Pod Insights All-In with Chamath, Jason, Sacks & Friedberg Bryan Johnson: I Just Took the Most Powerful Dose of DMT in the World... Here's What It Was Like About this episode (0:00) David Friedberg intros Bryan Johnson
(0:54) Why Bryan Johnson did 5-MeO-DMT
(12:56) What brain scans actually show
(18:36) Psychosis, bad trips, and life-altering decisions
(26:23) The next frontier: organoids and gene therapy
(33:26) GLP-1s, abundance, and human optimization
(35:35) The longevity drug nobody's talking about?
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Transcript Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:00 David Friedberg? Brian Johnson, thanks for being here.
0:01 Speaker 01 Yeah, it's good to see you.
0:02 David Friedberg? How are you feeling? Maybe just share with us what you did a few days ago.
0:05 Speaker 01 Yeah, I did a, I did five MEO DMT, which is the most powerful psychedelic on the planet. Somewhere between five and 10 times more powerful than DMT. And so, yeah, it's, so it's been 48 hours. I'm still learning how to talk about it.
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0:54 David Friedberg? Before we get into your experience, why did you choose to do it?
0:58 Speaker 01 Two things. One, mostly as a longevity experiment. So when we, when I started this project five years ago, the, the approach we had was go through all the scientific evidence ever published on health and longevity. Try to find the interventions that have the best evidence. And for effect size, and we just went down the list from top performing on down. So of course, you start with exercise, nutrition, you know, sleep. And you work your way down to things like hyperbaric oxygen therapy and sauna, and then rapamycin metformin. And so we never actually had on our radar psychedelics. They were always either an ancient medicine, you know, being used in ritualistic practices, or being pointed at things like depression and anxiety in certain trials.
1:42 Speaker 01 But it was never understood as a rejuvenation protocol, something that was for anti-aging. And so we found a preclinical evidence in mice on psilocybin. We thought, that's interesting. And so we did the world's most studied, the most quantified experiment doing psilocybin, three doses at 25mg of psilocybin.
2:00 David Friedberg? Which are pretty high doses.
2:01 Speaker 01 Yeah, it's a clinical dose, a very, very close to a hero dose. And we found that we think it's a longevity therapy.
2:08 David Friedberg? Let's get to that data in a minute. But then you decided to try five MEO this weekend.
2:13 Speaker 01 Yes.
2:14 David Friedberg? Walk me through the experience, because you televised the whole thing. It was livestreamed. You looked amazingly calm going into it and going through the process. Walk us through your experience.
2:26 Speaker 01 Yeah, I think those who have done five MEO would probably relate with me that it feels like an impossible task to explain what it's like. So that caveat said, I'll give it a go. I'm stunned, absolutely floored, speechless. You, you basically experience raw consciousness and raw intelligence. It's this, so whatever, when I say these words, take these words that I commit to you, take that idea, multiply it by a thousand, and then move out infinite depth, infinite width, or width and depth, and then dimensions. And like, that gives you kind of like
3:08 Speaker 01 a rough map of like, the size and space that you deal with. And it was incredibly hard, because you, you get blasted into this space that is so foreign, you don't even know what's happening. It happens very quickly. Like, you inhale it. I did nine milligrams of intramuscular, and then seventeen, eighteen of it vaporized, and it hits you within ten seconds. You're just, you're out. And so, but what happens is you, you get in that space, and then Visual changes. Very, very little visual. Like, you see, on DMT, it's very visual, you'll meet the, you know, like the elves, or whatever else. This is not a visual experience. But you, you
3:51 Speaker 01 get in this world, and you lock in to basically, you either panic, because you feel like the gates of hell are going to open, that the, the stream of existence is just gonna just tear you to shreds, it's gonna shard you. And if you give up Like, break your brain. Yeah, if you feel like it's gonna like, threaten your sanity, like, is it gonna chop you up into little pieces? And so in that moment, you have to say, do I try to wrestle this, and I, I need to just like, wait it out until it's over, or you just relent, you say yes. And you have to, in that moment, you have to say yes, so thoroughly. You have to
4:32 Speaker 01 release all attachment, all preconditions, all want, all desire, you have to release self, ego, control, you just have to just relent entirely. And then when you do that,
4:46 Speaker 01 It opened up this unimaginable bliss and euphoria. And I, again, this is like a V1 of trying to explain this, but if I list out the, the most
5:01 Speaker 01 dynamic experiences I've had of a human, you know, uh, like certain accomplishments or getting married or having a child or overcoming a difficulty or like, you know, state your list of things. This is without question the most dynamic experience I've ever experienced as a human.
5:19 David Friedberg? Does the internal chatter, the internal monologue of the ego turn off?
5:24 Speaker 01 Does.
5:24 David Friedberg? So you can't hear yourself speaking? How do you rationalize what's going on if you don't have a dialogue going on?
5:30 Speaker 01 It's this visceral feeling, like you're, you're hyper aware of what's happening. It's not like you, you block out in the first like, we take a very high dose. You don't really know what's happening the first few minutes, but then you kind of come to and you're hyper aware of everything. It's not visual, but it's this, um,
5:50 Speaker 01 you're in the depths of existence, like this.
5:59 Speaker 01 It's just the most majestic
6:03 Speaker 01 experience achievable by a human, by, by intelligent life. I just can't imagine anything more miraculous.
6:11 David Friedberg? You've studied the biology, the biochemistry, what goes on in the brain as this molecule hits your neurons?
6:18 Speaker 01 Yeah. So I mean, like it, um, I mean, one, it completely dissolves your default mode network.
6:25 David Friedberg? Describe what that is.
6:26 Speaker 01 So like, um, it's, this is the engine that constructs self and ego. And so as you ruminate, you know, like you're going through.
6:35 David Friedberg? Thinking through your day, what's next?
6:37 Speaker 01 Exactly.
6:37 David Friedberg? How am I feeling?
6:38 Speaker 01 Yeah.
6:38 David Friedberg? What should I be doing right now?
6:40 Speaker 01 Yeah.
6:40 David Friedberg? Constant conversation.
6:41 Speaker 01 Yeah. Do I feel bad about myself? Do I feel, you know, like I, am I shy? Am I like, do I feel bad about whatever? Like you're doing this rumination stuff. Uh, kids don't have this rumination loop. Their, their default mode network is, is quiet. And as you age, you basically build up this default mode network into more stiffer patterns. And so as you age, your experience of reality becomes increasingly narrow. You have these big ruts that form. And so you can just see people and their patterns, like how open a child is to say like very random things. And as adults, you're just very, you're shut in. Like when I did psilocybin. One of the reasons why we did it is because it does have this effect where it dampens the default mode network. And we could pick this up with Kernel, the brain interface. You can see how the default mode network weakens. So basically, think of the brain
7:25 Speaker 01 like a globe with airports scattered about, and you have certain traffic patterns like New York to London. You have a certain number of flights every day. That's like a very strong connection. But New York to some small town in Arkansas has a very low traffic map. And so when you do something like psilocybin, it basically takes the airports, picks them up, and then repositions them in the world. So it's all scrambled. So the traffic patterns aren't the same. And then over time-
7:52 David Friedberg? The neurons don't physically move, but the activity shifts around.
7:57 Speaker 01 Exactly.
7:57 David Friedberg? Right? The neurons are a little bit more random than they normally would be, which arguably drives neuroplasticity, causes those neurons to reach out for new connections. And when new connections are made, new behaviors, new ways of thinking emerge-
8:11 Speaker 01 Exactly right.
8:11 David Friedberg? -coming out of these therapeutics. Is that a fair way to describe it?
8:14 Speaker 01 Exactly right. So you look at my brain on psilocybin from Kernel, you see my patterns before, like the New York to London connection. You see my brain afterwards, and it's exactly what you said. New patterns are emergent. The old ones have quieted down. It's like a new map of connectivity. And so we saw that happen, and that does generate a lot of neuroplasticity.
8:32 David Friedberg? And obviously, this neuroplasticity rewiring these connections in the brain is what allows trauma victims or folks that have a certain wiring that they keep repeating in their brain, which causes the trauma and the anxiety in their lives to get rewired. And then that trauma and that anxiety feels like it dissolves or melts away. Is that a fair-
8:51 Speaker 01 Exactly right.
8:52 David Friedberg? Yeah.
8:53 Speaker 01 Yeah.
8:53 David Friedberg? And so this has been documented in psilocybin. It's kind of well-understood. How did you connect that psilocybin data to an effort in longevity? Or was this just like a random idea? Let's try it out?
9:05 Speaker 01 Yeah. So we saw some mouse data that it had these effects. It also showed reduced inflammation. So we said, like, this is interesting, because most longevity therapies do something with inflammation, right? Like, inflammation is the killer. So if you can lower inflammation, a very good sign. You can do something that makes the brain more youthful and takes down those those big ruts. That's also useful. What we found at psilocybin, though, is that it had, we found a first in human observation. It had this this metabolic reset in the brain where my blood glucose before this was in the top ninety nine point five percentile of all the population.
9:42 David Friedberg? Okay.
9:43 Speaker 01 After it went to the top ninety nine point nine percentile, like to move my blood glucose to that level is very, very hard. But basically, like, not like metformin where you're doing something on blood glucose. This just had a reset across the body, also changed my microbiome. Uh, so we saw full on effects. So then we said, okay, if that had that consequence, five M E O may have some similar characteristics.
10:04 David Friedberg? And so no one had done this in five M E O before.
10:06 Speaker 01 Exactly. So there's like, there's, there's animal evidence. But it's the the similar dynamics of like, can you take the brain? And can you basically like smooth out the barnacles that accumulate? And five M E O D M T compared to psilocybin, like, just absolutely like blasted clean. My default mode network. It felt like psilocybin dampens it, like it softens it, but this thing just annihilated my default.
10:34 David Friedberg? Turned it off completely. Yeah. It just, it just doesn't run the same way.
10:38 Speaker 01 Like, for an example, like, uh, this morning I woke up, uh, catching myself laughing in a dream. I have not laughed in a dream. I don't even know when I've ever laughed in a dream. But that is, after I woke up, I was like, that's really weird. Like, I don't remember laughing. I looked it up. Like, that is a characteristic of a child.
10:55 David Friedberg? Right.
10:56 Speaker 01 And so you are restored to this childlike state. And I mean, the past couple of days, I have felt childlike, you know, yesterday morning, I felt that, you know, that emergent excitement, the bubbling of like, today's so exciting. I'm going to do new things. I'm going to have new experiences. Um, that you're just excited about all things. I haven't felt that. I don't even know when, you know, for so many years. So like, it really was, um, profound on every layer. And I see, and I'm stumbling too, because I didn't even talk about it yet.
11:27 David Friedberg? During the day, you're hanging out, you're walking around. Is your brain having the same normal chatter that it did before? Or do you think that there's a persistent change in that default mode network?
11:38 Speaker 01 Yeah, definitely a change. Like, I was with my partner Kate yesterday and we, um, I did something that. Made her upset. And so like in that situation, you know, like when when couples are in that moment, you have like this negotiation, how do I sort this? And it all just became so clear to me, like when children have a fight, you have it out and it's just like done. Yeah. And you move on. But then adults take that and they like package it up and like they want to weaponize it be like, I got something on you. And I'm like move it. I'm going to move the chess pieces and like try to leverage this and and. Or they stored up like a snake in one of those things that pops out all the snakes later. Exactly. Package it all up.
12:19 Speaker 01 Exactly. And so like we had this and I I just felt absolutely like no need to escalate or to defend or to like, it was just easy. And it was a breakthrough in our relationship where I was able to communicate with her in a way. And so it's like laughing in my sleep. It's how I deal with my partner when I walk around. I just feel so much I I feel so much more funny, you know, like my ability to make quips that are just immediate. You know, like, so yeah, I just feel renewed as a person in a way that I just really didn't imagine. Have you tried hallucinogenics before you started your longevity path a couple of years ago? Yeah.
13:04 Speaker 01 And did you do that recreationally or therapeutically? It was mostly therapeutic in that. Yep. I I had sold my company, Branche of M O. I got a divorce. I left the Mormon church. And I was trying to remap like, what is life? Who am I? What do I do? So I was in that rebuilding stage where I just dabbled of like, you know, I did I did ketamine at Colonel. So when one of our first studies at Colonel is we said ketamine was a up and coming therapy for depression. And we posed the question, what happens when you do ketamine? And so we did the world's most extensive measurement of ketamine with Colonel before, during and after. And so that was interesting, like, and it had some kind of, you know, transient effect, but that's like a
13:44 Speaker 01 like a little league relative to. 5MEO.
13:47 David Friedberg? And so as you've gone through this, maybe share a little bit of the MRI data that you're gathering and the other data mapping neurological effects.
13:54 Speaker 01 Yeah.
13:55 David Friedberg? And tell us a little bit about what you've learned.
13:57 Speaker 01 So far, nothing. I have my subjective experience to share, but we have a structural brain MRI. We have a functional brain MRI. We did Kernel, which is like an optical interface. And then I did a real-time EEG capture.
14:10 David Friedberg? And we should just talk about, I think it's important, structural, you can see the physical brain. Functional, you can see the activity in the brain. So neurons firing and neurons that are not firing.
14:22 Speaker 01 Yes.
14:22 David Friedberg? Right?
14:22 Speaker 01 Yeah.
14:23 David Friedberg? And then electrical actions that are measured by an electrical device.
14:27 Speaker 01 So we basically like wanted, because the brain is very, so we've had a lot of success rejuvenating my heart and my lungs and muscle and body fat. But rejuvenating the brain is very hard.
14:38 David Friedberg? Right.
14:39 Speaker 01 And so we, this is why this is such a promising therapy. So we wanted to look at the brain through every modality possible. We wanted to look at blood flow, structural, molecular, you know, the wave pattern form. So it's a, it's a very high fidelity quantification. And so we'll see what the data comes out. I'm very excited. Yeah.
14:57 David Friedberg? You did this on psilocybin as well, right?
14:58 Speaker 01 Yes.
14:58 David Friedberg? You mapped the brain over time. What did you learn there?
15:01 Speaker 01 Dramatic restoration of youthful brain patterns.
15:06 David Friedberg? Yeah, right.
15:06 Speaker 01 Yeah.
15:07 David Friedberg? And what comes after 5MEO? I mean, how far do you take this?
15:14 Speaker 01 Yeah. Honestly, I am so encouraged by psychedelics. I, you know, again, in the community where I hang out, psychedelics have always been understood as, you know, it's like a retreat or it's like a ritual or you go to like do various explorations, but never in the world of longevity. It's never been understood as that thing. And now after seeing the data, now I am.
15:44 Speaker 01 And of course, you have to be very careful when talking about psychedelics because they're extremely powerful. It's not like go out and do them everybody, right? It's like it needs to be done properly with a licensed professional. It needs to be done carefully. The person needs to be in the right state. Like it is not to be taken lightly, but I am more interested than ever in psychedelic compounds. They're just uniquely powerful.
16:04 David Friedberg? There's some arguments to be made that psychedelics can induce permanent psychosis, cause functional changes and drive some people that might be predisposed into schizophrenic states.
16:17 Speaker 01 That's right.
16:17 David Friedberg? How did you get over those risks? Because for a lot of people, that would turn them off to trying psychedelics. And it's not a non-zero percentage of people that suffer these consequences.
16:28 Speaker 01 Yep, I agree. And also people who have really bad trips that leave them scarred. So it's, it really is. And I think in part of it is what could be contributing to this is people who, for example, who have tried magic mushrooms, you know, it's in a social situation. Someone's got a bag. You pull out some mushrooms. It's like, yeah, like ways blank. And they pop it in, but they have no idea what kind of mushroom strain they're eating. They don't know what the dose of psilocybin is. So it's like unquantified, unsupervised, wrong sentence setting. And so much of it, I think you can, the risk persists. But I don't think we've approached psychedelics with the appropriate rigor that we should to make it safe. And so it's not to say that we can solve for the safety issues for all
17:10 Speaker 01 people. Some people may not be the appropriate candidate for it. But I think if we do create a safety structure around it, they could deliver the benefits people want without, you know, with less of the risk. But definitely, I agree with you. Like it's, again, it deserves all the caution in the world.
17:27 David Friedberg? Do you think it's like neurogenic, neuroplasticity, trauma resolution? I mean, what is the way that this is going to be allowed to become, call it a medical therapeutic that can be more broadly trialed and then eventually figure out how to bring it to people without it being, carrying all the risks and burdens that it does today?
17:46 Speaker 01 I mean, if I just subjectively compare my experience with 5MEO to having a better diet and exercising every day and sleeping well and doing the sauna and doing hyper red oxygen therapy. This was more efficacious than all of them in terms of the reset of me as a human. It just is incomparable. And I guess I'm really left pondering for this molecule to have such a gigantic impact. Now, like, how long will it last? What's the decay curve like? You know, will I find I I become the former Brian within 30 days, 60 days? I have to repeat this again? I don't know. But it really is, you know, when you sleep well, you feel great. You exercise, great.
18:30 Speaker 01 But like, nothing like what 5Mio did in terms of of like the reset of me as a human.
18:35 David Friedberg? So let's just talk about the consequences outside of the physiological, which is life.
18:41 Speaker 01 Yeah.
18:42 David Friedberg? There are lots of stories and friends that I have that and people that I know that have tried a heavy psychedelic, like an ayahuasca or something. They were the CEO of a company and then they quit their company and they go off to the jungle, leave their family, divorce their their partner. Makes such dramatic life changes because their perspective has been shifted so much that they reevaluate what matters in life to such a degree that they give up a lot of the things that mattered before.
19:11 Speaker 01 Yeah.
19:12 David Friedberg? In the wake of that, there are people that feel they're a victim of that behavioral shift. The investors in the company, the employees, the family members, et cetera.
19:23 Speaker 01 Yeah.
19:24 David Friedberg? Can you just talk a little bit about those broad risks? Because we've seen it and I don't know if you've seen the same. But friends that have kind of like said, I have this new perspective. I'm giving up my life.
19:34 Speaker 01 I've seen the same thing. And I, um, one investor told me that he even put it in the deal docs. That, you know, if we invest, you're not going to do these psychedelics. Because they wanted to minimize the the risk profile. It's a thing.
19:47 David Friedberg? In your deal, in an investment in you?
19:48 Speaker 01 No, I just spoke because I've been doing this.
19:52 Speaker 01 People bring this up as a topic of conversation.
19:54 David Friedberg? Right.
19:55 Speaker 01 And so they say like, I see you're doing this for longevity, but you know, like I've seen so many examples where people put money in, then you lose the founder. Like they're off.
20:04 David Friedberg? They're gone.
20:05 Speaker 01 Everyone's high and dry. And so they were telling me that they put into DILTOX that they can't do this for the duration of the company. And so it is a thing and you know, I, I have nothing to say about it other than I know what happens. Um, also I would say that most people in the tech world that I'm familiar with, again, they've done this in retreat centers or in social environments. It's not quantified, it's not set in setting, it's, so it's a different thing. But I will say like, you know, I, I guess me as a person, what I'm trying to focus on, I came back even more motivated to do what I'm doing now. Uh, I don't have a desire to go off in the woods, you know, and like, and live that kind of life.
20:48 Speaker 01 It, it, it emboldened me to work on these things, but no question about it. You, you do have a dramatic shift in perspective and it's, it's very hard to get.
20:57 David Friedberg? It begs a very important philosophical question. Who am I?
21:01 Speaker 01 Yes.
21:03 David Friedberg? If I'm defined by my experiences, it roughly equates to my neurons are wired in a way.
21:12 Speaker 01 Yes.
21:13 David Friedberg? That's a consequence of my experiences. And if I go in and take a drug and in a few hours rewire all my neurons, am I the same person?
21:21 Speaker 01 Yeah.
21:21 David Friedberg? What makes Brian Brian? You can maybe recall some memories of Brian prior to taking the psychedelic, but Brian as a person has been rewired.
21:31 Speaker 01 Yes.
21:31 David Friedberg? Are you a different person now? And what does that say about, are we ever a persistent person?
21:36 Speaker 01 Yeah.
21:37 David Friedberg? Right?
21:37 Speaker 01 Yeah. Your question is spot on. Probably the most dramatic reconstruction of your 60 plus trillion cells than anything you can do in life. You know, like maybe like a near death experience, you know, would, would maybe be close, but it's a dramatic rewiring of you as a, as a human.
21:55 David Friedberg? Your values can change too.
21:56 Speaker 01 That's right.
21:57 David Friedberg? And you could judge the values pre and post, right? You could judge values ascribed to you by a religion, or perhaps values ascribed to you by responsibility to family members, children, spouses, partners, what have you. You abandon them after you go through this change. So your values have changed. Is it right or wrong?
22:16 Speaker 01 That's right.
22:17 David Friedberg? I think it's another important question that comes out of all this.
22:19 Speaker 01 I agree. And like you now, like you now think about that. That's through the frame where the world changes at a certain speed. Now you take the world where it's changing faster. So we now know that it's hard to predict what's going to happen two weeks from now or a month, right? Like, things are changing very quickly. And so now you come up with this practical question. Can humans change fast enough in the world where AI is the dominant engine of innovation? And so in that case, you may want psychedelics as your ally to say, as a human, I'm struggling to move with the change.
22:54 David Friedberg? Yeah.
22:55 Speaker 01 And so there's potentially where it flips from a liability to an asset where now I do want that restructure changing, even though you have some tail risk of like, maybe my priorities will shift.
23:06 David Friedberg? I think you have profound, what I would call psycho flexibility. And I think most people don't. They have either a disinterest in changing who they are overnight or they're fearful of the ramifications or the experience and that they wouldn't go through it. How far would you take it? Would you wire yourself up to a Neuralink or neural enhancement device that would give you the ability to have information on demand and maybe change your personality and capacity as a human through an implant? Would you consider doing something like that? You would? Would you consider a transgenic system where you basically take a plasmid, which would then express a set of proteins in your body and change gene expression profiles and cells in your body and basically could rewire you as a different person?
23:51 Speaker 01 Yes.
23:51 David Friedberg? Yes. Is there a limit to what you would try?
23:53 Speaker 01 No.
23:53 David Friedberg? Interesting. Where do you think that comes from?
23:55 Speaker 01 I think I find it to be the most exciting configuration of life. The ability to play on the frontier. Novelty and expedition and challenge.
24:08 Speaker 01 That's really my.
24:09 David Friedberg? Did you always have it or are you responding to childhood suppression of those?
24:15 Speaker 01 It's probably it's probably an overcompensation of of trauma response like most things are. And so, you know, as a child, I lived in a very structured religious environment where things were cemented. Like, here's the story, here's the plan, here's what you do and what you don't do.
24:28 David Friedberg? Yeah.
24:29 Speaker 01 And so, yeah, maybe it's probably just I'm now flipped in the opposite.
24:33 David Friedberg? Yeah.
24:33 Speaker 01 And so, I mean, that's probably true that I really, I don't trust my internal generation of reality.
24:40 David Friedberg? Yeah.
24:40 Speaker 01 You know, I know I'm always making things up. I've got one hundred and eighty eight chronicle biases like all humans do. So I'm just, I'm generally suspicious of all things all time and I don't take myself very seriously. So I just find the frontier play space to be like, right now, I mean, you know, what you're doing in building companies? Like, you just open up a toolkit and say, like, what can I build? And how do I modify? And so I agree with you, I do have a strong proclivity towards openness play.
25:06 David Friedberg? Do you find that you've been challenged in maintaining, I would call it, external responsibility? As you explore and enhance yourself so much? Do you give up the responsibility to others around you who maybe are dependent on you or in need of you?
25:19 Speaker 01 Yeah, I have three kids. And so I do think about them a lot. And I, being a father is a really important thing to me and it's an important part of my identity. And so that has not changed. So I've never vacillated on that or changed my disposition towards that. For those around me, I guess fortunately I have a a social group that just says, go and play. There's, there's really no one in my life that tries to claw me back. There's no Velcro.
25:47 David Friedberg? Yeah.
25:48 Speaker 01 It's just all encouraging. And so that, I guess I feel very fortunate that everyone around me, and they're willing to take the risks. I mean, this is, when I sat down for five MEO, I mean, my partner Kate, like, she's got. A ton of risk. Like, what if it goes poorly? What if I change my perspectives? What if something bad happens? So.
26:05 David Friedberg? Well, one could make an argument that taking that degree of risk where something could have gone wrong, the people around you are enabling versus being supportive, right?
26:13 Speaker 01 That's right. That's right.
26:14 David Friedberg? I mean, that's a consequence, but let's shift topics to other
26:20 David Friedberg? modalities for longevity.
26:22 Speaker 01 Yeah.
26:23 David Friedberg? What else is on the horizon? So you've had this profound set of experiences with psychedelics. You've documented in a very extraordinary and exquisite fashion, all of the other things that you've been doing. The interventions, are there other things that are on the horizon that you're either excited about or that you're considering yourself?
26:39 Speaker 01 Yeah, I mean, two of the ones that we've spoken about, cell therapy and gene therapy.
26:42 David Friedberg? Yeah.
26:43 Speaker 01 Yeah, they they're all in the pipeline, so they're not ready yet. We've we've knocked out all the stuff you can do today. Like, we've gone through it all, done it all. The next gen therapies are just not there yet. So we're looking at mitochondrial rejuvenation.
26:57 David Friedberg? I think that's incredible. I think mitochondrial augmentation therapy. And there was a paper I saw where in order to get the mitochondria in the cell, they coated the mitochondria in effectively a red blood cell envelope, which made it more transportable into cells and less attacked by the immune system.
27:13 Speaker 01 Exactly.
27:13 David Friedberg? Which is incredible. And I'm a big, big, big believer in this this this course of therapy. I mean, this is going to be a whole therapeutic modality that no one has even recognized.
27:22 Speaker 01 I agree. We have our first mitochondrial therapy lined up, so.
27:25 David Friedberg? How are you going to do it? You're like 99.9%. You need someone who's like 48.7% to try the mitochondrial.
27:32 Speaker 01 I agree with you.
27:33 David Friedberg? Particularly like, you know, I think they tried it in Parkinson's patients, Alzheimer's patients. That's where you could really see profound shifts in in certain metrics. For you, it's like 99.9% to what?
27:43 Speaker 01 Like, yeah, I have the mitochondria, you know, of a 48-year-old, right? So like, what if I?
27:48 David Friedberg? That's right.
27:49 Speaker 01 What if I could? Yes.
27:50 David Friedberg? You could go to your sibling's child because the mitochondria is passed maternally.
27:55 Speaker 01 Yeah.
27:56 David Friedberg? Because it's in the egg cell.
27:57 Speaker 01 Yeah.
27:57 David Friedberg? So it's the mother's mitochondria. So if you go down the mother's line maternally, if you have a sister who has a kid, they're going to have very young mitochondria. You can take a little blood sample and then grow their mitochondria extensively and use that as a biological match to you.
28:12 Speaker 01 This is a perfect extension. I've had a blood boy as a son.
28:15 David Friedberg? Yeah.
28:16 Speaker 01 So now I'm just going to go to the extended family and be like, guys, it's a family project.
28:21 David Friedberg? Yeah, family project.
28:21 Speaker 01 Yeah, exactly.
28:22 David Friedberg? Yeah. Well, that one's super interesting.
28:24 Speaker 01 We also have one that we're doing. I'm now building.
28:27 David Friedberg? Sorry, are you going to do your own mitochondrial transplantation? You're going to build a bioreactor or are you working with one of the third parties?
28:32 Speaker 01 Yeah, a third company. Yeah, so I'll do a blood draw in the next week or two. They'll spin up.
28:37 David Friedberg? They'll do it?
28:37 Speaker 01 Yeah.
28:38 David Friedberg? Okay.
28:38 Speaker 01 Yep.
28:39 David Friedberg? So you're going to get your mitochondria, which have some, you know, the problem with mitochondria, as you know, is mitochondrial DNA degradation over time, right? It accelerates for certain people, but that way, if you go back to a young person, you have young mitochondria.
28:52 Speaker 01 Exactly right.
28:53 David Friedberg? Then you're going to multiply yours out.
28:54 Speaker 01 Yes.
28:55 David Friedberg? And probably select a little bit or healthier ones?
28:57 Speaker 01 Exactly right.
28:58 David Friedberg? Right, okay. And then put it back in.
28:59 Speaker 01 It's very explorative. We don't know. We're one of the first. They're in phase two now.
29:04 David Friedberg? Do you sprint?
29:05 Speaker 01 Yeah, I do.
29:06 David Friedberg? So you could probably score if you did it intramuscular, like mitochondrial there. You could sprint and see your score.
29:11 Speaker 01 That's a great idea.
29:12 David Friedberg? Yeah, thank you.
29:13 Speaker 01 Yeah.
29:13 David Friedberg? That would be a great way to measure it rather than just a basic biomarker perspective. Be really interesting to see.
29:20 Speaker 01 Yeah. Sprinting is one of the most underappreciated longevity therapies.
29:23 David Friedberg? Yeah, I don't do it.
29:25 Speaker 01 Oh, man.
29:25 David Friedberg? I've got the age of a 74-year-old, roughly.
29:29 Speaker 01 Is that right?
29:32 David Friedberg? I'm definitely not keeping track with you. Would you consider, or have you looked at any plasmids where you take a gene as DNA, put it in your body, and then that gene makes a protein in your body that does something?
29:44 Speaker 01 Like the one we were looking at in the Foxal3 expression? Yeah, exactly. So the mesocellular stem cells packaged up with the Foxal3 delivery, that showed that over 50% of tissues getting that rejuvenation.
29:54 David Friedberg? It's unbelievable.
29:55 Speaker 01 It's like the.
29:55 David Friedberg? Unbelievable.
29:56 Speaker 01 It's the best demonstration in the entire world.
29:58 David Friedberg? That's perfect for tissue regeneration, like as a particular application set, tissue regeneration, using that sort of system.
30:03 Speaker 01 Seems like a no brainer.
30:04 David Friedberg? It's like, yeah.
30:05 Speaker 01 It's safe, right? Yes, I reached out to that Chinese professor. I'm really interested in seeing it replicating. I would love.
30:12 David Friedberg? You reached out to the Chinese professor?
30:14 Speaker 01 Yeah.
30:14 David Friedberg? That's awesome. We sent that paper.
30:16 Speaker 01 Yeah, yeah, exactly.
30:17 David Friedberg? Yeah, that's awesome.
30:18 Speaker 01 So.
30:19 David Friedberg? Did he respond?
30:19 Speaker 01 Uh, yeah.
30:20 David Friedberg? Awesome.
30:20 Speaker 01 Yeah.
30:21 David Friedberg? Good.
30:22 Speaker 01 So we, I'd love to do that. I'd love to actually build it ourselves.
30:26 David Friedberg? Yeah.
30:26 Speaker 01 But that's like a two year project, so.
30:29 David Friedberg? AI can help make it faster.
30:30 Speaker 01 That's true.
30:31 David Friedberg? Yeah.
30:31 Speaker 01 Actually, that's true.
30:31 David Friedberg? AI as a project manager for these sorts of programs is.
30:34 Speaker 01 You know, that's true. We, we spoke about this six months ago.
30:37 David Friedberg? Yeah. And things are so different.
30:38 Speaker 01 So different now, six months later, and in terms of stand that up. So that was cool. So I think that's a good, good option. But also I'm doing Brian Johnson organoids. So we took my IPSEs. We now have them.
30:49 David Friedberg? Infused pluripotent stem cells.
30:50 Speaker 01 Exactly.
30:51 David Friedberg? So you took your cells, turn them into stem cells.
30:53 Speaker 01 Yep.
30:53 David Friedberg? Yeah.
30:53 Speaker 01 So now we're doing in dish. So now we have like a Brian Johnson heart, liver, lungs. And now we're going to try molecules on me and in.
31:00 David Friedberg? So you have a plot. So, so let me just walk the audience through this. So you take cells off of your skin or something.
31:04 Speaker 01 Blood.
31:05 David Friedberg? Blood. And then you put these yamanaka factor proteins on those cells. Causes those cells to become stem cells, which means they can then turn into any other cell.
31:12 Speaker 01 Yeah.
31:12 David Friedberg? And then you put other proteins on them to turn them into a heart cell or a eye cell or what have you. And now you've got a store of these tissue specific Brian Johnson cells.
31:23 Speaker 01 Yes.
31:23 David Friedberg? That you then use for.
31:25 Speaker 01 Like you can say, okay, what if you get Brian Johnson blank, you know, drug? What is, what happens? Is it good? Is it bad? What are the side effects?
31:33 David Friedberg? In the PT dish, you put the drug in there.
31:35 Speaker 01 Exactly.
31:35 David Friedberg? See what happens.
31:35 Speaker 01 Yeah.
31:36 David Friedberg? Okay.
31:36 Speaker 01 So you're like, you can simulate all these experiments. So now you, you get the advantage of time, of acceleration of like what to take, why, what dose.
31:43 David Friedberg? That's awesome.
31:44 Speaker 01 What combinatorial things to consider.
31:45 David Friedberg? Yeah.
31:46 Speaker 01 And so we, we have the organoids stood up. We haven't done our first takes yet.
31:48 David Friedberg? Yeah.
31:49 Speaker 01 So that's interesting because now I have to do this old school methodology, like put it in my body, wait to see what happens. Is it good? Is it bad? What, you know, how does it affect everything else?
31:58 David Friedberg? Yeah, totally.
31:59 Speaker 01 That's a good one. But I mean, I don't know. We'll see. It's cool in concept. I mean, TBD if it actually works, so we'll see.
32:05 David Friedberg? Have you tracked any of the alternatives to Yamanaka factors, the factor discovery work that's going on? And do you think there's anything worth testing at this stage?
32:13 Speaker 01 Yeah, I'm an investor in New Limit, so I've talked to them about where they're at.
32:17 David Friedberg? Blake and Brian's company.
32:19 Speaker 01 They've done, I mean, they've made remarkable progress.
32:22 David Friedberg? Yeah.
32:23 Speaker 01 They figured out how to computationally solve the discovery process.
32:27 David Friedberg? Yeah.
32:27 Speaker 01 And so they're much faster than they initially thought, and so that's very encouraging.
32:31 David Friedberg? You know, the big challenge with Yamanaka factors is always dosing. If you overdose a cell, a one cell, that cell can become a cancer cell and take off as a tumor.
32:41 Speaker 01 Yeah.
32:41 David Friedberg? So the sensitivity that you need to have to get the right number of the factors, which is a protein into the cell, needs to be perfectly tuned.
32:49 Speaker 01 Yep.
32:49 David Friedberg? So I have a theory that this will end up being solved by cellular switches. That will end up putting machinery into the cells that can turn on or off the protein synthesis at the right dosing, based on the measurement of gene expression in the cell.
33:03 Speaker 01 Yeah.
33:04 David Friedberg? That's my theory on where this will end up.
33:06 Speaker 01 That makes a lot of sense. Any other control mechanism will be inadequate.
33:09 David Friedberg? That's right.
33:09 Speaker 01 The feedback loop just...
33:10 David Friedberg? All you need is one error and you're trouble.
33:12 Speaker 01 Yeah.
33:13 David Friedberg? But it is, it is the most profound, I think, technology that humanity is dealing with today besides AI. We're not quite there with fusion, which I would argue is probably a distant third, but it is very powerful.
33:22 Speaker 01 I agree.
33:22 David Friedberg? What's possible.
33:23 Speaker 01 And in the future, like, I think we'll look back and we'll see GLP-1s as the first big drop.
33:28 David Friedberg? Yeah.
33:28 Speaker 01 Of like, what, I can just inject myself and like it solves hunger and...
33:31 David Friedberg? Totally.
33:31 Speaker 01 Yeah, and then the second will probably be something like New Limit or one of these fox, one of these plasma-based FoxO3 therapies where it will show real life, like dramatic changes.
33:41 David Friedberg? Totally.
33:42 Speaker 01 And then humanity will shift as like longevity being a vision of sci-fi, you know, rich people pursuit to like something that is truly, I mean, go back to like the conversation on, on the temptation towards socialism. Right? Like if you can feel robust in your ability to pursue life and be healthy and vibrant and in control, I think these things would have dramatic changes to society, not just in health, but like...
34:09 David Friedberg? Well, any form of abundance, whether it's abundance in food, in energy, in housing, in mobility, in lifespan. The more abundance people get, the happier they are.
34:17 Speaker 01 Yes.
34:18 David Friedberg? And the more you're improving abundance in the world, the better we are going to live as a group of people together on planet Earth.
34:25 Speaker 01 Exactly.
34:25 David Friedberg? The happier we will all be with each other.
34:27 Speaker 01 I think honestly, like a lot of the.
34:29 David Friedberg? External conflict only comes from internal unhappiness.
34:32 Speaker 01 Hundred percent. So if you look at the general malaise of like American society, like no wonder uh things are shitty, right? Like you've got 84% of people have metabolic disorder. More than 40% of people are obese. Like we're just in really poor health. Nobody's sleeping. Everyone's on their phone. We have mental health issues. Like no wonder you have the proclivity towards these kinds of outcomes. Like so if you could get the health in check, it changes the psychological disposition of you, your community, your country. Like you have much more of a can do attitude. Like I can take on the world and I can do hard things. But when you're not feeling well, like it's just, everything is just so much harder.
35:06 David Friedberg? Yeah, 100%. And so in light of all of these new therapeutic modalities and these new opportunities that seem to be biologically proven and have these profound effects, why continue to tinker with psychedelics? Like are they as profound or are they a compliment? Or like, how do you think about fitting all of this portfolio of things that you're looking at together?
35:24 Speaker 01 Yeah. I mean, I guess the question is, um, I forget on the Foxhole 3 study. I don't know if they saw brain rejuvenation.
35:29 David Friedberg? Didn't see that. I did not see that. And I don't, I don't remember. I mean, it is a very complicated organ.
35:35 Speaker 01 Yeah, exactly.
35:36 David Friedberg? It's insane.
35:37 Speaker 01 It's very hard to reach.
35:38 David Friedberg? You know, you can grow muscle tissue back and you can grow skin tissue back. And it's kind of like, okay, I grew a little X. Like if you grow the neurons back, maybe in the wrong way, like we don't know.
35:49 Speaker 01 Yeah.
35:50 David Friedberg? Because it's never been done before.
35:51 Speaker 01 Yeah.
35:52 David Friedberg? So understanding the consequence of neuro regeneration is like.
35:57 Speaker 01 So I wonder like if the role in my play, like, you know, maybe psilocybin and 5-MEO won't be um, you know, meaningful for like basic functions of the body. But maybe it's the uh, the outperformer in usefulness of your, of your disposition towards reality. Like one thing I'm apprehensive about is I'm 48. And so as you start climbing to your 50s, 60s, you do really narrow. Like your ambition goes from I can do anything to start, you know, narrowing down further and further and. I worry about using, losing a youthful disposition of a can do attitude of anything is possible.
36:40 David Friedberg? Totally.
36:40 Speaker 01 And maybe that's the role psychedelics is you just get awash of like the snap back of like, I can and I can bounce.
36:48 David Friedberg? Yeah.
36:48 Speaker 01 That definitely been the case for me. So I think they do probably play a really important role of like, they're probably a set of things that for certain people that will, um,
36:59 Speaker 01 basically like, I mean, I felt like it was like thirty, forty years of
37:06 Speaker 01 psychological rejuvenation. Like, you know, it's like to transport me back to a childlike state.
37:10 David Friedberg? Yeah.
37:10 Speaker 01 That is insane. I don't get that from the sauna.
37:12 David Friedberg? Yeah.
37:13 Speaker 01 Or from eating well, or from sleeping well. Like, I'm still.
37:15 David Friedberg? Right.
37:16 Speaker 01 So it's just unique.
37:18 David Friedberg? Yeah, amazing. Well, listen, I'm gonna go drink alcohol and eat carbs and stay out late. I don't know. What are you gonna do?
37:24 Speaker 01 Yeah, I'm gonna go to bed on time. Yeah.
37:26 David Friedberg? Okay.
37:27 Speaker 01 Do my wind down routine.
37:28 David Friedberg? Yeah, you do you.
37:29 Speaker 01 Yeah.
37:29 David Friedberg? But.
37:29 Speaker 01 You as well. Enjoy it.
37:31 David Friedberg? Yeah. I appreciate it. This has been great. Brian Johnson. Thank you.
37:34 Speaker 01 Thanks.
37:34 David Friedberg? Yeah, that was awesome.
37:35 Speaker 01 That was great.
Previous Four CEOs on the Future of AI: CoreWeave, Perplexity, Mistral, and IREN Next Anthropic's Generational Run, OpenAI Panics, AI Moats, Meta Loses Lawsuits Page updated October 3, 2026 · transcript and summary are machine-generated
