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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.

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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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