Hilary: Over the past 10 years or so, longevity has developed something of a niche, cult following on social media, with prominent figures like tech founder Bryan Johnson. His house has turned into what looks like a pharmacy, as he takes more than 100 pills every day. First one down. Hilary: But getting trials approved for a longevity pill has been nearly impossible. There's no playbook as to how to develop a drug in this space. It's really the Wild West. Now, at least one company might finally be close to approving an anti-aging drug, except it's for dogs. Fun fact: I was embarrassed to say the phrase dog longevity for, like, the first six months of Loyal because of the looks that people would give me. So, why is it so difficult to get a longevity pill approved for humans? I'm Hilary Brueck, and I cover health at Business Insider.

To get a drug approved by the FDA, companies first need to pinpoint which health issue they want to target. It has to be something measurable, like blood pressure or vision. The work starts in preclinical research, phase zero, when scientists test their theories in a lab using computers, cells, or animal models. If those results look good, they submit a plan to the FDA for testing on humans. The clinical trial process then has three phases that can each take years. They answer different questions like how safe is the drug, how effective is it, and how does it work in combination with other treatments, just to name a few. But most drugs don't make it through the entire process, and no drugs targeting aging have even reached the first phase of human testing yet. One big reason for this is we don't yet have a complete picture of how aging really works. That's because aging isn't caused by just one thing.

It's a mix of how our genes, environment, and lifestyle interact, so you can't easily measure it. What people don't realize is that it's this biology of aging that drives the diseases. Hilary: Nir Barzilai is one of many scientists working on drugs that could slow our aging process. As an example, you can be born with genes for Alzheimer's. You need the aging to bring it out. We now understand that we have to prevent this aging. We have to stop this aging, and this is the revolution that we're leading. Hilary: But aging isn't classified as a disease by health regulators, and because of that, it's hard to imagine what a true anti-aging pill would look like. We get really hung up on the idea that we really have to understand these things in very great detail before we can use them. And that's not true for aging. It's not really true for any drug that's been approved.

Matt is one of many scientists who've grown tired of waiting for regulators. He also runs a biotech startup focused on healthy longevity treatments. Matt: We don't really need to understand everything to be able to use these things in an effective way. Graying hair, wrinkling skin, increased body fat, loss of lean mass. Hypothetically, yeah, there's no biological principle that says we can't stop the biological aging process or even in some cases reverse it. But since that isn't being done in humans just yet, some scientists have found more short-lived trial subjects, hoping to see faster results. Matt: Dogs age biologically about seven times faster than people. They get all of the same functional declines and diseases that we do. It just happens faster. Now, it turns out dogs might get a pill before we do. Celine Halioua founded a startup called Loyal that is developing three drugs.

One is for big dogs, which tend to die younger, and two for almost all dog breeds, big to small. I thought you could do it in humans, but I would probably need a billion dollars. I was like, I can't raise a billion dollars. But then we kind of had the crazy idea to work on dog lifespan extension. Hilary: She's a dog lover herself with an 11-year-old rottweiler named Della. It's really these extremely passionate founders and entrepreneurs that are the visionaries that kind of have these ideas that seem absolutely absurd and crazy. It clicked from this feeling like a crazy venture moonshot with a lot of risk behind it to almost more towards the end of inevitable. And she has raised $125 million and attracted some high-profile investors. If you were to tell me six years ago that I was going to invest in a company that was working to extend dog lifespan, I think I would've really, really had to wonder

what were to happen to me over the coming years that would, in essence, come to such a crazy conclusion like that. One of the producers of Lord of the Rings is a big investor in Loyal, and he invested in part because he has a small dog named Pixie who's a senior dog who he loves more than anything. It's not that approving a drug for dogs is necessarily any easier. There are still the same kind of safety requirements as there are for people, but it is a lot faster because dogs live shorter lifetimes. Because it's a brand-new field, the aging field does not have established regulatory paths with regulatory bodies like the FDA, but I think for all those reasons, it also makes it one of the most exciting spaces to watch and be in over the coming decades. Now, the challenge is to convince regulators the drug is working. And they're close. In November 2023, the FDA signaled

a first vote of confidence in Loyal's initial drug, with a reasonable expectation of effectiveness. That's a critical first step towards conditional drug approval for a longevity pill. Halioua says if everything goes well, the first drug might be available by the end of 2025. It's being tested in vet offices around the country right now, and she says her goal is to make it affordable, since many owners pay their vet bills out of pocket. The hope is that it can lead to more breakthroughs for humans too. Dogs are one of the best models of how we age. We've coevolved with dogs. We share an environment with dogs. We get the same age-related diseases they do at approximately the same time in our lifespan. For humans, there might be some answers hiding in cheap generic drugs that are widely available already. Metformin is one of those drugs. It was initially used to treat the flu in Europe.

Nowadays, it's one of the most commonly prescribed drugs for diabetes. It costs, like, $0.20. It's an extract of the French lilac. It's the cheapest drug in the formulary in the United States, or probably all over the world. But metformin goes beyond just controlling blood sugar. In the early 2000s, scientists started noticing that the drug may help reduce some common age-related symptoms because it acts on key metabolic pathways that drive how our body uses energy. These effects could influence some age-related conditions like inflammation, cancer, and fat storage. People on metformin had less cardiovascular disease, they have less cognitive decline in Alzheimer, they have less cancers, their mortality is decreased. And that is because metformin is not really an antidiabetic drug. It's kind of an antiaging drug. We call it gerotherapeutics. But again, metformin is currently approved

for the treatment of diabetes, not for anti-aging purposes. People should always consult a healthcare professional before considering new treatments. But Nir is so convinced that metformin has promise for aging that he started taking it himself. And he imagines a world where, like him, lots of older adults could take this simple $0.20 white pill and potentially see anti-aging benefits like less cancer; smaller amounts of dangerous, visceral belly fat; and just better health. But Nir says the ultimate goal is to see who these different repurposed drugs work best for, then fine-tune the approach in order to find and develop even better new anti-aging drugs. We're not done. We can get better drugs and more drugs and combinations of drugs and drugs that will be better for maybe one disease versus the others. Maybe metformin will give us a couple of years or a few years, but we can go farther. Another drug that's already on the market

and that is gaining popularity right now for anti-aging is called rapamycin. It's an antifungal compound scientists found in the 1960s hiding in a clump of dirt on a remote island in the Pacific Ocean. At first, rapamycin was approved to weaken the body's immune response. It acts on a protein called mTOR. That stands for mammalian target of rapamycin. It's a protein that helps control how cells grow and work. When mTOR is turned down, immune cells slow down and don't react as strongly. This is useful because it prevents the body from overreacting to things like an organ transplant, when the body might try to reject that new organ. So, as per FDA approval, this drug is now given to help transplant patients accept their new organ, like a new kidney. But about a decade ago, researchers saw that mice taking rapamycin had their life expectancy increase by up to 50%.

Then in 2014, another study, this time in elderly people, showed rapamycin improved their immune function. Low doses of rapamycin in aged individuals can actually lead to an improvement in the ability of the immune system to do what it's supposed to do, like respond to vaccines, potentially surveil cancer. In small doses, rapamycin seems to be able to tell old bodies to just kind of settle down, reduce overreaction that leads to inflammation and tissue damage, and key age-related issues. Again, rapamycin has not been approved by the FDA for anti-aging purposes, and robust clinical data is still missing. Even though it could speed things up since these pills have already been tested for safety and proven effective in other areas, it's hard to get independent investors or even big drug companies excited about cheap drugs that are already available. Yet the hype is very much there, at least for influencers like Bryan Johnson.

Bryan: Some pills I take, I take every day. Sometimes I take them twice a day. Sometimes I take once every two weeks, for example, rapamycin. That's also because it's very easy to get these drugs. They're taking advantage of what's called off-label use. Doctors can use any FDA-approved prescription drug as they see fit, writing a prescription for someone even if they don't have the condition listed on the bottle. That doesn't mean people should just run to the pharmacy to get metformin or rapamycin because we don't know enough about how these drugs affect long-term health in the context of aging. Though early research is intriguing, it's still preliminary. Nir too acknowledges there are limitations. Metformin is not good for young people. It decreases their growth-hormone level. It decreases in men the testosterone sometimes. It prevents them to get their muscle

to be as big if they exercise as without metformin. So this is not a drug for young people. This is a drug for somebody who starts to have this breakdown of aging. In the past 150 years, the expected lifespan in the US has doubled. That's mainly because we did a lot of prevention that allowed us to live longer, by developing vaccines, building sewers, and infrastructure for clean water. So we do live longer, but not necessarily better all the way until the end. Now we're more likely to spend those last years struggling with health issues like Alzheimer's, cancer, or cardiovascular disease. Scientists believe that all this research could lead to new, exciting, more profitable pathways for creating effective anti-aging drugs, moving beyond quirky treatments like lilac or dirt fungi to something that truly works for aging. The promise in biotech is that we'll have much more potent drugs so we can extend our health span.

not by a couple of years or five years, but 35 years. That would not only help people live healthier lives, but some argue the benefits to our society would be huge. I think the value from being able to deliver to humans extra productive years and healthy life is almost unquantifiable. There's economical value of not being in the hospital because they travel and they shop and they buy houses for their kids. It's 360, something like that, trillions dollars over 10 years if we just extend health span by a year or two.

Inside The Race To Find The First Anti-Aging Drug | Life Extended | Business Insider

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