S03E74 - It's a Dog's Life: A New Anti-Aging Drug for Our Best Friend?

What if man’s best friend could live longer? We’re about to delve into the groundbreaking science of LOY-1, a new drug with potential to extend the lifespan of dogs. We explore why this drug, which lowers IGF-1 levels in the body, could be a game-changer not just for our dogs, but for human longevity as well. However, with every new discovery comes controversy and ethical concerns. How much would you pay for a longer life for your dog, or for you?

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S03E74 - It's a Dog's Life: A New Anti-Aging Drug for Our Best Friend?

[00:00:04] Sam Rhee: Do you own a dog, or have you ever owned a dog? How much would you pay for one extra year of life for your dog? I had too many dachshunds, or wiener dogs as they're commonly called, as pets years ago, and I loved them very much, and they were inseparable from us for over ten years. They were an essential part of our own young adult lives, and they moved with us from New York, to Michigan, to California, and then finally to New Jersey.

And my two dogs grew up from the littlest, cutest puppies to crazy doggos with non stop energy. But then, at some point, they finally got old and grizzled, and had gray hair and stiff joints. And when they finally passed away, it was so heartbreaking and difficult that we decided never to get another dog because we didn't think we could go through that again.

Many pet owners go through the same heartbreak when their pets die, and they will spend money, sometimes breathtaking amounts, for their beloved furry animals. I know of a family that recently paid $10,000 for gallbladder surgery for their dog, plus another $3,000 for post op care after the surgery.

Now, you may or may not think that that's just crazy money to spend on a pet, but there is a drug company out there that's willing to bet that dog owners will pay, possibly a lot of money, for a drug that will lengthen dogs lives.

[00:01:25] Sam Rhee: A company named Loyal, which is a subsidiary of a biotech firm Cellular Longevity, after four years of research, has just met the first condition for expanded conditional approval from the FDA, allowing them to start larger clinical trials in 2024 or 2025 for a drug LOY 1, which they think can increase the lifespan of dogs.

This is the first life extending drug, human or animal, ever to get this far with the FDA. So what is this drug? Will it work? Will it get FDA approval? Will humans be next? Let's talk about LOY 1 and the possibility of a best boy fountain of youth.

So what is this drug, LOY 1, that this company's testing? The company Loyal says this medication reduces IGF 1 levels in the body. IGF 1, which is short for insulin like growth factor, is a hormone produced in the liver by both animals and humans. IGF production is directly stimulated by growth hormone, which in humans is known as HGH, which is secreted by the pituitary gland.

Growth hormone increases IGF levels, which then stimulates cellular growth and production, especially in muscle, cartilage, bone, and other tissues in the body. So for most of our lives, having increased growth hormone and therefore increased IGF levels is generally considered desirable.

High levels of IGF are responsible for the sudden growth spurt during puberty. And IGF increases lean muscle mass, decreases fat, and increases the number of new neurons in the brain.

Conversely, having a genetic mutation that causes IGF or growth hormone deficiency results in dwarfism in humans. And there is an FDA approved recombinant form of IGF, which is given to pediatric patients with IGF deficiency, who suffer from severely short stature and fatigue. And in dogs, breeders have exploited a rare IGF deficiency mutation to create the toy dog breeds.

Bodybuilders and athletes have long taken HGH and IGF as performance enhancing drugs. The deer antler velvet sprays that were all the rage in sports world ten years ago, they all contained high amounts of IGF. And currently IGF is banned by nearly every professional sport as a prohibited substance.

When you look at the lifestyle factors that are known to decrease IGF and HGH levels in humans, these are all things that are universally acknowledged to be bad. Increased body fat, excess sugar intake, poor sleep, lack of exercise, increased stress, poor nutrition. All of these contribute to low IGF and human growth hormone levels in the body.

And health gurus are always harping on us to try to help us increase our natural growth hormone and IGF levels to be healthy. Plus, anti aging clinics have been pushing HGH treatment for decades, because we know that as we get older, decreased IGF levels causes muscle atrophy, loss of neurons, and thinner skin.

So if IGF is supposed to actually be good for you, how do we get to a point where this company, Loyal, is looking at a drug that decreases IGF levels in the body?

Well, it's kind of a complicated road, so let's just take a quick look at this anti aging research.

So you may know that scientists have for a long time known that calorie restriction, or reducing the amount of food eaten, is one of the most consistent means of dramatically increasing lifespan by 50 percent or more for many research species, including worms, fruit flies, yeast, and mice.

On a molecular level, there are a number of cellular pathways that scientists have been investigating as a possible cause for this increased longevity.

Decreased growth hormone and IGF levels were seen in these calorie restricted animals. And so that was one possibility that they started looking at. They started developing animals with mutations. including mice with IGF deficiencies. And some of these mutations resulted in animals that lived as long as regular calorie restricted animals.

Research with calorie restriction in humans is complicated because nobody is going to starve themselves so severely to live longer. At least, not most normal people. But there are some interesting observational data in humans where they found having low levels of IGF as a younger adult, under the age of 50, caused an increase in death and disease.

But over the age of 50, a lower IGF level is actually beneficial for health. So maybe IGF is needed when we're younger, but could it actually be harmful as we get older? There's a lot more that has to be researched here.

I would say think twice about considering HGH as you get older, because that might not be a way to live longer.

So what is the thinking about why IGF may be a problem as we get older? Nobody really knows, but it could be that the anabolic effects of IGF result in higher cellular metabolism and increased oxidative stress and inflammation, and these higher metabolic processes and increased cellular stress products from high IGF levels over the long term might increase the risk of diseases resulting from chronic inflammation. Researchers have been looking for ages to try to combat this possible issue of chronic inflammation by testing all sorts of antioxidant compounds and drugs.

So by lowering IGF levels, you avoid having to take as much antioxidants because there's less level of cellular stress products in the system. But we'll just have to wait and see what comes next.

But for now, getting back to dogs. The company Loyal is targeting big dogs with their LOY drug. Big dogs are breeds like Great Danes, Mastiffs, St. Bernard's, Irish Wolfhounds, Newfoundlands, and the like. On average, large breeds live only 7 to 10 years, while small dogs like Chihuahuas live double that. And the reason that these large breeds are so big is because of their increased IGF levels, up to 28 times more than small dogs.

So in their initial study, the company Loyal dosed 130 adult dogs with LOY 1, which resulted in successfully lowering these large dog IGF levels to those of medium sized dogs. Now this drug is designed to be injected by a veterinarian every three to six months, and supposedly the company reported the only side effect was some loose stool for a couple days, in a few dogs, and nothing else.

So their next step is a bigger study with a thousand large breed adult dogs at least seven years old, they will either inject the drug or placebo into them. And they hope to finish this study by 2025 and get FDA approval and start selling the drug by 2026, which I think is a pretty aggressive schedule.

To me this is a pretty big Hail Mary shot from a biotech firm. I mean, who knows if this drug will work, or even be safe? I've seen so many drugs even get FDA approval and then be withdrawn after larger numbers of subjects started taking them. What if the drug causes these dogs to just shrivel up, get weak, and decrepit from a lack of IGF? Or they have diarrhea all the time?

And if this drug does even work, what will the cost be, and how much benefit are they going to get? There are also a number of other drugs that researchers are trialing on dogs as well, including rapamycin, which is a well known immunosuppressant medication, which some anti aging fanatics have already been trying off label for themselves already.

And this is an extremely complicated field, and I think we're just starting to scratch the surface practically about what is involved in aging and longevity. Now, I am glad that there are people out there that are looking to find drugs that might help us extend the lifespan of dogs, and potentially us humans.

And I do wonder whether I will live long enough to see any of these drugs really work. And the mind boggles with the science fiction possibilities as we get started down this path.

But at the end of the day, we know our loved furry companions aren't going to live forever. And neither will we. We spent some amazing years with our two wiener dogs, and those memories are very precious to me. Isn't what's most important is how we choose to spend our time in our lives with our dogs?

Whether they're made shorter or somewhat longer by some drug? As they always say, it's not the years in your life that matter, it's the life in your years. I hope we don't forget that. Thank you.

My weekly thankful is for my medical school class, who recently established the Class of 1996 Greg Grove Memorial Student Mental Health Fund, which helped to establish an educational program at Columbia to help medical and dental students identify, understand, and respond to signs of mental illness and substance abuse disorders in their classmates and others.

The fund helps to supplement existing services with programming that fills the gap. And the inaugural Mental Health First training sessions were held recently, resulting in 34 students, faculty, and staff being certified. And the feedback was overwhelmingly positive with several faculty members wishing to be trained as instructors.

If you saw or heard my podcast last week, you know how I talked about mental toughness and the difficulty of dealing with some of these stressful experiences in residency and life.

I'm so proud of my class for memorializing our classmate, Greg. and for making a difference so that the next classes of medical providers can be healthier and better people.

Thanks again for watching and listening, and please, as always, DM me @BotoxAndBurpeesPodcast on Instagram, or leave a comment, YouTube.com/@BotoxAndBurpees. Thank you.