This Compound Reverses Immune Aging — Here's Why Scientists Are Stunned

So urolithin A has this remarkable ability to activate mitophagy. Mitophagy is not sort of the, as the term implies, it's eating mitochondria, but it doesn't eat them discriminately. It eats the old defective mitochondria, which is absolutely remarkable.

It's such an important kind of framework to think about the sort of energy of the cell because it really runs everything. Yes. And we kind of do know that everything that impacts aging also impacts the mitochondria and vice versa. And, and what we, there are levers though to really take care of your mitochondria. Yes. We talked about NAD on our last podcast, but there's other compounds that induce mitophagy and that are, when we mentioned postbiotics earlier, which are essentially compounds that you eat from food that get metabolized by your bacteria and they produce downstream molecules that have function in the body, which I think is a miracle. Just when you think conceptually about it, that you eat stuff and then it creates like a, literally a medicine that it turns on different signaling systems in your body to help you repair, renew. And I, and I think from my perspective, and I, it sounds like you think the same way, when I think about aging, I think, you know, the body has these innate systems of repair, renewal, regeneration. We just burden them.

Yes.

And we don't take care of them.

Yes.

And that's why we age faster. And instead of focusing on treating disease, if we focus more on our regenerative renewal and repair systems, we do a lot better. And so the way in is through some of these food molecules. And I, I, I, I call it, I, I have this joke, I call it a symbiotic phytoadaptation. We symbiotically evolved with plants and use their compounds to regulate our biology. And 'cause we're lazy, like we don't make vitamin C, so we get vitamin C from food. We don't make, for example, one of these postbiotics called urolithin A, so we make it from pomegranate or other ellagitannins that are in, you know, walnuts or berries or whatever. So kind of help us understand how, how, for example, this molecule urolithin A, which you published on, it's, yeah. And we'll link to the papers in the show notes. And which I, by the way, take every day because the literature's impressive on it. What does it do and, and why, why is it getting so much attention now? And, We've kind of learned about it more in the context of exercise, improving exercise capacity, VO2 max, and fitness, and muscle health, and mitochondrial health. But it does have a link to immune system. So what is it and how is it linked to these things that we just talked about? So I'm wrapping back up with immune function, the gut, and mitochondria, because it's like one thing.

It's a really cool story because it's one really, I would call it, of sort of a human ingenuity in some way. We've known for a long time that pomegranate juice, juice is actually healthy for people. And there's a whole, you know, there've been studies showing that consumption of pomegranate juice is actually, confers some health benefits. What was not clear is what the mechanism. So some scientists, a good friend of mine, Johan Auerichs, who works in Lausanne, actually went and looked for what is in pomegranate juice. And they found these ellagitannins, these compounds. What they also realized is that these compounds are not acting by themselves. They are actually metabolized by your microbiome. And the product that is made by your microbiome is called urolithin A. Okay, now the catch is only about 35 to 40% of people's microbiome, because remember, all of our microbiomes are different, and some 60% of people's microbiome is not able to make that conversion.

So we've trashed them because of our diet, because of antibiotics, because of toxins. All this stuff. So we kind of—

Having a rich, you know, most of us have more than 1,000 different species of bacteria in our guts. And the problem, the complicating factor is most of us have different species. So you cannot compare your microbiome and mine, even though we might both be very healthy. But they can change.

Like I've seen the study, you have people on a vegan diet or feel a meat paleo diet, their microbiomes, literally in the same person, will change. Yeah.

We don't know how to read it well, but we know certainly what upstream factors can actually yield a really complex and rich microbiome. Yeah, so this is a clear example of where sort of human ingenuity has been able to identify a single molecule, urolithin A, that is the result of an input from a food product, from a plant, pomegranate juice. It gets transformed by a fraction of us into a product that has immense benefits. So company was founded based on this, Amazantis, that actually sells this product. And has, we've been working with them. I say, I mean, full disclosure, I sit on the board of that company as a scientific advisor, but I always tell people I don't sit on the board of supplement company if I don't believe in the science. And if they're not willing to actually conduct clinical trials. And it's one thing I think is commendable for Amazent is they've been going through clinical trials one at a time to actually document and prove the efficacy of what they're doing.

I agree. And they're a sponsor of the podcast and that's why also I don't, Let everybody sponsor my podcast. You imagine all of you will ask me because I think I want stuff that I know has legitimate science behind it and anyone that's published in major journals like New England Journal or JAMA or others. So I think this is important.

So to me, I'm not opposed to supplements, but we have to apply to them the same kind of standards that we've applied to generating all of the drugs that we have and that's how medicine has moved forward. So that being said, we've worked with them on a couple of studies. We still have another study going on with them. So urolithin A has this remarkable ability to activate mitophagy. And mitophagy is not sort of the, you know, as the term implies, it's eating mitochondria, but it doesn't eat them discriminately. It eats the old defective mitochondria, which is absolutely remarkable. So when you do this, actually one of the studies that we've done was looking at the human immune system of all the people on urolithin A. And what we found is really actually significant effect even within one month of administration of urolithin A. We saw some, I would say, what anybody would call a rejuvenation of the immune system.

Yeah. I mean, I think, you know, early on when I looked at the data, this is years ago, I got excited about it. I saw like a reduction in CRP, which is a very crude marker of inflammation. And we measure with Function Health, but there's even better markers. But how, what are the things that you looked at that indicated that it helped to reduce the inflammation process?

Yeah, actually in our case, we— well, some cytokines, we measured the presence of different cytokines, TNF-alpha, IL-6, IL-1, and I don't remember exactly which ones were changed, but some of them were.

And cytokines are the messenger molecules of the immune system.

Exactly. And the IL-1, IL-6, TNF-alpha are pro-inflammatory molecules. So the higher the level, the higher inflammation. What we focused on in my lab and And with our core at the back was on looking at the adaptive immune system. And what we saw was actually quite interesting. We saw an increase in naive T cells. So these are the precursors that are really critical at generating an adaptive immune response. We saw a whole series of other changes in—

And just in English, naive T cells are kind of cells that haven't made the antibodies yet. They haven't kind of—

They haven't been activated to—

To develop antibody.

The T cells. The B cells would be making the antibodies. So these are the T cells.

That cause the B cells to make the antibodies.

They help, but they also by themselves can generate what we call cytotoxic T cells, CD8 T cells, which are the other. So the arm, the innate immune system, the adaptive immune system has two arms, T cells and B cells. The T cells are making, actually they can kill bad cells. The B cells can actually secrete the antibodies, which help in the immune response.

And so the urolithin A AI works on the T cells.

It worked on the T cells and actually increased the ability of these T cells to recognize their targets. Now, this has implication not only for the person who's taking this, but think about, you might have heard about the CAR T cells that are used now for cancer cells, where we can extract T cells from a patient and educate them to selectively kill tumor cells. And the problem is that as you get older, your ability to make, to reeducate these T cells goes down. And so this would have even implication for cancer.

Yeah.

Because they did it in vitro and show that these CAR T cells were actually more effective.

So in other words, it makes immunotherapy work better.

Exactly.

If you improve and rejuvenate your T cells.

Totally.

Before you start to sort of target them for cancer. That's amazing. So how does your Lanthanum affect like the, the whole process of longevity, the muscle, the the inflammation? Like, what do we know about it?

Mitochondria are not just present in the immune system, they're present in every cell. And so think about the concept of—

Except for red cells.

Except for red cells, exactly. Yeah, they don't have a nucleus, they don't have mitochondria. I think they have mitochondria.

Oh, they do?

When we think about mitochondrial function, it's not restricted to the immune system. It's pretty much every cell that has to balance repair and dividing and moving forward. So when we when we think about urolithin A's effect, they're going to be pretty much across the whole organism. And I mean, we've focused so far on the muscle where we could see increased endurance in people, actually on humans on urolithin A. We've seen increased immune responsiveness. My prediction is that when we start looking in the brain, we might see increased performance, increased memory, and so on. Not been proven yet, but, you know, this is a molecule that's not just targeting the immune system or an organ.

You call it pleiotropic.

It's pleiotropic. And I think my prediction, I don't think this has been shown yet, but you can imagine that it would have real anti-aging effect.

Yeah. I mean, I think this is interesting 'cause we are looking like drugs affect a single target. They're a single molecule, a single receptor, a single target. You know, when you look at, you know, these longevity interventions, they have diverse effects across all these different systems. So a compound like urolithin A has many different effects across across the system.

That's an important point. And it goes back to this whole idea of what we talked about, geroscience. What does geroscience really mean when we talk about aging being at the root of everything?

Like geriatrics, like gerontology.

That's what I mean. Yeah, that's the—

The root of it.

Yeah, yeah, yeah.

But it's the root of it. That's what that means.

There's another example because these, you know, the way we practice medicine is based on a model that dates back to the 17th century when we discovered organs. You know, you go see a heart doctor, you go see a neurologist. There's a National Institutes of Health which has a National Heart, Blood, and Lung Institute.

The National Institute of Organs.

Exactly. So first, I mean, it's a national institute. It's not a National Institute of Health, a National Institute of Disease. And second, it's based on a 17th century model. Now, when we talk about urolithin A, it's not that it's going to help your immune system. It's going to help everything. Same thing, think about rapamycin, which is another darling from the longevity field. Now, its targets called TOR, target of rapamycin, is not only in the immune system, it's in your brain, it's in your muscle. So when you give rapamycin to someone, you're not affecting just the immune system, you're affecting pretty much the whole organism. And that's the shift that longevity medicine is doing from sort of organ-based reactive model to a sort of system-based proactive.

Yeah, you treat the system, not the symptoms or the diseases. That's, this is actually what functional medicine is. It's what we've been, I've been doing for 30 years and it actually works really amazing. Reasonably well, you don't, you really get to the root cause. Like you were talking about the root, not the branches and the leaves. And that's even the paradigm we use to describe what functional medicine is. We treat the root and the trunk, not the leaves and the branches. If you love that last video, you're going to love the next one. Check it out here.