate the benefits of restriction, but not just because it's telling your dog not to eat food.

Speaker 3:

And, long story short, we found that drug. That drug is what got the preliminary efficacy approval earlier this year. And, of course, the other really thing that's super important is safety. Right, we picked a drug that we don't have the safety approval yet, but from all the data we have, we believe we're going to be able to say pretty strongly this won't do harm to the average dog and we'll hopefully have a lot of benefit, right? So then it becomes a no brainer. It's not going to hurt your dog and and it helps them, or hopefully it helps them based off all the data and you can afford it, which it's not going to be. It's not going to be free, but it's not going to be like super expensive either. It's going to be within the range of other veterinary pharmaceuticals. Then it's a no-brainer for you to do for your dog. That's our lead drug drug and I'm happy to go into the other.

Speaker 1:

What's the name of it? Does it have a name yet, or are you guys still?

Speaker 3:

So it does have a name. I'm actually not allowed to tell you.

Speaker 1:

Oh okay, We'll just call it like anti-snackola or something like that.

Speaker 3:

Oh my God, that's great. No, so the kind of code name is LOITU, yeah, but it actually will have a super fancy pharmaceutical name. But we're not allowed to use it until the drug's approved, because otherwise you can think it seemed like a drug is approved. Oh my God, wolf Govee. Oh God, wolf Govee, that's actually good.

Speaker 1:

I like that. I do run a huge social media account for for dogs and we're 90% puns. So there you go.

Speaker 3:

Well, there you go, the puns are. I have a lot of fun as CEO making dog puns. It's one of the few joys and everyone has to laugh. They're on my payroll.

Speaker 1:

Oh, I see. Okay, so this loyal to. I'm sorry I forget, forget the actual name, because in my brain I was being a sarcastic boy too. I'm so sorry, selene wolf goby personally yeah trademark. So this is the one that's in trials. Do you have any data from that you can share with us? What, or is that a nudge? What can the average dog owner expect if things go the way they should and it's approved with their dog? If you get where I'm going with this, I totally get where you're going.

Speaker 3:

I would love to share data with you, even I don't know. I actually can't see the data at all until it's over okay and the study's not done for another four years oh my goodness okay so I will look forward to sharing that once I have my hands on it. Gotcha, there's a lot of like data, cleanliness, ethics, stuff to basically separate church and state yeah, I, I understand, I understand you.

Speaker 1:

You don't want to be what is it? Have the CEO, have their hand on the deal.

Speaker 3:

Yeah, no, I am very separated from it.

Speaker 1:

Gotcha, yeah, so is that the best case scenario? Is that the length of time for the drug to market? Or if it passes like health stuff, you'd get it out sooner because you have good evidence that it will be good for dogs?

Speaker 3:

If my line of yeah, that makes total sense. So we're hoping to bring this product to market in the next year. So the lifespan extension study isn't crucial for the kind of the initial preliminary approval. It's crucial to stay on market. So basically, we'll go to market with the data that shows that this drug is likely to be effective, kind of that preliminary efficacy approval I was talking about, and we've already gotten that approval, so that's gravy. And then in parallel we'll run this super intense in-depth study to formally quantify okay, it's one year of lifespan, it's nine months of lifespan, it's 1.8 years of lifespan, whatever it is, and that'll be required to stay on the market past about 2030.

Speaker 1:

Gotcha and best case it's mimicking the Labrador study right. Similar kind of stuff.

Speaker 3:

I think so. The line weaker in the sand is approximately one healthier year of life. I think the lifespan extension is super important, but actually we are using lifespan extension as a proxy for quality of life improvement.

Speaker 1:

Quality of life is as important, or more so with a dog.

Speaker 3:

That's what people really care about, because there is such a long decline, especially with larger breed dogs, where you have your dog and they're alive, but they're happy mentally but physically it's just they can't do what they want to do anymore and that's actually really hard to objectively quantify right. You can kind of look at a dog and tell are they younger, are they older, are they moving around in a better manner or in a more frail manner, but actually objectively quantifying that and normalizing it from optimistic dog owner to pessimistic dog owner is super hard.

Speaker 1:

Yeah, I understand. We have three dogs, two burners and a golden Bunsen is our oldest burner and he'll be turning eight right away and he has a slipped disc, so it's really hard. The last three months he's improved immensely. But, yeah, like he wants to do, but he couldn't do, so I get that.

Speaker 3:

Yeah, that's tough yeah, oh yeah, that's hard with the burners. They're such sweeties. But there are sweethearts you bet yeah, but it's like the bigger dog breeds have such shorter lifespans yeah, they do yeah yeah, so that's what our other drug is targeting it can we talk about that, do you mind?

Speaker 1:

Yes, absolutely. This is a terrible segue, but we have to save Bunsen and Berner. Yes, yeah, what's going on with your the other drug, could you talk to us about?

Speaker 3:

it. Yeah, so actually the first drug was already working on and I would say, my, my, my child, so to speak, as in this is the original science by which the company was founded. Is this idea that we all accept that if you love Bernie's Mountain Dogs or you love Great Danes or even Rotties like me, that you just have to accept that these dogs live much shorter lifespans, right? They can, at the extreme, live. Great Dane will sometimes live like six, seven, eight years. Six, seven, eight years versus if you'd be fortunate enough to be a chihuahua person or a mini poodle person, you're potentially getting 17 years with your dog and we all think this is natural, but it's actually really weird if you kind of step back and think about it.

Speaker 3:

Yeah, stupid I hate it is stupid. I definitely hate it too. Sorry about that, selena, I just get frustrated no, I literally agree, I'm, you know, I love all dogs, but I am a big dog person, I will admit it.

Speaker 3:

I we had an off-site with the team because we're a fully remote company and everybody flew in and we said bring your dogs, but of course, only people who bring their dogs or people who had small dogs so they could fly with them yeah and it was so funny because the team was like selene, you have so much big dog energy, you're scaring our small dog because you can't pet a chihuahua like you pet a roddy, like my roddy, I like smack her butt and like toggle with her.

Speaker 1:

My gushy faces you squish yeah, yeah, exactly.

Speaker 3:

You don't do that with a chihuahua. The chihuahua was like what the hell runs away. So it was. Yeah, I was like, oh god, I gotta get better at this, gotta get some more small dog energy in me. But any, if you look at mammals, like on average, actually, usually the larger an animal is, the longer their lifespan is. So then the mouse will live two years, while even rats live longer than mice, elephants live into the decades, whales live into the decades and there's no species where you see a 2x difference in average lifespan. So I'm pretty short. I'm not living twice as long as somebody who's six foot or six foot five.

Speaker 3:

Long story short, the kind of aha moment for Loyal is that when we selectively bred to create these dog breeds since all dog breeds are artificial, right, they are creations of humans and we did this by inbreeding in most cases, not because people are bad or whatever, just because they didn't know like they were inbreeding themselves. This was hundreds of years ago. They're inbreeding themselves and they're inbreeding their cattle and they're inbreeding their dogs and this was super effective to turn the domesticated wolf mutt dog into the poodle and the German shepherd and the Bernese mountain dog and the huge phenotypic diversity we see in dogs today, but unfortunately it also caused a lot of genetic issues. Great Danes get or sorry, sorry german shepherds get hip dysplasia. Bully breeds really struggle with the breathing if they have the flat faces. Goldens gets yeah exactly, goldens get a certain form of cancer at a much higher rate clean cancer.

Speaker 3:

You're right, yeah yep, and it's super terrible because you just you don't know it's there until they basically die of it that's what happened to our golden before Bunsen.

Speaker 1:

God, I'm sorry. No, it's golden. The owners know about it. Yeah, you bet.

Speaker 3:

Yeah, it's horrible. And anyhow, the initial thesis of the company was hey, what if the short lifespan of big dogs isn't normal, isn't natural, isn't inherent? But it's actually a genetically associated accelerated aging disease that we accidentally gave dogs when we were selectively breeding them for size, right, because if you pick the puppy that grows really big in puberty and you're like, oh, that puppy, okay, breed it to the other big puppy, you're not following that dog to be like, oh, what happened to the puppy that grew really fast in puberty, to see how they were at age seven? And it turns out that basically genetic pathways that cause a dog to grow and double in size really quickly in puberty also control rate of aging. And these pathways exist in us. They exist in all mammals, but in not dogs.

Speaker 3:

These genes, these kind of growth hormones, turn down quite a bit once the animal's fully grown. In dogs, in big dogs they don't. So in big dogs you're having these growth hormones that are circulating in the blood and they're telling the dog grow, divide, grow, divide. And that means the dog's getting really big in puberty. But then once a dog is fully grown from a skeletal perspective, those growth hormones are still circulating around and they're telling the dog's body now okay, still got to divide, still got to divide, and these dogs are literally turning over from a metabolic perspective, at the extreme of 2x faster rate.

Speaker 3:

So, long story short, you're just seeing that these big dogs are just, they have a compressed lifespan, they're aging at a faster rate, and so the thesis of the drug, which has also gotten this kind of preliminary efficacy approval from the FDA, is, once a dog is fully grown, can we turn down these levels of growth hormone that are such a high concentration in big dogs to levels that are seen naturally in dogs, but maybe a more like an Aussie shepherd, right, a dog that has a 14 year average lifespan instead of a seven year, and you're actually able to do that pretty safely because it's a level that's seen naturally in dogs anyhow. So, yeah, we have two programs we're working on that. One is an injectable, one's a pill, and that's my pet project personally.

Speaker 1:

Oh, my God, that is so exciting. Sign us up for when it comes out, because we've got two burners. Our baby Bernoulli. He just turned one a few days ago. He's bigger than Bunsen now, so he's our-. Wow, yeah, he's bigger than bunsen now, so he's our. Wow, yeah, he's our big baby. Yeah, I hope he lives as long as he can live. All dogs should. Yeah, yeah, very exciting. So that maybe just to wrap up about this drug slain, what's the end date for this one? The the lower the growth. I don't have a snappy pun for this big dog.

Speaker 3:

Short lifespan no good pun. Yeah, I'm sure we can think something through. Probably 2027 is what we're aiming towards. Yeah, this one's a little bit further out, but we're I'm very motivated personally too, so we are running as fast as we can.

Speaker 1:

Yeah, good science should not be rushed, yeah rushed.

Speaker 3:

Yeah, you know there's a lot of safety work you need to do. There's a lot of just understanding, right, because this is something that once the dogs are prescribed that they'll be on it for the rest of their lives. So it's certainly a really high responsibility to develop a medicine like this so both of these drugs?

Speaker 1:

when would your dog take them? Is it like as soon as they can when they've hit their maturity? That's what's. Do you know the answer to that? Yet I don't know.

Speaker 3:

Yeah, so we. It depends on the profile of the drug, so the one that will be approved first will be for senior dogs of most sizes, so 10 years and up. That's because it's targeting a pathway that we think can obviously delay rate of aging potentially, but also have a little bit of an acute beneficial effect and so starting it later can have a lot of benefit. Uh, for the big dog short lifespan it starts a lot sooner, in part because a lot of big dogs aren't alive at 10, but also because it's more of a preventative mechanism, right, it's more of a delay the rate of that dog's aging. So you need to start it a bit sooner. None of them are gonna be puppies, or for very young dogs gotcha.

Speaker 1:

Yeah, that makes sense. For the big dogs, yeah, oh, how about poor muzzle for the?

Speaker 3:

oh god, that's horrifying how about?

Speaker 1:

what about pupper? Paws no.

Speaker 3:

You should put it to your high school class. I feel like they could nail this. The TikTok generation got this.

Speaker 1:

I got size mutters.

Speaker 3:

Oh my God, it's actually really funny, that's all I got.

Speaker 1:

That's all I got I think that's pretty good. As we get to the end of our chat. Celine, one of the things we ask all our guests is for a pet story, and it can be a pet story, a current pet, a pet from your past pet, but we love when our guests share pet stories, so I was wondering if you have one for us.

Speaker 3:

Story. Oh man, I have a cat story.

Speaker 1:

Yeah.

Speaker 3:

Is that kosher?

Speaker 1:

Oh, cats are great yeah.

Speaker 3:

Okay, so I for the longest time only had a dog in my adult life. I had a lot of cats growing up and my boyfriend was very anti-getting a cat. I was like, come on, we need a cat. And he's like, absolutely not. I was like, fine, whatever.

Speaker 3:

So I fly to Texas. My family lives in Austin, I'm there for some work thing and if you're an Austin person, there's this very good burger chain, local burger chain called P Terry's that has like an absolute bang in veggie burger. So my dad picks me up from the airport it's super late, thank God, as you'll see and I'm like Dad, I gotta get some food. And so he picks me up and we drive to the P Terry's chain right by the airport. As we're driving through the drive-thru I see this little dash across and I'm like, oh my God.

Speaker 3:

And long story short, there was the world's tiniest kitten, like the size of my not large hands, that was living under a shipping container in the parking lot of this P terriers, of this burger chain. And this became a multi-day ordeal of trying to lure the kitten out of the shipping container. It was super wild. We tried burgers, I bought it a burger patty, I got it water, he would come out, he would eat. He was clearly starving. Long story short, my dad, I sent him on a mission. I'm like dad, you got to go find a cat trap and he calls everyone. He knows he procures a cat trap in less than 12 hours, which was amazing.

Speaker 3:

And we go back the next day and we get the stinkiest, biggest tin of sardines. We put the cat trap down and the cat jumps into it and the catcher and it turns out like literally like a one, one pound cat, so tiny. But then the next issue comes, which is I'm flying home the next day to california. So then the entire day we have this cat still in this cat trap, who's like hissing like crazy and I'm eating their sardines and then hissing and I'm like carrying this cat trap with this cat like and overall the pet codes and pet smarts and like trying to find somebody, like on a sunday, who you need a health certificate to fly with a cat, and I'm trying to find somebody to like give me this health certificate and I'm like, I'm like begging people. I'm like, please, I can't leave this cat, like I can't drop this cat off at a shelter. I need you to give me the goddamn health.

Speaker 3:

And, long story short, this like woman at petco is so sweet. She sees me like begging the like front desk person at the like at the vet clinic in there who clearly thinks I'm absolutely mentally insane, and she follows me out when I walk out, defeated. She's I know the perfect place and she calls her vet clinic and is like this woman needs help and they open the red carpet for me, they get me in the same day, within the hour, and get the cat all of the shots that she needed so I could fly with her like 12 hours later. And I ended up naming her after the burger chain, after P Terry.

Speaker 1:

P Terry.

Speaker 3:

Yeah, P Terry. So I now have a chaotic teenage kitten named P Terry, who I found in Austin.

Speaker 1:

That is a sweet story.

Speaker 3:

I love her more than anything. She's so cute. She every morning runs up to me and jumps in my arm and suckles on my hair. I'm guessing she was separated from her mom pretty early, which is so sad, but she's the cutest, cutest cat ever and I'm so glad I found her in that parking lot that's a cute story.

Speaker 1:

Do you, in hindsight, picture yourself in your third's eye like you've got some cat that's in a cat trap and you're like I need to get on a plane with this thing and people are like what is wrong? What are you talking about?

Speaker 3:

oh my god, they literally thought I was nuts, like I was carrying her, and the cat was dirty and mangy and tiny and yeah, I was like a little frantic. I also had I was like getting some award at the university and so like I had to be dressed up and at a location at a certain time I couldn't bail on it, and so I was like trying to do all of this before I went to the awards ceremony and I showed up like looking like crap and it was a whole thing. But now I have the world's most cutest chaotic kitten.

Speaker 1:

Yeah, the, it's a cats and dogs and the pets that we have like their lives are. No, their lives are not cheap. They're important creature world and giving that cat a second chance and now it's gonna know only love and safety, that's a pretty cool little story I know it breaks my heart how she ended up there.

Speaker 3:

So she's such a child.

Speaker 1:

Honestly, I love that cat yeah, so sometimes the difference between cats and dogs is dogs come from XXXY line and I found this cat in behind my house. That's where this cat is.

Speaker 3:

Oh yeah, the cat distribution system definitely answered my prayers. I didn't think it would be this chaotic distribution strategy, but I'm here for it.

Speaker 1:

Yeah, it's how we got our cat. Our cat was a rescue too, ginger. No, that's how we got our cat. Our cat was a rescue too Ginger.

Speaker 3:

No.

Speaker 1:

Yeah, celine, this is the end. Thank you so much for agreeing to be a guest on our show. I know you are, as I have been told, hopping from meeting to meeting in a very busy life. This is right up the alley of the science podcast and a topic that's near and dear to the audience that listens to the show Possibly, probably, hopefully, extending the life of the dogs in our houses that we love so much.

Speaker 3:

Thank, you so much? Yeah, no, thank you um.

Speaker 1:

Where can people find more information about yourself, about loyal? Is there a website? Is there social media?

Speaker 3:

yeah, loyalcom, I think is probably the best. I'm also on twitter, celine hollywa, so if you can figure out how to spell that, you can follow me on twitter if it's okay sorry x.

Speaker 1:

Oh, you can call it twitter. Yeah, we'll have. If it's okay with you, celine, we'll have some links in our show notes that go to your twitter and that is totally fine. Okay, this has been a treat, and thank you so much for giving up your time to chat with us.

Speaker 3:

For sure.

Speaker 1:

That's it for this week's show. Thanks for coming back week after week to listen to the science podcast. Our top dogs get a shout out at the end. It's one of the perks of supporting us. If you want to sign up, check the show notes. Chris, take it away.

Speaker 2:

Amelia Fettig, rhi Oda, carol Hainel, jennifer Challen, linnea Janik, karen Chronister, vicky Otero, Christy Walker, sarah Bram, wendy, diane Mason and Luke Helen Chin, elizabeth Bourgeois, marianne McNally, catherine Jordan, helen Chin, elizabeth Bourgeois, marianne McNally, Catherine Jordan, shelley Smith, laura Steffensen, tracy Leinbach, ann Uchida, heather Burback, kelly Tracy Halberg, ben Rather, debbie Anderson, sandy Brimer, mary Rader. Bianca Hyde, andrew Lin, brenda Clark, brianne Hawes, peggy McKeel, holly Burge, Kathy Zerker, susan Wagner and Liz Button.

Speaker 1:

For science, empathy and cuteness.