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On Unexplainable, we spend lots of time talking about everything we don't know, about why we don't know it, about questions.

But there's another science show I love that has a pretty different approach. You might have heard about it.
It's called Science Versus.

And I particularly love listening to this show because they feel like they're almost some kind of complementary kindred spirit.

Like they focus on everything we do know about things like cannabis or heartbreak or even UFOs. But instead of being all like, well, actually,

they do it with humility, with genuine curiosity. And their host, Wendy Zuckerman, is just honestly a joy to listen to.
So we wanted to share one of their recent episodes with you.

I especially like this episode because it kind of picks up where one of ours left off.

We did this episode a few years back about a debate between scientists on how long we might be able to live someday.

And right at the end, we touched on this open question about whether we might not just be able to extend our lives, but extend our youth.

So this week, Science Versus takes that question forward: Can we be forever young?

Hi, I'm Wendy Zuckerman, and you're listening to Science Versus. Today on the show, we're pitting facts against the fountain of youth.

As we find out, is there anything we can do or take to live a longer and healthier life?

For millennia, people have searched far and wide for the elixir of life.

The thing to keep our brains as sharp as attack and our bodies as sprightly as f.

It's said that Gilgamesh searched at the bottom of the sea. Rulers have sent armies to their death, kind of ironically, on the desperate hunt for a magic potion.
Something to help us live forever.

It's like for all of human history, we've been Indiana Jones reaching for the Holy Grail.

So close.

But now

it feels like the search is over.

Now scientists say they've made a breakthrough in the search for a fountain of youth.

If you're looking to increase your longevity and slow your aging, the brain, the body, everything, you've got to check this out.

Millions of dollars are being poured into startups and research labs in the hope of finding the secret to a long and healthy life. And one place they're looking is in the blood of young people.

This made headlines around the globe when millionaire Brian Johnson gave it a go, getting blood plasma transfusions from his teenage son. He even made a short doco about it.
This is amazing.

A long, healthy life united by the beauties of biology. He recognizes how insane this all sounds.
But could he actually be onto something?

And And away from blood boys, these days it feels like if you ask any expert sounding person online what they're taking to keep them young and healthy, one group of supplements is coming up over and over again.

Of the people that I know that look freakishly and unusually young for their age, I cannot get over how many of them have told me that I'm on NAD. I've been supplementing for about seven years now.

I felt like I had more energy. I did notice like my hair and nails are growing at a ridiculous rate.

And finally, some scientists are so excited about a blockbuster drug for diabetes that could fight aging that they're literally singing about it. Makes me feel so young.

It makes me feel so young.

Today on the show, we'll explore the potential powers of young blood, dig into the science on the latest supplements, and we will tell you what actually works.

When it comes to longevity, there's a lot of... This is amazing.

but then there's science.

Science versus longevity is coming up just after the break.

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Welcome back. Today on the show, we're talking about longevity and the anti-aging tricks that are seemingly at our fingertips.
Let's start with the most bonkers. Getting blood from your teenage son.

When that millionaire Brian Johnson did it, people made fun of him because this just feels like the latest in a long line of kooky sh that rich dudes do.

You know, while they're not getting into sketchy submarines, they're getting blood from their teenage sons.

But the thing is, this idea that there is some elixir of life in young blood, it's something that scientists have been looking into for decades.

And one of those scientists is Jim White from Duke University. And he loves researching the potential magic inside young blood.
It's the perfect mix of like sci-fi world meets academic science.

And it's just been an obsession and a fun obsession. So recently, Jim did this study to find out what happens if you get some crotchety old thing and give it a ton of blood from a hot young thing.

Now, Timothy Chalamet was busy, so Jim had to use the next best thing, mice.

And his big question was, if the mouse, the old mouse, gets this young blood for a long time, could we then start slowing all the hallmarks of aging?

The idea is that some old mouse is going to get blood from a younger one for about 12 weeks, which is roughly the equivalent of eight years of human lifespan.

So, how on earth do you get all that blood from a young mouse into an old mouse? Basically, Basically, we join the mice together, surgically join them. Okay.
And I'm going to need some details.

How does that work?

So, a small incision on the flank of the mouse, and then we

to the belly. Is that the flank? Basically, armpit to the hip is kind of the incision.
Right. Right.
You open that up and then you bring that together with the other mouse.

And it's basically like, you know, sewing two pieces of cloth together. Stay with me here

this procedure of stitching animals together is called parabiosis and it sounds pretty gruesome but scientists have actually been doing it for over a hundred years to study all kinds of things so jim does some cutting then connects the skin and other tissues of the mouth which is possible because these mice are basically identical twins so genetically identical to one another it just thinks it's oh that's another part of skin.

That's my skin. And it fuses with it just like you would get a cut on your skin and it would close.
So the blood vessels line up, like if one of the blood vessels would be like, oh no, I'm severed.

Wait, you'll do. Poof.
And then it finds its

beautiful. Basically, they find each other and connect.
What? Without, that's just biology doing cool stuff.

And once biology has done all of its cool stuff and all the blood vessels are fused, then Jim will run these tests to make sure that, yes, the blood of the young mouse is now flowing into the old mouse and vice versa.

And Jim's team also checks to see how rough this whole procedure has been for the mice. So they look for markers of stress.

And weirdly, after this pretty hectic procedure, the mice don't seem that bothered by it all. So they take a pretty harsh surgery pretty well.

And then within just a few weeks they're cruising around together and like nothing happened

yeah so the mousies are walking together and squeaking together and sharing all that blood for 12 weeks and then jim's team will give them an anesthetic and then we detached them and then then we let them live the rest of their days and it's here where jim and his team will really start to take a close look at these mice to find out did all of this work Are the old mice healthier?

And he said that he noticed this difference right away in the older mice.

Because compared to other old mice who went through this hectic surgery but didn't get the young blood, they got up from anesthesia quicker. That, like from the anesthesia of the surgery, yes.

So once we detached them, a couple times, these mice just had a little bit more of a pep in their step. That was the first, huh, moment.

Hmm.

So he lets the mice recover, and then Jim's team starts running some tests on them to find out stuff like, how fit are they? How strong are they? So that's like exercise tests and grip strengths.

Wait, how do you measure a mouse's grip strength? Yes, so it's a little bar, and then the mouse grabs it and you just gently pull the mouse's tail until they release it.

So they tug and you can measure. Oh my God, you're pulling the pull the mouse tail.

Just very slightly. And you can measure how much they pull and then finally, you know, measure what they're resisting against you.

Jim also puts the mice into a little body comp machine. It's like those machines that you get at a fancy gym where it'll tell you how much fat and muscle you have.

And what Jim found is that the old mice that were getting all of that young blood, they had more muscle and they were leaner than other old mice that didn't get the young blood.

Jim could even see a benefit here when he watched these old mice running around a cage and tracked their movements. They were running like laps, literally, around their older cohorts there.
Wow.

They ran better. They were stronger.
And they maintained this. Whereas the old mice just kind of took a dive.
And then did they live longer with all these benefits?

They did. Yep.
They lived, I think we got 9 or 10% extension in longevity. Interesting.

The mice lived about 10% longer than other old mice, which Jim says feels like this true feat of science. You know, we can extend life.
We can do it. For years, you just assumed father time was,

you know, a one-way street, but we can manipulate that a little bit. I think we were a little shocked to see how much we can.
We're able to slow the clock down.

And other studies doing this kind of surgery in mice have found that young blood can help rejuvenate livers and even brain stem cells. So we really wanted to know, how the hell does this work?

Like, what is it in young blood that's doing this?

So that's the magic question.

There's a few ideas running around the cage. Like, this could be about the immune cells that are swimming around in young blood.

The beauty of the youthful immune system is it really doesn't get the credit it deserves. For the most part, our young immune cells cruise around.
It picks off what they call senescent cells.

Senescent cells are basically cells that have gone a little janky, which can happen more and more as we age.

And when you've got more janky cells, it can lead to stuff like inflammation and even cancer. So typically, when these kinds of cells show up, the young immune system kills them.
Gone, get out.

There's other stuff in young blood that could be making a difference here as well. Like it can have higher levels of certain hormones, which have been found to help muscles and neurons grow.

So that is idea number one, that there is something magical in young blood. But it could also be that there's something crappy in the blood of old mice that was kind of getting diluted out.

And Jim saw some evidence of this because the young mice that were getting all of that old blood

accelerate aging. Power of the young blood.

Yes, the power of youth. So what does all this mean for humans? Like if you had some...
some young blood, maybe some very keen students, perhaps, would you be

interested in taking some of their blood? That's, of course, the follow-up question.

I don't think, you know, even a monthly transfusion, because that's where it always says, oh, if we transfuse blood like every month or so. I don't know if that's enough.

Jim says, remember these mice were conjoined for the equivalent of eight human years.

Eight, sharing all that blood. So he's not sure that a couple of pints from a monthly transfusion would work the same magic.
But who knows? Studies in people are just starting to trickle in.

Like one that we found got almost 20 folks with Alzheimer's and gave them the plasma of young men once a week for a month.

They were just doing this test to see if this kind of thing was safe to do, and it was. But they found something surprising.

Some patients seem to be doing a little better at things like feeding themselves or remembering to take their medicine, which is curious, hey?

Researchers are going to keep studying this. But for now,

Jim isn't going to be putting his arm out for a transfusion of that sweet, sweet Gen Z blood.

No, maybe they'll all be laughing when they're 150 years old at everyone that didn't try it. Good for them, but I don't know.
If it works, I hope it does, but.

Okay, so what else have we got? After the break, could the key to longevity be as simple as popping a pill? Some say the secret to a long and healthy life is sitting in your pharmacy right now.

Should you take it? Coming up.

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Welcome back today on the show, the quest for immortality. Or just, you know, to live a long and healthy life.

Now, if you look at basically any health fluencers list of the stuff that they're taking to live a long and healthy life, there's this particular group of supplements that comes up over and over again.

The internet is going nuts for them. It's all over socials, with some calling them a miracle cure for aging.
And they're called NAD boosters.

I shouldn't say NAD rat. NAD is how.

Yeah, I call it NAD. Some people say NAD.
Yeah, but yeah, who says NAD? Because NADS is something else, right?

I think so. Yeah.

Okay, so I just orchestrated a joke so that we could make fun of balls. That's what I did there.

That's all it was. And Melanie McGretal at Penn State University was polite enough to laugh at my joke.
Thank you.

And after we talked about balls, she went on to say that there are feisty debates about these NAD supplements, with some scientists saying that they are dangerous and others saying that they are a game changer.

One person is ringing the alarm and the other person is saying, I take this daily.

And yeah, you see influencers, you see scientists, even various people on reality TV are talking about taking these supplements. So it's everywhere.

So, what are NAD boosters and do they work?

Well, to know what a NAD booster is, first we've got to know what the devil NAD is.

It stands for nicotinamide adenine dinucleotide, and it's this coenzyme that's found in our bodies and is super, super important. So you have NAD in every single cell.

So it lives everywhere in every single tissue? Basically, it's the food that fuels hundreds of reactions throughout your body, including reactions involved in repairing your DNA.

So say if you're out in the sun for a long time, you may get UV damage. Your DNA is squealing.
Oh no, I'm hit. I'm damaged.
So enzymes come to the rescue to fix you up. And those enzymes...

They are going to consume NAD. Oh, so NAD is like the food for the enzymes that we need to repair damage.
Exactly. Yes.

And that's just one thing that it's one of the, yeah, and there's so many others. NAD fuels our energy production, helps control our responses to stress and inflammation.

I mean, you name it, NAD is right there. So when I think about NAD, NAD is playing a vital role in every aspect of biology and chemistry within our bodies.

Is it like having like Usher at Super Bowl? Is that

where it's essential?

For my enjoyment of Super Bowl.

But unlike Usher, NAD is affected by aging. This is how it got wrapped up into this whole anti-aging world in the first place.

Because the thing is, as we get older, older, there's more stuff for NAD to do. We have more inflammation, more DNA damage.

And since NAD is the fuel that feeds all of these reactions, we start running out of it. So as we age, we have less NAD hanging around.
It's not as drastic as...

infrommercials or salespeople make it seem like, ah,

when you're 65, you lost 50% of your NAD. It's not that bad.
You know, it's not that drastic. But is there a steady, slow decline that probably averages around 30%?

Absolutely.

And we think this is a problem. In my studies, lower levels of NAD have been linked to a lot of yucky stuff that happens as we age.

Things like cancer, diabetes, cognitive decline, muscle loss, and hearing loss.

Which is why some people are saying, hey, if dropping NAD levels are linked to all of this nasty stuff, then surely we can fix some of them by bumping up your NAD levels.

And that is what the supplements, the NAD boosters, are supposed to do.

Now, you can't just eat NAD straight. It doesn't work like that.
So instead, the stuff that you can buy, these supplements, are what are called precursors.

So your body takes them and then turns them into NAD. And I know this is going to sound like an alphabet superior, but the two most common supplements like this on the market are known as NR and NMN.

Now, a lot of the studies that test whether they work in people, so they'll give people these supplements and then see what happens, are actually funded by the supplement industry in one way or another.

And even then, overall, A lot of the results from these studies have been pretty meh.

Like, just zooming in on NMN for a second, research has looked into whether taking it affects muscle mass or blood pressure or cholesterol or glucose or insulin.

And they've found that it doesn't help. With NR, which stands for nicotinamide riboside, the research has been a little more promising.

Like several studies have found that they might lower inflammation and blood pressure.

I can say there are seven published human studies showing anti-inflammatory effects of nicotinamide riboside. So the idea of taking these supplements doesn't, it doesn't sound stupid to me, right?

Yeah, I mean, that's the reason why, that's the reason why so many people are doing it. Now I feel a butt coming on.

But yeah.

Should I go out and buy some?

The reason that Melanie is giving us the old

is because She's not sure that these supplements are safe. They haven't been tested on that many people or for that long.

And some early research in mice are showing that perhaps when we take these NAD boosting supplements, maybe we're not just going to boost our NAD, but we might also be bumping up some other stuff that's perhaps not so good for us.

So for example, Melanie's been worrying about this particular enzyme that can get cranked out when mice take these boosters.

And this enzyme can drive changes to our genetics, and it maybe could increase our risk of cancer. And you know, there is this one study that took mice at an increased risk for pancreatic cancer.

It gave them an NAD booster and it found that, yes, it upped their risk for getting cancer.

It's early days here and there's just a lot we don't know about the benefits or the risks. So I asked Melanie.

Given all these unknowns, what do you tell like older people in your life who are like, I want to be healthy for the longest period of of time. Like, should I take these precursors now or not? Yeah,

I've always been hesitant. You think it's too soon? It's too soon for me.
Exactly. That is, that is it.
It's too soon for me.

But a lot of the NAD researchers, I would say, are just running away and selling it. This is an unregulated market, and people are running away with it.

I hope they don't cancel me for this.

So, if you're slamming down the NAD boosters as your holy grail, maybe you chose poorly.

But on the shelf of cups to choose from, and I'm sorry if you haven't watched Ideana Joe's in a while, because this analogy, it's going to get you're going to get lost a little.

But on that shelf of cups to choose from, there is a drug that's been getting a lot of attention, and it looks very tantalizing.

It's attracting headlines like, quote, anti-aging pills are real and some of us are taking them without knowing it.

And if you want to know more about this, there is one guy that everyone is talking to. Neo Baizelai, a professor at Albert Einstein College of Medicine in New York.

And he's been thinking about this longevity stuff for a long time. Even before I became a medical student, you know, when I looked at my grandfather,

I said, what...

You know, what's going on?

How come he, when he was young, he had all those stories of bravery and achievement, and he barely can walk now?

And so, Neil wanted to know: how can we stop this from happening? Which took him to this drug that so many people are excited about. It's called metformin.

It comes from this gorgeous purple flower called the French lilac, and people have actually been using it for ages, saying it can work for all kinds of things.

Metformin was used by mothers, grandmothers, healers to treat osteoarthritis, to prevent flu, lots of stuff.

But today, metformin is prescribed for type 2 diabetes because it helps control blood glucose levels. And it is a blockbuster drug.
Over 150 million people around the world take it.

But more recently, scientists like Nio have started thinking that maybe this drug could do a whole lot more. Perhaps it could boost our longevity.

And one paper in particular kind of jump-started this. There was a study that really excited me.
It was kind of a shocking study because it took people that are treated in pharmacies in the UK.

They got around 180,000 people. And the researchers said, Let's look at the people who had diabetes.
Some of them were treated with metformin. and others were treated with another drug.

They followed people for several years and found that those who were taking metformin were less likely to die by the end of the trial compared to those who were taking a different diabetes drug.

And it was by around a third, which is quite a lot. And since then, other research has shown similar things, that metformin helps people with diabetes to live longer.
And Nier says it's not only that.

People on metformin who have diabetes have less cardiovascular disease, they have less cancers, they have less cognitive decline, Alzheimer's.

Early research in mice has also found that metformin can help with a bunch of other stuff that's linked to aging, including reducing inflammation and boosting antioxidants, which could improve the health of our blood vessels.

And Nia's like, well, if this drug is so great, at least for people with diabetes, what about the rest of us? All of a sudden, we said, you know what? Non-diabetics could do better on metformine.

And there is a little bit of evidence for this. So, like in that big UK study, you know, the one that shocked Nia,

well, they found something pretty odd in it. And it's this.

So people who have diabetes but were taking metformin actually lived slightly longer than those who did not have diabetes, what we tend to think of as the healthy controls.

Now, it wasn't by a lot, but it was enough for Nia to take notice.

And that was kind of really cool. I mean, diabetes decrease lifespan, okay?

So we are expecting them to do worse, but they're on metformin and yet they do better.

And it's studies like this that are really driving these exciting headlines that are saying that metformin is the new anti-aging pill of our lifetime.

But the thing is, there's been some newer research that's gotten a lot less buzz. And if we were writing the headlines for these newer studies, it would be, metformin doesn't make you live longer.

Like these scientists out of Denmark, they tried to replicate that big UK study.

And they actually found the opposite thing, that people taking metformin for diabetes didn't live longer than healthy controls, which is exactly what you'd expect.

Another huge study out of the UK compared people taking metformin for diabetes to another group without diabetes and found that while in the first three years, the metformin group seemed to be living longer, after five years, the trend reversed.

For Nia,

he told us that he doesn't think these papers are the nail in the coffin for Metformin. And he's not losing hope.
It's not about hope, it's about evidence.

Nia says that what we really need now is a randomized controlled trial in older people who don't have diabetes. And that study is exactly what he's planning to do.

And this would really help us to know if Metformin actually does anything for aging if you don't have diabetes.

In the meantime, though, what metformin has going for it, unlike say NAD boosters, is that metformin is an FDA-approved drug. And we know that it's pretty safe.

Yeah, there are some side effects to look out for, like nausea. Plus, a recent study in men found that maybe it was linked to birth defects in their kids.
We're not really sure.

But if you're not trying to father a child anytime soon, it seems pretty low risk.

And Nia, he actually takes it. I do.
I do. I started this for pre-diabetes, which I'm not anymore for 10 years, but it has measurable effects on my health.
Makes me feel so young.

It makes me feel so young.

Okay, the end of the episode is nigh. And here's where we're at.
We're still waiting for the final word on Medformin. This drug, it still could be exciting, but we're going to have to wait and see.

As for NAD boosters, we're going to give them a miss.

So is there anything else that we've got?

That's what I asked Jim, you know, that researcher that sews the mice together. When people ask that, they have like their pen out.
Like,

you must know something from your studies. Like, you know, what do you take? What supplements? You must take all of them.
No, I don't. So what do you do? What do you tell people?

Yeah, this is the part where everyone, yeah, everybody kind of, this is like the womp womp

response, right? I tell people it's like exercise, diet. And they're like, oh, we've been hearing that all the time.
Who wants to do that? Boo.

Yes, you've heard about these things, but we'll say them again. Stuff like a healthy diet where you're eating fresh fruit and veggies and whole grain and olive oil and fish and nuts.

That has been linked to living longer.

With exercise, while there is actually some debate about whether it can make you live longer, we have good research to show that it can make you healthier for the years that you've got.

And there's a few other things that can help you win the longevity lottery. So studies have found that being less stressed may save you from dying from heart disease.
I hate this one too.

I get stressed all the time, but

stress management, I guess. We should give it a go.
Something that's more fun to give a go is being more social, seeing mates, trying to avoid loneliness. That's been linked to longevity.

And one of the most surprising longevity boosters that we came across was hearing aids.

Yeah, a study published this year found that people with hearing loss who regularly used hearing aids were 24% less likely to die compared to similar people who didn't use them.

We're not exactly sure why that is. And finally, don't smoke.

One huge study estimated that if you can quit before you're 35, it can add around seven years to your life, which is more years than you'd get from having a young mouse sewn to your belly.

So there you have it: diet,

exercise,

stress management.

But wait, what if we said it in a more excited way? Exercise, diet, stress management. Yay! Yay!

That's Science Versus.

Hello.

Hey, Michelle Dang, producer at Science Versus. Hey, Wendy.
So how many citations are in this week's episode? There are 84 citations. 84.

And if people want to see them in all of their glory, I just, I like really feel in this episode all those 84 citations.

Where should they go to find them? Head over to the show notes and click on our transcript and you can see all 84 citations.

Oh, and for people who are very interested in living for a long time, there is one, one more big thing that we didn't cover in this episode that people say can increase your longevity. Oh, which one?

And that is fasting. And so we have actually dedicated an entire episode to fasting.
We covered it several years ago.

We've updated the science and it's going to come out in just a couple of weeks, our episode on intermittent fasting.

But for now, it's time to go to bed. Thanks, Michelle.
Thanks, Wendy. Bye.

This episode was produced by Michelle Dang and me, Wendy Zuckerman, with help from Meryl Horne, Rose Rimmler, and Joel Werner. We're edited by Blythe Terrell.
Research help from Timmy Broderick.

Fact-checking by Eva Dasher. Mix and sound design by Bobby Lorde.
Music written by Bumi Hidaka, Emma Munger, Peter Leonard, So Wiley, and Bobby Lord.

A special thanks to all of the researchers that we spoke to for this episode, including Dr. Janet Choi, Dr.
Gideon Meyowitz-Katz, and Dr. Zhu Li.

A special thanks to the Zuckerman family and Joseph Lavelle Wilson. I'm Wendy Zuckerman.
I'll back you next time.

Support for this show comes from S. Steve Johnson.
We've all been there. Choosing not to wear your new white shoes because there's a 10% chance of rain.

Bending awkwardly over the tiny coffee table to enjoy a sip of your latte.

Not ordering the red sauce. Those feelings of dread are what we call stainsiety.

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