Biohacking Your Heart: This Molecule Could Save Your Life

My view on longevity and cognitive performance is all about mitochondria. Fix the mitochondria, everything is better because.

They'Re foundational, irrespective of what cell or organ you repair the mitochondria, you can rejuvenate them. We have an army of amazing mitochondrial scientists, and they started looking at basically hearts of people who died of heart failure. You can sequence them out. And they saw so much mitochondrial damage in these hearts.

You think fatigue is normal. You think muscle loss is aging. You think low energy is your fault. It's not. It's your mitochondria. When your mitochondria collapse, your strength disappears, your mind slows, your future narrows. And for women, it hits even harder. New research shows that after menopause, mitochondrial decline accelerates. You lose muscle, your energy crashes, and you age from the inside out. But it's not a death sentence. It's just a setback, and it's reversible. Dr. Anurag Singh leads the world in fixing what breaks first yourself.

What we see in humans, if we really study that molecular level, the molecule induces mitophagy, so cleans out the faulty mitochondria. And in about a month, we start seeing what we call mitochondrial biogenesis.

His research uncovered a lost process, something we once triggered naturally. A way to clear broken mitochondria, A way to rebuild the energy at the cellular level, A way to slow aging at the source. He didn't invent it. Nature did. And now we can bring it back. A molecule born from the right foods, rare inside the human body and almost impossible to make naturally. But this isn't an bad, it's a roadmap. A way to rebuild your energy, your strength, your future. If you rejuvenate mitochondria, of course your heart is going to improve because it has the second highest mitochondrial density of anywhere in the body. The second place would be neurons in the brain. What is the average age of onset for mitochondrial decline in humans? To the best of our knowledge, energy cannot be created or destroyed, but it can be reclaimed. And today, you'll learn exactly how. You're listening to the human upgrade with Dave Athens Free. Normal doses too.

Normal dose gives you 500 milligrams of Myoper or uran. A better for not just muscle mitochondria, but for your inflammation and other things.

My view on longevity and cognitive performance is all about mitochondria.

Yeah.

And for 15 years now, it's been fix the mitochondria, everything is better because they're foundational. And the Reason I was so excited when your first papers came out. Like you've been secretly working in a lab for 10 years to figure out a compound that pretty much nobody makes enough of in their gut that radically rejuvenates them. And some mitochondrial stimulators, acetyl L, carnitine pqq. Widely available. You feel them right away. Yeah, but with timeline, most people don't feel it. It takes about two months. What happens after two months of getting the right dose of urolithin A?

So we've done a number of randomized placebo controlled trials over the last 10 plus years. The first trials we wanted to see. Now, what is clear is what you're saying. This is not a magic bill, that suddenly, you know, in a week or two weeks we'll start doing everything like you were saying with the other nutrients. What it does is it basically activates mitophagy, which is this, you know, cellular garbage removal process, and takes out the zombie mitochondria, out these damaged mitochondria that are just sitting there and clogging your cell's real estate. So it takes time to do that, to take the bad trash out and then to rejuvenate into healthy mitochondria. So that happens in about a month's time frame that you start hitting the biology in your mitochondrial rejuvenation. And that when we take biopsies or we take blood draws, we start seeing things like PGC 1 Alpha go up in the, in the mitochondria, which means now after the trash is rem, there's new healthy mitochondria coming. Two months in is when, if you actually go to a lab to test yourself out, like do a peak VO2 measurement, go on a, you know, oxygen consumption kind of a machine, that's when you'll pick up the difference.

Okay.

And to really feel the effects on, like, fatigue, energy or strength takes about.

Four months, about four months to feel it. Most people can't feel the slow ramp over four months.

Yeah.

And you might think, oh, it's I had more coffee this morning or something. But you can measure the results consistently. So we're all biased towards things you feel right away. And I know some brands that they'll intentionally include caffeine or the guarana extract, or just because they want people to be like, well, I took that, I really felt it. And then you have things like lion's mane, which is good for bdnf. A lot of the time you're not going to feel lion's mane because it doesn't work. And then you'll feel that one of them because it's properly extracted when it has heat and alcohol and all that. So feeling something right away doesn't mean it's working, but it's a good indicator. So I just want to let people know the studies are abundantly clear, the ones you've done, and it's not just one. And they're very well formulated studies showing your mitochondria are going to be happier. And I know that means you're going to at least have healthspan if that's your weakling goal. My goal is to have healthspan and extra longevity and you have to have mitochondria to do it. And four months is I'm going to call it, I guess you're saying at two months there's some meaningful benefit, but at four months you reach max benefit.

Yeah. Now we are doing longer even four months plus and we start seeing things like, you know, if you'd were to go to a doctor, get your annual blood work done, you'll see things like C reactive protein going down or all the inflammation markers going down. So we start seeing at a more whole body level bigger benefits beyond four months.

Okay. And by the way, if you're already saying, Dave, you've been taking this for five years, I want to take it to. Of course there's a discount for you. Timeline.com Dave, they give you 10% off. And well, that's part of how it works is I love supporting good research and sharing the news. What's the longest any one person has been on timeline?

I've been taking it for four plus years. But the oldest consumers, and I still remember them because when you're a research company doing research for 10 plus years, you go in the market with something nobody's ever heard of. They know you've done good research. But okay, what is your today the first hundred people, I know them by phone because I used to speak to them by phone. I would call them or they would write to me and these would, these are. The early adopters have stayed. And that's to me, you know, today we have hundreds of thousands of people taking the product, but they are this 10% critical mass that are believers. And a lot of time people say, oh, I didn't feel it after a month, I'm not gonna, I'm gonna stop the product. But what I do see is that actually, and this is fairly common in the supplement industry, if your supplement works, most healthy people won't feel it. But the moment they stop it. Yes, Moment they stop it, then they come back to me and say, hey, there was something happening when I was taking your product. I'm going to go back on it. And I think that's, to me, the success metric. If I can convert the folks who don't feel it to.

To the believers in my. She's my early 20s, my brain was cooked and I was really worried about it. So I bought $1200 worth of cognitive enhancing pharmaceuticals from Europe and things that especially back then, nobody knew about, like hydrogen and piracetam and selegiline and whatever. And I was so excited and took six weeks to get to my house. And I opened the brown paper bag and I take them all, and I show up at work and I'm like, nothing happened. This sucks. And I took them for a week and I was like, I wasted all this money and I quit taking them. And the next day I'm like, wait a minute. So I didn't notice that my brain could find words.

It was just.

It just was automatic. So when you feel more like yourself, it's invisible. But then when you lose yourself, you notice it. So you're saying when people take timeline. Yeah, whatever. But when you stop it, it's like the. The decline is faster. So you can see it. That's been my experience over and over. With supplements, you have to give them time to work.

Exactly.

Right. Unless it's something like modafinil, which is not really a supplement, but, you know, stuff's good. So this is my six timeline. What's my upper limit? I like these.

So we've gone two grams. So that would be eight of these gummies. There is no real upper limit. I mean, this is a natural molecule, evolutionary. Everybody made it. But we've just lost, you know, two things. We've lost our microbiome, and we have stopped giving the microbiome the good stuff.

Have you ever done a test of like 20 grams all at once while fasting or something like a bolus dose?

Not really, but why not? I know.

I want to be in that study.

Yeah. So like a high dose and then shift to a maintenance dose.

I mean, a loading dose works for creatine and things like that. It's not necessary, but it works.

That's an interesting idea. But what I do think what we need to do right now is combine it with things, other modalities like fasting or. We've already done trials. Now, starting earlier, we were doing trials with older adults who weren't moving much or overweight folks and the 40s. Now we've gone in the other extreme. We've done elite athletes, we've done soccer players, we've done weightlifters, we've done runners, middle distance runners. And they all don't automatically boost performance, but they all blunt the inflammation and their recovery is faster. So I do think there is an element to combine it with other interventions that we know work exercise, fasting, et cetera.

Is it better to take timeline at the beginning, middle or end of a fast?

From a scientist perspective, if I was doing a hypothesis, I would say beginning of a fast because fasting is already working optimally to induce autophagy. And this is just, you know, mitophagy is nothing but form of autophagy specific to the mitochondria. So that's probably when you'll get most bang for the buck. But we have done studies where we've given it with a big fatty meal or at the end of the day the kinetics don't change, so doesn't matter.

Doesn't matter for absorption, but it might matter for its presence during a fast. So you would say take it at the beginning of a fast?

Yeah.

Will timeline break a fast?

Not the pills. The powders have some natural pomegranate berry.

Not much though, but maybe, maybe.

And, and, and these are sugar free, so they won't either.

Okay. What does timeline do for mtor?

There's actually a number of groups who found that it does hit mtor, but I think it's one of those molecules that hits a lot of the key.

Longevity patterns explain what MTOR is in case people.

So MTOR is this mammalian target of rapamycin. That's the MTOR for, and that's how they found rapamycin, which was this old school drug that was also a natural compound discovered in some Easter Island, I believe discovered to be. And today, just so for your listeners, Rapamycin is sold as an immunosuppressive drug. But they found amazing benefits on longevity and that's mostly through MTOR inhibition that kind of regulates the nutrient sensing.

Although it seems to, it seems to have fallen out of favor because the dose of rapamycin that causes those benefits also causes like skin infections and some other things. Like there might be better ways to.

Handle the immunosuppressive aspect is what worries me a bit about rapamycin and something like mitopure. The new data we are seeing. Actually it's not an immunosuppressor, it's actually an immune modulator.

Does it Suppress MTOR though, even if it doesn't suppress immunity.

Not in immune cells. We've not seen it. They are. There are groups that have shown mild MTOR inhibition in muscle cells.

Okay. Not enough to matter though.

Not enough to matter. But I think it's one of those pathways. This molecule, as I mentioned, it's a modulator. So depending, for example, immune cells as we age, there are certain army of immune cells called the T cells. These are called the cytotoxic T cells that keep the infections away. They decline because there's an organ called the thymus that just disappears around 30 forties and you're left with just the bag of goodies that you were dealt with since the thymus went away. What we'd see actually is taking supplementation at the higher dose. There's a study we just did with the Buck Institute of Aging. These cells come back, they have better quality mitochondria. So I do believe this is different than rapamycin because it hits different targets and it's not exclusive to like rapamycin is for mtor.

If I was going to get another tattoo on this bicep, this one has trimethylxanthine, I might choose PGC1 Alpha. Talk to me about PGC1 Alpha. Why do I care? And what does timeline do to it?

What we see in our studies, and I'm again an evidence based person, so I can only talk about the data I have or we have seen.

Or hypothesis.

Yeah, or hypothesis. But if not unproven, then I will stay away from it. So what we'd see is if you take a cohort of sedentary folks in their 70s, don't move much, you take little chunks of tissue, muscle biopsies, and we look at how their health of their mitochondria is. They really look in poor shape. It's almost like they're crying for help. Okay. We give mitopure these folks, their damaged mitochondria clean out and then in about a month we start seeing increased PGC1alpha in the muscle cells in the mitochondria. So what PGC1alpha is actually, it's a sensor for the creation of new or healthy mitochondria process. We call biogenesis. So in about a month's time we see biogenesis.

There's two things that increase PGC1alpha reliably. One of them would be exercise, of course. Right?

Yeah.

The other one would be nicotine.

Yeah.

Right. So does that mean that maybe I should stack 1 milligram of nicotine with my 19th longevity gummy here.

You should definitely stack it with exercise is all I can say.

Well, why wouldn't you say nicotine?

Well, I'm not familiar actually with the data there, so. Oh my God, I'll have to study the data there.

To be honest, I will actually send you something. I had, I call him Dr. Nicotine on the show like 10 years ago. And I've been using very low dose nicotine for longevity and cognitive enhancement, like 35 milligrams because it's neuroprotective in the brain. And this is Vanderbilt University research showing a reversal of Alzheimer's disease and Parkinson's since 1986.

Oral nicotine, not like the patch, not smoking.

Well, actually the patch will work too, just not smoking. Smoking is bad for you. It's now starting to make the circles. Andrew Huberman just started talking about it and it's intriguing because of its effect on PGC1 Alpha in addition to the neuroprotection. So I'm thinking, all right, of course, exercise. But if you were to do timeline and exercise and maybe 1 to 3 milligrams, you know, half of a, of a little lozenge, you might get the Most increase in PGC1 Alpha. And so I'm assuming I want higher levels if I'm going to be exercising. So how do I get all the advantages? That would be how I would do it.

Okay, love to read that word.

Okay, I'll send it over. I know you're not recommending that, but since I'm an unlicensed biohacker, I can, I can make a hypothesis.

But wouldn't NAD also do that? Right. A lot of NAD molecules are touted to do PGC1alpha.

I didn't realize NAD raised PGC1alpha. If it does, you would want to do NAD or a precursor also. And you want to do that anyway for mitochondrial bioenergetics.

Exactly.

So that's a pretty powerful stack. All right, guys, next time you decide you're going to go into upgrade labs and do an AI workout, you can do that, or you could just go to the old fashioned gym, pick up rocks that have been concentrated into dumbbells the way cavemen do. And I respect either one. And you might as well have your PGC1 Alpha maxed, which means you lift less and get more benefits. And the stack we just talked about would be N.A.D. precursors. They're NAD plus. We just had an episode where they talk about increasing levels inside the cells a lot. So you could do qualia, you could do Timeline for sure, because you just have this crazy amounts of data for it. You could do 1-3mg of nicotine before the workout because you're gonna be like, yeah, it'll get you going. And then the final thing was exercise, just exercising itself. So that's four things that could be a really cool PGC 1 Alpha stack. And as a bonus on top of it, we could also do the tripling down on mtor. And I know timeline doesn't have strong effects on mtor, but you're going to be on it anyway. The way MTOR works is the more it's suppressed, the more it rebounds. Right. So the, the three things that suppress MTOR would be fasting, exercise and coffee. So your pre workout also is coffee and you do it at a fasted state and then you exercise and that's going to create maximum suppression. And then as soon as you finish. What raises MTOR nutritionally?

Well, nutritionally fasting, as you said, but what raises it? Oh, what giving?

Yeah, because we're suppressing it, then we want it to spike after we exercise. So what would spike mtor, I guess.

Would it be ketones? No, no, no.

Ketones don't affect mtor. Surprisingly it is. Everyone thinks it's animal protein because it has methionine. Sure. But it's not carbs. Carbs are way more increasing of mtor. So what you should do is after you're done working out or even halfway through, have a burger, get some carbs and get some animal protein. And that combination is going to spike it, but you're going to spike it in the context of being on timeline. So your mitochondria are really strong. When the mitochondria is strong, MTOR goes up. Tissue building.

Interesting.

That's a kind of a complex stack, but it's the tripling down MTOR. I've written about this, I've shared that over 10 years and that works mechanistically very well. And there's people say don't work out fast. No, you have to not be blown out adrenally to do this. But fixing your mitochondria with timeline ahead of time would be necessary for that.

And no MCTs, because mitochondria do like fat.

You can totally have MCTs or a ketone dial or any ketone donor. They're just not going to affect mtor. But they would make mitochondria happy. So we could add that to the stack. And because more energy when there's PGC1 Alpha and MTOR is Going to equal better results. So probably glucose and a ketone donor, like, might as well just go for it.

Why not?

You do that for one minute and you'll look like Hulk Hogan. Okay. Just kidding. But it's a good idea. One of the reasons I love having you on the show is that you have a really good picture in your mind of what's happening with these. And we had such a powerful conversation about GLP1 drugs and what they do to mitochondria and how would you use them safely. And the fact that, oh, mitochondrial support with GLP1s changes outcomes. That was really cool. And I've had a lot of people reach out about that episode and say thanks. Like it's not for or against GLP1 drugs. I think at low doses they're longevity drugs.

Exactly.

Especially when your mitochondria work.

Yeah.

Was this number nine of the. Of the timeline Gummies?

I.

These are really good.

Yeah.

I'm going to see if I can have so many that I feel it.

Maybe split them out. So you always keep your exposure high.

How would you spot a deceptive mitochondrial product on the market?

Big, bold claims with no data. You know, say it's clinically proven, but you can't find a single trial anywhere or a publication backing the data. That's one, let's say smoking signal red flag for me. Second, what we are seeing now and, and it's common practice, whether it's NAD supplements or others that are touted to boots mitochondrial health is you suddenly have this army of me too urolute and A supplements out there. And they'll say, oh, contains three grams, four grams. And you know, as a researcher who's researched it for 15 years, that's a, you know, the therapeutic window is around 500 to maybe around 1500,000, you know, in that range. And so when you go measure it, there's nothing. So that's how.

So. So they're making huge claims, they're selling it for cheap, and there's actually none in there.

Yeah. And the third I see very rampant is they'll say liposomal or enhanced bioavailability, et cetera, et cetera. And then when you actually go and try to see if there is any actual data that they have enhanced the bioavailability, there'll be very little evidence. So to me, those, at least as a researcher, I see three common red flags.

Got it. Assuming that a company is actually making liposomes, which are hard to make, so a lot of people say it's liposome. Well, no, you just mix it with phosphatidylcholine. So it wasn't really a liposome, but let's say that they actually do it. Do you need a study? Because anything inside a liposome will enter the body better than not being inside liposome.

So you don't necessarily need a study because you already know that you will get better exposure.

It's like saying IVs are better than oral.

Yeah. But you do need the study to know that. Well, for URL tonight, maybe not. Because. Yep, there is really no upper limit, but there are molecules where more absorption could have a safety impact. So that's one of the reasons why you would need a study.

There is a dose response curve for all kinds of things. Right. And so sometimes you. If you have a really fast spike of it, you have totally different effects than if it slowly ramps. And for a lot of things we don't even know. Right. And since it would be physiologically impossible to get whatever a substance is like that. And I think there's. There's definitely some caution warranted for liposomal formulations. Just like, I wouldn't take a lot of the things on the shelf, you know, mix them in some sterile saline and inject them either even through a filter to get like. Because nobody knows what that does. One of the things that's new in the world of urolithin A is that you've got some cardiologists calling you. What's going on with cardiology and timeline.

So we just published a new paper, fascinating new study in the journal called Eye Science. And what it we show there is actually for many years. We know that the three cells that have the highest abundance of mitochondria are the brain, the neurons, the skeletal muscle, and the cardiac muscles. Kidney is another one. But we haven't really focused on cardiac aging because we were so focused. You know, research, again I always say, at your show, is two words. Reinsert. So as a company, you start somewhere, spend 10 years studying muscle, now you're studying immune and skin. And what got us into cardiac was a lot of folks told us their VO2 was improving. So of course, VO2 is about mitochondria, but it's also cardiovascular. And then we have an army of amazing mitochondrial scientists, and they started looking at basically hearts of people who had died of heart failure. These are, you know, you can sequence them out. And they saw so much mitochondrial damage in these hearts. And so then we went, of course, a step backwards into animal models of cardiac aging and heart Failure models. And we tried to see if we could rescue some of these features of cardiac aging or heart failure with by giving mitopure supplementation. And we were able to see about a 20% reversal of protective effect of mitopure. Wow. And so 20%.

So you're saying if someone's having a heart attack, do they, do they take it right then or they have to be on it ahead of time?

I mean, there are thing measures like ejection fraction, so you can measure how the contractility and the blood volume coming in into the heart is, which is kind of an idea to give you how good your heart function is. And so that's one thing we can measure.

How quickly does timeline change someone's ejection fraction?

So we haven't done a randomized trial yet. The data I'm telling you about is in animal models, okay. So in animals, in about eight weeks, so two months.

And. And if you've read my longevity book or my exercise books, I talk about ejection fraction. And if you don't remember that part of it, that's okay because it actually sounds kind of like the other kind of edge word that I'm not going to say. So what this is, is in healthy young animals or humans, one heartbeat can sling a huge amount of blood through just one pump. But if you do a lot of excessive cardio or you have aging, one pump, even under stress conditions, only does a little split. So you can like cheat. You can cheat and like train the heart to, instead of moving blood volume, if you do a lot of cardio, you actually train it to go blip, blip, blip. So you have a higher heart rate, but less blood going through. And if you want to live a long time and be powerful and have stress resilience, higher ejection fraction equals longevity and power.

You got it.

Well said.

Absolutely perfect.

And you're finding that eight weeks of taking timeline increases ejection fraction in animals?

Yes.

Okay. But not yet in humans.

So these are studies that we will do. Now what we do have is we have tons and tons of other randomized trials we've done, and we have plasma and blood from these volunteers. So we can go and look at the effects on markers of cardiac damage, for example. And one of the category of biomarkers that is coming up, Mayo Clinic, has put the spotlight on them. These are called ceramides.

Nobody talks about these.

These are essentially mitochondrial toxins. The higher more damage to the heart you have, the more clogged the arteries are. Likelihood is you'll have more ceramides floating around. And what we do see now is that in all these studies we can blunt the levels of these plasma levels of ceramides and older adults and middle aged adults.

I have a confession to make. I've always been confused by ceramides and I've known about these for 20 years. And on one hand I know that if my body's producing more ceramides, that's a bad thing because it means I have mitochondrial damage. I also know there's really good studies that say if you smear ceramides all over your skin, that it rejuvenates your skin. But I also know that if I put things on my skin, it goes into the body. So are ceramides causing damage or are they a signal of damage that causes healing?

So there's a certain different classes of ceramides. So the middle and the long chain ceramides that accumulate in the body are not so good. That's the one we are seeing getting blunted. The ones that we smear on our skins and probably take are plant based ceramides. So these are extracted from things like wheat and rice. And so they're, they're not very similar.

To the, they don't bioaccumulate.

Yeah.

And they cause tissue.

Yeah. So they're the good ceramides.

Got it. Okay. Good ceramides, bad ceramides. Sounds like a book. Thank you for clearing that up, by the way. No one's been able to answer that. What is the average age of onset for mitochondrial decline in humans? To the best of our knowledge.

So mitochondrial decline is always happening, so.

Oh, even birth. Got it.

Well, not when you're two years old and running around like crazy, you know, and you're full of energy. So what happens in and every cell is that the real estate is when we are young is full of healthy mitochondria. That's giving you a lot of energy. And there's like a yin and yang, it's like a balance Right. Between healthy and damaged mitochondria. The decline takes a drastic shift towards more accumulation of the bad ones starting in our late 30s, 40s. So I would say around early 40s is when there's slight uptick into the decline of mitochondrial capacity. And you can say, well, that's the free radicals that are starting to cause a damage or it's the accumulation of the zombie cells or inefficiency of the mitochondrion itself. And then it accelerates really towards the 6, 7 decade of life around the 60 year age mark. So that's what we know. And when we pull biopsies or blood from 60, 70 year olds, if they're not eating right and they're not moving right, it's a scary sight to see. And now we have, we're probably one of the few groups that is now using electron microscopy to go at a deep level. Now if you go look at a 60, 70 year old's mitochondria inside a cell, they all look circular. So it's almost like circularity is a bad thing. And they become like grumpy old people, they don't talk to each other so they become fragmented, they separate. In a young person, if you look at with the electron microscopy, they're all like tubular and they're rod shaped. Yeah, they're rod shaped and they're all in a closed network. It's almost like in a whole grid of energy.

It's kind of like young people should be shaped relatively like rods. And as you get older, you become rounder.

Yeah, it's exactly like that as above, so below this. But what we do see is that irrespective of what cell or organization you repair the mitochondria, that you can rejuvenate them and start to look back like they should.

I know that you have a bunch of new data underway for cardiovascular and there's a bunch of things that you can't say because, well, you're a researcher and because you're involved with timeline. But I can say these things as someone who has written a major New York Times science best selling book on mitochondrial function and the brain. If you rejuvenate mitochondria, of course your heart is going to improve because it has the second highest mitochondrial density of anywhere in the body. And in men it's the top mitochondrial density. The second place would be neurons in the brain. So it stands to follow. And I would bet, and I am betting with my behaviors that taking timeline is also going to be protective of Alzheimer's and Parkinson's because anything that increases mitochondrial survival or, or turnover and getting rid of the bad ones because of how it works, it's going to help your brain feel better now and not age the same way. So this is why I'm using it. What I want to know now is have you done any animal studies on brains and Alzheimer's and Parkinson's or am I just going out on a limb? I don't care. It's a limb, I'm taking it. And I can tell you why. I can tell you the mechanisms. PGC1, Alpha, the whole thing. But what do we know?

We know, and this is not our research. So as I said, we have focus laser focused on muscle, immune, skin. This is research coming out from three of the top labs in the world that study mitochondria and longevity. This is the Buck Institute, the National Institute of Aging and another group in Europe. What they find is that when they screen libraries of whether repurposed drugs, natural compounds, and they also look what are the two pathways that are going down the most in the brains of people who have Alzheimer's or mild cognitive impairment, et cetera, Dysregulation of mitophagy is the number one and inflammation in the brain is number two. Boom. And. And there's a group in Harvard, actually that came to me and said, we want to do a trial because we did the screen of 4,000 compounds. And the top one that hit, because it's safe and it hits these two pathways. Is your Lin A.

The very top out of 4,000?

Yeah. All these three groups found the same thing.

Are you feeling pretty good about the last 15 years of research you've done?

Again, if you look at how molecules are discovered, how Omega 3 was discovered, it was discovered about 25 years back. The original researchers, nobody knows it. Yeah, probably now. Right. Everybody has taken it and gone in like 20 other aspects. As a researcher, that's what you aspire to, that you see the new idea into somebody. And so that's what's happening. And now these people are coming to me because they know how to. That we know how to run clinical studies. And they want to do Parkinson's disease, they want to do a trial in sleep disorders. But there's a group that is studying people in their 50s with sleep disorders. All of them turn into Alzheimer's 20 years down. And so they think that this metabolic impairment early on, if you can reverse with things like URL DNA, you probably have a better chance than when it's too late to tackle.

When I went really deep on sleep because I was a five minutes of deep and five minutes of REM per night kind of guy, go to bed at 2am in my 20s and I couldn't go to bed earlier because of circadian stuff. And I fixed all that last night. I slept six hours and six minutes, but I got an hour and 20 minutes or so of deep and REM. Not bad. Probably should have slept another half hour, but whatever, right? Like, so I've completely fixed it. But I've been on timeline for many years now, ever since you guys first launched and all the other stuff that I do. But having studied sleep very deeply, I found two studies showing that the glymphatic system, which is the. The waste pump, where all the cells in your brain dump their cellular fluid, their water, because it's got toxins in it, toxic proteins, they dump them, and then you wash it out with cerebral spinal fluid. That pump, I was like, it has to be driven by mitochondria. But I can't prove it until I found two studies that says it is. A dysfunction of your glymphatic system causes Alzheimer's. It's not the only cause, but it's a major contributor. So timeline fixes mitochondria, fixes glymphatics, equals less likelihood. I will predict that. In fact, I'll make a bet on that by taking timeline because it helps on other stuff. Anyway, bonus thing there that you might not have heard about because it's unusual. It's one of my books. Raising the height of the head of your bed by 6 inches so it's at a slight angle, has a profound effect on drainage of cerebral spinal fluid from the brain and probably reduces Alzheimer's. It's kind of a cool thing. So do that and take timeline. Why not?

Fascinating.

Yeah. And yes, there was a study on that. Okay, it wasn't a study on Alzheimer's because that takes a long time, but it was a study on the glymphatic drainage and cerebral spinal fluid dynamics. By the way, guys, it's timeline.com Dave, and they'll give you a discount. And I'm not kidding that I've been taking this since it first came out. The research is incredibly powerful, and this is the guy who led the research. So, you know, you got to take it at face value. If one of the benefits the study shows is true, and it is, then it's worth it. And all this other stuff, it like, I'm only going to take so many pills. It's a big number, Right. And I'm only going to do so many things every day, and I'm only going to spend so much money on something because this is mitochondrial and very focused. If you can affect the mitochondria, you get the most benefits in all the different branches of mitochondrial dysfunction, which, let's see, what are the four killers from superhuman. It's cardiovascular disease. Oh, mitochondria, diabetes. Oh, mitochondria. Let's see, Alzheimer's. Oh, mitochondria. Oh, cancer. Oh, mitochondria. So if all of those are mitochondrial disorders, And I do anything, including CoQ10, anything that helps my mitochondria, my risk of dying from something stupid goes down. So this is very, very high in my list of things that I take every day. And if I was going to cut my supplements by 80%, timeline would still be on my list of things I take. And that's because of the strength of your research. So thank you for figuring it out.

The other thing common to all those super killers that you mentioned is inflammation.

Isn't inflammation almost like the smoke signal of mitochondrial dysfunction?

It is, but you would think it's obvious. But you know, having been in this field 20 years, I was trained as an immunologist and then I moved to mitochondria. Scientists work in silos. So if you're studying immune cells, you could pretty much spend 40 years studying immune cells and don't think about mitochondria and it's vice versa. Only now there is a link that inflammation triggers damage of the mitochondria or vice versa. The damaged mitochondria become leaky, the damaged mitochondrial DNA leaks into the circulation and is an activator of the immune system. So it's almost like a circuit. So this is new research still in early days coming out, I've come across some of this.

It is really fascinating because, you know, mitochondria get stressed. You get something like a voltage gated calcium channel from EMF or something. So the mitochondria puffs up with calcium and explodes. It releases its DNA, which is a signal, but it also releases ATP into circulation. What does ATP circulating not inside a mitochondria do to the body?

Good question. It's not something I'm too familiar with, but I would argue it's not as beneficial. It's probably kind of like a smokescreen for, for the other organs.

It's really interesting. I have used over the past 20 years multiple times straight ATP from plant sources. Or I think it was from adrenochrome. I'm kidding. I don't know if you've heard of that. So by the way, a whole bunch of people like what? I knew Dave was in a whatever because adrenochrome is something I've never tried, but you can buy it for 300 a vial. It's just oxidized adrenaline and it's easily available. So I don't know about all that weird conspiracy stuff, but it was funny. So there you go, ATP. I don't think it could be from humans, so it's got to be from some kind of Cell culture to look at where they got it. And I've seen sprays, I've seen capsules, and you actually feel a bit of a rush from it. So some of it is taken into cells, but it does serve as a signaling molecule of mitochondrial damage. Now, that could be a good thing or a bad thing.

Yeah.

And I don't. I don't take this stuff regularly, but I think it's a good thing in that case because it could cause mitochondria to, like, man up and get stronger or it could cause them to go down inflammatory pathways. We know their DNA causes inflammation. I think ATP as an extracellular signal is there and there are papers on it. I just don't remember all the results.

Interesting. Well, I know there's a lot of mitochondrial transplantation coming in also where they purify mitochondria and then they inject what they think are good quality mitochondria, which presumably are putting ATP.

I want to try a mitochondrial transplant. It's been on my fantasy list since then. I think my mitochondria are little bastards. Right. I want some, like, really superhuman ones that are highly resilient to all the stuff that mine aren't. And that sounds kind of cool, but it could change the nature of your consciousness, which is the downside of that.

Yeah, true. Yeah.

So do you think mitochondria are related to consciousness evolutionary?

These were bacteria. They integrated with the host into their. They have their own DNA. They obviously keep us. Every time we get off of a chair, we have a thought. So I would say probably there is a chance they have a. You know when you get brain fog and you're not thinking clearly, it's all mitochondria.

I kind of feel like they're the puppet masters and the host is actually just their petri dish.

Possible. Yeah. Yeah. They're controlling us. We think they're. We are controlling them.

Yeah. My newest book that's just coming out about us, we're recording this. I make a pretty good case for that. And one thing I do know, for professional athletes, increase mitochondria increase performance. But when you're dealing with meditators and shamans and energy workers and all that kind of woo stuff, all of them increase mitochondrial function and they're like, wow, those really aren't the droids you're looking for. You know, they, they, they experience. And I experience the same thing. My ability to do neurofeedback, to end or altered states goes through the roof when I do anything that enhances mitochondrial function. So I have a whole stack that we use at 40 years of Zen to get people's mitochondria there. And my data is that people can do these advanced meditation practices for two and a half times longer with mitochondrial stimulation. Because there's the point of, you know, meditating with intention where you just hit a wall. Like, I can't do it anymore, but we move the wall way out.

Fascinating.

So maybe what I ought to do, in fact, I'll work with the team on this. I will suggest to people who come to 40 years, then that they should be on timeline at least two months before they go in. Because, like, if you're going to spend almost $20,000 and five days with a team of neuroscientists upgrading your brain, maybe your mitochondria should be all the way on. So, all right, we're going to add this to our stack. I just thought of that.

I mean, things like red light, things like sauna, they all have these profound effects on mitochondrial health. Right? I mean, so I think it's a constellation of things you can do.

Acyl carnitine. What is it? Why do we care?

So it's another nutrient. So there are different ways you can improve mitochondrial health. Urolithin A mitopure is just one way to do that through. As we talked about clearing the bad, damaged zombie mitochondria, acyl carnitine makes the mitochondria, the healthy ones, more efficient, so they're more efficient at producing. So there's a pathway like fission and fusion involved with how mitochondria talk to each other and how they produce energy. So mitochondria are like a factory. It's almost like an assembly. And, you know, I'm getting a bit nerdy, but there's different complexes that, you know, work almost like, like a motor. And that's where two molecules are very key. Acyl carnitine and CoQ10, because they're integral to the machinery. And so a lot of times, people take statins, for example. The statins deplete this machinery with CoQ tenins, a lot of people have CoQ 10 deficiency after statins. So a lot of drugs are known to kind of have an impact on these kind of molecules.

I mean, statins break the mitochondrial membrane, which is where electricity gets generated cells. Yeah, seems like a bad idea if you're into longevity. But hey, you know, you could always ask Peter Atia. He still likes them. But the standard stack, whether you're on these things or not, if you go back even to the 90s for longevity. It's always Coq 10. And I've been on between 100 and 300 milligrams of that stuff a day most days since I learned this.

Yeah.

And 500 milligrams of acetyl L carnitine. Right. And you do that to improve fatty acid oxidation in your mitochondria. And doing that over the course of time is profound. And now you have the membranes working and you add timeline in. And now timeline is increasing. Mitophagy and increasing. Is it number of mitochondria or just power of mitochondria or both?

I think it's really the energetics, the. But you can stack up the NAD boosters on top and that will even.

Ramp up even more.

Even more.

Wow.

And we didn't talk creatine, which is also, you know, becomes phosphocreating, which is the building block of ATP. So I think that's the perfect stack.

It is the perfect stack. In fact, I'll put that in the show notes for you guys if you're rapidly taking notes on that. Let's talk about creatine for a little while. Creatine's having a moment right now. It's been used in longevity circles for mitochondrial purposes for a long time, but we always believe like 3 to 5 grams a day is what you should do because, you know, you could go bald, you could have kidney dysfunction or some other thing. But lately people are talking about 10, 20 grams a day. What's your experience? What do we know?

So personal experience. I love creatine. I think it's one of this supplements that I feel in effect.

Yeah.

Outside mitopurin, maybe magnesium, I would say. So I take 5 grams and I haven't. I've read the literature where people do a, you know, like a bolus dose, 10, 20, and then go to 3 or 5 as a maintenance dose.

It's like the old school bodybuilder.

That's the Bro Jim, Bro crowd kind of. But I think the longevity space, it's in that range of 5 grams. But a lot of people are concerned. Like my wife takes it and she's always worried about water retention, probably that I've told her it's just a met. Yeah.

You will get water retention in your bicep where you wanted it, but you're not going to get it, you know, under your skin. I've seen a lot of people doing 10 to 20 grams a day, and I feel very comfortable if I got crap sleep doing that. In fact, there's One study out there that shows taking a huge dose of creatine, like 20 grams after a night of really bad sleep causes cognitive performance to be better than if you just got a regular night's sleep. So it can fully restore and even then amplify your cognitive function. You should still sleep. But there are some issues with higher doses of creatine that people don't oftentimes talk about. I think the hair loss thing is probably a myth, but creatine can cause your body to need more of unusual forms of folate. And it's not methyl folate, the 5 mthfr kind of thing that we've, you guys have heard about on the show. It's the kind that you would get from eating romaine lettuce. And it's the kind that I recommended in my first book on fertility, my very first book, folinic acid. And so if you take creatine and like, I'm too wired, you're probably deficient in folinic acid, which is just available as a supplement.

Oh.

And it's being used to treat autism these days. Like my book was like, how to have a kid without autism. Like, you should take folinic, not folate, but folinic acid if you're pregnant or plan to get pregnant. But the other thing, and this is where they don't tell you this, they'll say, oh, take creatine. So I went, I had surgery a couple months ago and I'm like, I'm gonna heal fast. So I'm eating three pounds of beef a day. Amazing. Just to get the extra protein in. And I took a ton of creatine on top of that, 3 pounds of beef, 10 grams of creatine in there, I took another 10, 20 grams. And I'm waking up at 3:30 in the morning, absolutely raring to go. Right. Like, what is going on? Like, I have so much energy. This is really good. Increasing ATP to a certain point reduces sleep drive. So normally if you wake up to pee at 3:30 or 4:30, then you would just go back to sleep. But if you wake up, you're like, I'm done. Even if you wanted to sleep more, I've never experienced that in my life. And high doses of creatine do that for me.

I, I think I've heard also same thing for people, bump up the dose of urolithin A.

Beyond that, their sleep drive goes down.

Not that sleep drive goes down, but the fact, well, it could be that or, or it, I mean, my 14th coming, they wake up like an automatic clock switch right at 4, 4:30 and they feel like they're ready to go. And it's not like that slow slumber waking up. It's like, okay, I'm ready, let's do it. And they don't feel fatigued during the day. So I think you were mentioning about jet lag as I we started the show, I, I think that's another area where I haven't seen nutrition and supplements crack the space really. And I think mitochondria can actually, and I do believe that's where creating and things like mitopure could, could play be a game changer.

I don't get jet lag anywhere on the planet. And I use the truedark glasses, the darker ones that are designed to tell my brain it's night no matter what's happening outside. And I use meal timing. Don't eat when it's dark where you're landing. And then I always use super high dose electrolytes that contain sodium in addition to other things. I put extra salt on my food. I take adrenal support, like adrenal glandulars just to help the cortisol system adjust. And I take a bunch of extra creatine. And I'm always taking timeline, but I never thought of just adding even more. But it seems like it might be a good idea.

I think if you do 5 grams of creatine instead of that high dose you're talking about and switch the deficit with something like timeline, it could work.

It totally could work. By the way, I take three grams of creatine now and I do it only in the morning because if I do more than that. Brent, I eat a lot of beef too, so I get it that way. If I do more than that, I'm too stimulated. Part of me says this is great. In my entire life, I was always the guy who I don't want to wake up before 8 o'. Clock. I'm so tired. And then I'd stumble into work and I literally have six podcasts today. And I woke up at 4:30 and I've done my cold plunge and my sauna and my neurofeedback and like a bunch of other stuff, right? And I'm just, I'm just so like happy. And I go to bed early though. And that's maybe one of the things that happens if you fix your mitochondria is you start going to bed earlier just because like you get tired because they're now connected to the environment better.

I don't know.

Is There anywhere on the planet where I could get a urolithin A intravenous dose?

Not yet.

Why not?

I know it's catchy in the NAD field where everybody's going for a IV nad shot. The thing with urolithin A, it likes fats to dissolve. So there's a bit of a technological where you would have to develop a formulation specific, blend it with phosphatidylcholine because.

I get that stuff in IVs anyway for. For fixing my mitochondrial lipids. Right. Like either PS or PC would be life changing. Sign me up for that trial. Okay.

Yeah. And second, we will have to take a look at the regulation a little bit.

First book ever I wrote because the mother of my children was infertile and my daughter just turned 18. Happy birthday, Anna. And we wouldn't have had those kids if I hadn't done five years of intense research that resulted in that first book. And we restored her fertility without IVF and all that stuff with a mitochondrial and hormone and toxin centric view on reality. And you guys can read the book to this day. It's called the Better Baby Book. I'm not trying to get you to read it, but it works. So that book convinced me. I'm not worried about the population problem. I'm worried about the fertility problem because it was already crappy back then and it has plummeted ever since. And the autism rates have gone through the roof. And thank goodness Bobby Kennedy's working on that problem. It's mitochondrial. It's always mitochondrial in my part of the world. What do we know about mitochondria, timeline and fertility in men or women?

So early, early days, early research. Two groups, one in Brazil, one in Portugal. They've. One has been working on male infertility, one has been working on female infertility. What they do see in male infertility is in the sperm. Most of the mitochondria are around its neck. You know that they are the motors that allow sperms to swim faster.

Yeah. It can't be a swimmer without mitochondria.

Yeah. And so what they're seeing in this early research is not randomized clinical trials, but, you know, culturing infertile sperms with different doses of eroltin a might appear. And what they'd see is that the motility of the sperms gets better. And in ovarian aging or in female infertility, there's two groups, actually, one also in Colombia and Princeton where they're showing that ovarian aging is very closely Tied to mitophagy defects and mitochondrial dysfunction. And in species, cells, animal models, they can reverse it partially with urolithin A. We have just started taking early steps in defining where's the right groups who can do a proper randomized placebo controlled trial on that area.

The cool thing is, as a biohacker, I'm always willing to say, well, what's the risk and what's the likely benefit? Given a hypothesis, that's a likely hypothesis, and if the risks are other benefits, which is what appears to be the case with timeline, there aren't like contraindications for it that you found, are there?

No, I mean, again, it's very safe. It's a molecule, as I said, evolutionary, all our ancestors made and we've lost it. At least I have lost it because I took a bunch of antibiotics early on.

There's a little known fact about women that I think explains so much of reality. We talk about mitochondrial density like, oh, it's the highest in the brain, in the heart, it's actually not true. There's 15,000 mitochondria in the average neuron, in the average cardiac cell, in the reproductive system, in women, in the ovaries, there's a hundred thousand mitochondria per cell. So I think this is why female intuition happens, because as far as I can tell, mitochondria are of direct connection to life around us in a way that we don't really perceive. Maybe that's too mystical for people, but it seems to be the case whether I'm right or wrong about that and female intuition, it is a source of power in women. And it would make so much sense that the ovaries are using mitochondria to sense the world around them, to figure out which of these billion eggs should I choose to have come out two months from now. So they need a lot of processing density, almost like a little brain to just figure out what is the most likely, what is the most special ache. Well, increased mitochondrial function, increase ovarian function, and it just makes so much sense on every level. I understand about biohacking biology, longevity. So if you want to have babies or just have a healthy reproductive hormone system, focus on mitochondria. Everything we've talked about in here, whether it's NAD, CoQ10, creatine, timeline, like that's the stack. And here's the hypothesis. If your mitochondria are working better three months before you get pregnant or longer because you got rid of toxins and all this stuff, your body will do a Better job of picking the right egg. And the survival rate of your child will be through the roof. And the chances of birth defects goes down. It's not gonna be eliminated. The chances just go down. Anything that was mitochondrial in origin, you can get rid of that. So no, we don't have studies for everything I just said. It's just how stuff works in my view of the world. So I, I think you have an obligation to take care of your mitochondria if you're looking to have kids, because it'll be hard to have them anyway without it. And if you do, you'll have to have healthier kids. Shoot holes in what I just said.

I cannot because I 200 agree with what you just said. But I again, as a.

There aren't studies. There have to be studies.

Yeah. So I, I have to wait to see the studies. And we are hot on it. So we are, we are running and planning to run these studies also. Third area is also in vitro fertilization, where I do think it could have a, you know, where you can actually turbocharge and give yourself a higher chance of fertilization.

Do. Do eggs, they must have mitochondria in them. Right? But maybe not as many as sperm. On a, at least on a density basis, the egg is much bigger than the, than the sperm. Like the percentage of weight of mitochondria and sperm is higher than eggs. But having healthier mitochondria in the egg is going to help the egg do a better, a better job of sensing and choosing the right sperm to enter. Although an ivf, I guess it doesn't get a choice.

Yeah.

Okay.

Yeah. And most of the mitochondria you inherit are from immaternal anyway.

Of course. Yeah. They have to be in the egg. The instructions are in fact, when the, the sperm drops its tail on entering, it drops most of its just to get to there.

That's what it needs the mitochondria for.

It's a, it's a fascinating world.

And so we talk about consciousness and we talk about evolution of life. All mitochondria.

It really is. I, many years ago, the founder of the American Pre and Perinatal Psychology Association. When I first got into personal development work, she just like spots me in the room, was like, you tell me about your birth. And I'm like, hospitals, vaginas. Like, what are we talking about here? She just recognized that I had birth trauma. I was born with a cord wrapped around my neck and I was like carrying it and just this reactive sympathetic dominant pattern and she was very wise. So she had me do this birth regression with her. It was a 10 day personal development thing, completely outside my comfort zone. In fact, it kind of freaked me out, changed my view of reality. And I remembered like sensations and visions that made no sense to me and I kind of put them to the side, reprocessed the birth trauma. I was actually a much happier person after I did that. But 10 years later I read a book, a pretty unusual book that talks about the. It's a shamanic kind of thing, like the felt states of embryonic development. And apparently people from different meditation lineages have the ability, and I know it's real because it happened to me, and to go back and remember the physiological sensations of each step of birth up to and including the moment of conception. When I came across that body of work, it's called subcellular psychobiology is the name of that field. They described exactly what I had seen 10 years before doing my first birth regression. And I was like, oh my God, maybe we do remember what's going on in there. And some of the healing states that people go into at 40 years of Zen are around like what the experience of the cells or the body, whatever you want to call it, inside the womb at different stages of gestation. So I kind of look at that whole thing as a sacred space. And you better have good mitochondria to take full advantage of it.

It.

Right. So for what that's worth, it's, it's, it was this pretty mystical stuff, but man really threw me for a loop when like I saw some kind of random visions when I'm regressing and then all of a sudden have someone else explain exactly what I saw. And it's that moment of the tail dropping. I'm like, oh my gosh, who would have thought?

Fascinating.

Is there any new information about skin? Because I've been using timeline. And just to be clear, guys, it's not the only thing I use on my skin, but I do use it on my skin every day. I use a bunch of different things from companies that come through. Any new data on skin, mitochondria and timeline.

We have a lot of new data coming out. So to rewind, skin cells also have mitochondria. They also go down in their energetic capacity, AKA poor mitochondrial health as we age. They also skin being the organ that has a lot of environmental toxins to adjust to. So it's like a double whammy. And what we see in our studies is mitopure containing topical products or cosmetics as we say them, they can reverse a lot of this dual damage. So the inflammation and the mitochondrial damage. Now what we have done, what probably nobody else does, is we actually have tested each and individual product. Now we have a range of them. We have a day cream, we have a night cream, and now we have a new eye cream. Because eye is the area where most people first see these signs of aging. And they all do an amazing job at a cellular level hitting on these MMPs. We talked about it last time. These matrix metalloproteinases that degrade collagen, cause your wrinkles around your eye area and they just keep your skin better hydrated just because now you have better cellular health and skin health. So that's the new data we have. We are now taking skin biopsies, and I was telling you we're doing electron microscopy to actually see if we have rewired the mitochondria in the skin and at what level? Is it the dermis, is it the epidermis? So that's where we are headed.

We should talk again in about six months because the rate of knowledge about mitochondria aging, urolithin A and all the research you're doing, it's changing so rapidly and it's more and more impressive each time. So I want to hear the result of that on the skin. And certainly I'm doing it preemptively. And I did take, I don't know, 18 or so of these gummies. And we'll say I'm exceptionally good at detecting my state. Just six months of neurofeedback and all the heart rate variability, all the stuff I've done, I'm feeling something and it's not that subtle. The sensation is a lot more.