Inside the race to find the first antiaging drug

Business Insider

Could one pill help us live longer? Scientists and investors are racing to find a drug to slow aging, trying things like metformin and rapamycin. But the breakthrough might not come from humans.

Transcript

00:00Over the past 10 years or so, Longevity has developed something of a niche cult following

00:05on social media, with prominent figures like tech founder Brian Johnson.

00:10His house has turned into what looks like a pharmacy, as he takes more than 100 pills

00:15every day.

00:16First one down.

00:17But getting trials approved for a Longevity pill has been nearly impossible.

00:21There's no playbook as to how to develop a drug in this space.

00:25It's really the Wild West.

00:27Now at least one company might finally be close to approving an anti-aging drug.

00:32Except it's for dogs.

00:33Fun fact, I was embarrassed to say the phrase dog longevity for like the first six months

00:38of Loyal because of the looks that people would give me.

00:41So why is it so difficult to get a Longevity pill approved for humans?

00:45I'm Hilary Brick and I cover health at Business Insider.

00:49To get a drug approved by the FDA, companies first need to pinpoint which health issue

00:53they want to target.

00:55It has to be something measurable, like blood pressure or vision.

01:00The work starts in preclinical research, phase zero, when scientists test their theories

01:05in a lab using computers, cells, or animal models.

01:10If those results look good, they submit a plan to the FDA for testing on humans.

01:15The clinical trial process then has three phases that can each take years.

01:19They answer different questions like how safe is the drug, how effective is it, and how

01:25does it work in combination with other treatments, just to name a few.

01:29But most drugs don't make it through the entire process, and no drugs targeting aging

01:34have even reached the first phase of human testing yet.

01:37One big reason for this is we don't yet have a complete picture of how aging really

01:41works.

01:42That's because aging isn't caused by just one thing.

01:46It's a mix of how our genes, environment, and lifestyle interact.

01:50So you can't easily measure it.

01:54What people don't realize is that it's this biology of aging that drives the diseases.

02:00Nir Barzilai is one of many scientists working on drugs that could slow our aging process.

02:04As an example, you can be born with genes for Alzheimer's.

02:09You need the aging to bring it up.

02:12We now understand that we have to prevent this aging, we have to stop this aging, and

02:17this is the revolution that we're leading.

02:20But aging isn't classified as a disease by health regulators.

02:23And because of that, it's hard to imagine what a true anti-aging pill would look like.

02:29We get really hung up on the idea that we really have to understand these things in

02:33very great detail before we can use them.

02:36And that's not true for aging, it's not really true for any drug that's been approved.

02:40Matt is one of many scientists who've grown tired of waiting for regulators.

02:44He also runs a biotech startup focused on healthy longevity treatments.

02:49We don't really need to understand everything to be able to use these things in an effective way.

02:54Graying hair, wrinkling skin, increased body fat, loss of lean mass.

03:01Hypothetically, yeah, there's no biological principle that says we can't stop the biological

03:07aging process, or even in some cases, reverse it.

03:10But since that isn't being done in humans just yet, some scientists have found more

03:14short-lived trial subjects hoping to see faster results.

03:18Dogs age, biologically, about seven times faster than people.

03:23They get all of the same functional declines and diseases that we do, it just happens faster.

03:28Now it turns out dogs might get a pill before we do.

03:30Celine Hallyua founded a startup called Loyal that is developing three drugs.

03:35One is for big dogs, which tend to die younger.

03:38And two, for almost all dog breeds, big to small.

03:41I thought you could do it in humans, but I'd probably need a billion dollars.

03:44I was like, I can't raise a billion dollars.

03:48But then we kind of had the crazy idea to work on dog lifespan extension.

03:52She's a dog lover herself, with an 11-year-old Rottweiler named Della.

03:57It's really these extremely passionate founders and entrepreneurs that are the visionaries

04:01that kind of have these ideas that seem absolutely absurd and crazy.

04:06It clicked from this feeling like a crazy venture moonshot with a lot of risk behind

04:11it to almost more towards the end of inevitable.

04:14She has raised $125 million and attracted some high-profile investors.

04:19If you were to tell me six years ago that I was going to invest in a company that was

04:23working to extend dog lifespan, I think I would have really, really had to wonder what

04:30were to happen to me over the coming years that would change, you know, in essence come

04:34to such a crazy conclusion like that.

04:36One of the producers of Lord of the Rings is a big investor in Loyal.

04:41And he invested in part because he has a small dog named Pixie, who's a senior dog, who

04:47he loves more than anything.

04:49It's not that approving a drug for dogs is necessarily any easier.

04:53There are still the same kind of safety requirements as there are for people.

04:57But it is a lot faster, because dogs live shorter lifetimes.

05:00Because it's a brand new field, the aging field does not have established regulatory

05:04paths with regulatory bodies like the FDA.

05:08I think for all those reasons, it also makes it one of the most exciting spaces to watch

05:11and be in over the coming decades.

05:13Now the challenge is to convince regulators the drug is working.

05:17And they're close.

05:19In November 2023, the FDA signaled a first vote of confidence in Loyal's initial drug

05:24with a reasonable expectation of effectiveness.

05:27That's a critical first step towards conditional drug approval for a longevity pill.

05:31Halyua says if everything goes well, the first drug might be available by the end of 2025.

05:37It's being tested in vet offices around the country right now.

05:40And she says her goal is to make it affordable, since many owners pay their vet bills out

05:45of pocket.

05:47The hope is that it can lead to more breakthroughs for humans, too.

05:50Dogs are one of the best models of how we age.

05:53We've co-evolved with dogs, we share an environment with dogs.

05:57We get the same age-related diseases they do at approximately the same time in our lifespan.

06:04For humans, there might be some answers hiding in cheap generic drugs that are widely available

06:08already.

06:09Metformin is one of those drugs.

06:11It was initially used to treat the flu in Europe.

06:14Nowadays, it's one of the most commonly prescribed drugs for diabetes.

06:17It costs like 20 cents.

06:20It's an extract of the French lilac.

06:22It's the cheapest drug in the formulary in the United States, or probably all over the

06:27world.

06:28But metformin goes beyond just controlling blood sugar.

06:32In the early 2000s, scientists started noticing that the drug may help reduce some common

06:36age-related symptoms, because it acts on key metabolic pathways that drive how our body

06:41uses energy.

06:42These effects could influence some age-related conditions like inflammation, cancer, and

06:46fat storage.

06:48People on metformin had less cardiovascular disease.

06:50They have less cognitive decline in Alzheimer's.

06:52They have less cancers.

06:54Their mortalities decrease.

06:56And that is because metformin is not really an anti-diabetic drug.

07:01It's kind of an anti-aging drug.

07:03We call it gerotherapeutics.

07:05But again, metformin is currently approved for the treatment of diabetes, not for anti-aging

07:10purposes.

07:11People should always consult a healthcare professional before considering new treatments.

07:14But Nir is so convinced that metformin has promise for aging that he started taking it

07:19himself.

07:20And he imagines a world where, like him, lots of older adults could take this simple 20-cent

07:25white pill and potentially see anti-aging benefits like less cancer, smaller amounts

07:30of dangerous visceral belly fat, and just better health.

07:34But Nir says the ultimate goal is to see who these different repurposed drugs work best

07:39for, then fine-tune the approach in order to find and develop even better, new anti-aging

07:45drugs.

07:46We're not done.

07:47We need to get better drugs, and more drugs, and combination of drugs, and drugs that will

07:52be better for maybe one disease versus the others.

07:56Maybe metformin will give us a couple of years, a few years, but we can go farther.

08:02Another drug that's already on the market and that is gaining popularity right now for

08:05anti-aging is called ravamycin.

08:09It's an antifungal compound scientists found in the 1960s, hiding in a clump of dirt on

08:14a remote island in the Pacific Ocean.

08:17At first, ravamycin was a proof to weaken the body's immune response.

08:21It acts on a protein called mTOR.

08:24That stands for mammalian target of ravamycin.

08:27It's a protein that helps control how cells grow and work.

08:31When mTOR is turned down, immune cells slow down and don't react as strongly.

08:37This is useful because it prevents the body from overreacting to things like an organ

08:41transplant, when the body might try to reject that new organ.

08:46So as per FDA approval, this drug is now given to help transplant patients accept their new

08:50organ, like a new kidney.

08:53But about a decade ago, researchers saw that mice taking ravamycin had their life expectancy

08:57increased by up to 50%.

09:00Then in 2014, another study, this time in elderly people, showed ravamycin improved

09:05their immune function.

09:07Low doses of ravamycin in aged individuals can actually lead to an improvement in the

09:13ability of the immune system to do what it's supposed to do, like respond to vaccines,

09:18potentially surveil cancer.

09:20In small doses, ravamycin seems to be able to tell old bodies to just kind of settle

09:24down, reduce overreaction that leads to inflammation and tissue damage and key age-related issues.

09:32Again, ravamycin has not been approved by the FDA for anti-aging purposes, and robust

09:37clinical data is still missing.

09:40Even though it could speed things up, since these pills have already been tested for safety

09:43and proven effective in other areas, it's hard to get independent investors or even

09:48big drug companies excited about cheap drugs that are already available.

09:52Yet the hype is very much there, at least for influencers like Brian Johnson.

09:56Some pills I take, I take every day.

09:59Sometimes I take them twice a day.

10:00Sometimes I take once every two weeks.

10:01For example, ravamycin.

10:02That's also because it's very easy to get these drugs.

10:05They're taking advantage of what's called off-label use.

10:09Doctors can use any FDA-approved prescription drug as they see fit, writing a prescription

10:13for someone even if they don't have the condition listed on the bottle.

10:17That doesn't mean people should just run to the pharmacy to get metformin or ravamycin,

10:21because we don't know enough about how these drugs affect long-term health in the context

10:25of aging.

10:26Though early research is intriguing, it's still preliminary.

10:30Dr. Neer Tu acknowledges there are limitations.

10:33Metformin is not good for young people.

10:35It decreases their growth hormone level.

10:37It decreases in men the testosterone sometimes.

10:40It prevents them to get their muscle to be as big if they exercise as without metformin.

10:48So this is not a drug for young people.

10:52This is a drug for somebody who starts to have this breakdown of aging.

10:58In the past 150 years, the expected lifespan in the U.S. has doubled.

11:03That's mainly because we did a lot of prevention that allowed us to live longer.

11:07By developing vaccines, building sewers, and infrastructure for clean water.

11:13So we do live longer, but not necessarily better all the way until the end.

11:19Now we're more likely to spend those last years struggling with health issues like Alzheimer's,

11:23cancer, or cardiovascular disease.

11:28Scientists believe that all this research could lead to new, exciting, more profitable

11:31pathways for creating effective anti-aging drugs.

11:35Moving beyond quirky treatments like lilac or dirt fungi to something that truly works

11:41for aging.

11:43The promise in biotech is that we'll have much more potent drugs so we can extend our

11:50health span not by a couple of years or five years, but 35 years.

11:53That would not only help people live healthier lives, but some argue the benefits to our

11:57society would be huge.

11:59I think the value from being able to deliver to humans extra productive years and healthy

12:06life is almost unquantifiable.

12:09There's an economical value of not being in the hospital because they travel and they

12:13shop and they buy houses for their kids.

12:16It's 360 something like that, trillions of dollars over 10 years if we just extend health

12:22span by a year or two.

12:27www.microsoft.com

12:29www.microsoft.com

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