Bryan Johnson: I Just Took the Most Powerful Dose of DMT in the World... Here's What It Was Like

26 Mar 2026 · 38 min · 16 chapters

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In short

Bryan Johnson (longevity entrepreneur) argues psychedelics—especially 5-MeO-DMT—may be “longevity therapy” by rapidly resetting the brain’s default mode network, boosting neuroplasticity, and producing a childlike, less-ruminative mindset that could support healthier aging.

Guest backgrounds

Bryan Johnson is the founder of Kernel and runs a quantified longevity project using interventions ranked by evidence (exercise, nutrition, sleep, then sauna/hyperbaric oxygen, rapamycin, metformin). He also uses brain mapping tools (structural/functional MRI, Kernel optical interface, real-time EEG).

Key claims

5-MeO-DMT “annihilated” his default mode network; psilocybin dampens it and “repositions” connectivity. He links psychedelic effects to reduced inflammation, metabolic “reset” (blood glucose), and microbiome changes. He stresses safety: unquantified, unsupervised use increases risks (psychosis, bad trips).

Notable examples

his live-streamed 5-MeO experience (9 mg IM + vaporized dose; onset ~10 seconds); “laughing in a dream” as childlike; relationship conflict resolved without escalation. He also discusses mitochondrial therapy, organoids, and gene/cell therapies as future longevity modalities.

Written by AI. May contain mistakes. Listen to the episode to check what was said.

Chapters

Tap a time to open that second in VO

Exploring the Decision to Use Psychedelics

0:54 to 2:10

Bryan explains his motivation behind trying psychedelics as a longevity experiment.

“Before we get into your experience, why did you choose to do it?”

Describing the 5-MeO-DMT Experience

2:10 to 4:53

Bryan shares his profound experience with 5-MeO-DMT and its effects on consciousness.

The Science of Psychedelics and the Brain

4:53 to 8:52

Discussion on how psychedelics impact the brain's default mode network and neuroplasticity.

“this, but if I list out the most dynamic experiences I've had of a human, like certain accomplishments or getting married or having a child or overcoming a difficulty or state your list of things.”

Linking Psychedelics to Longevity Efforts

8:52 to 14:02

Bryan connects findings from psychedelics to the potential for longevity and rejuvenation.

“And so this is, this has been documented in psilocybin.”

Exploring Brain Rejuvenation Techniques

14:02 to 14:58

Learn about advanced brain imaging techniques and their impact on rejuvenation.

The Role of Psychedelics in Longevity

14:58 to 17:46

Discover how psychedelics are seen as a potential tool for brain rejuvenation and longevity.

“It's never been understood as that thing.”

Impact of Psychedelics on Personal Transformation

17:46 to 18:34

Hear about dramatic life changes observed in individuals after psychedelic experiences.

“And I guess I'm really left pondering for this molecule to have such a gigantic impact.”

Risks and Philosophical Questions of Psychedelic Use

18:34 to 20:56

Examine the potential risks of psychedelics and their philosophical implications on identity.

“So let's just talk about the consequences outside of the physiological, which is life.”

Psychedelics as a Tool for Coping with Rapid Change

20:56 to 22:47

Discuss the potential of psychedelics to help individuals adapt to fast-paced societal changes.

“It begs a very important philosophical question.”

Balancing Psychedelic Exploration with Responsibility

22:47 to 26:20

Delve into the impact of personal exploration on familial and social responsibilities.

“Would you wire yourself up to a neural link 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?”
Show all 16 chapters

Future Modalities for Longevity

26:20 to 28:00

Explore upcoming therapies for longevity beyond psychedelics, including mitochondrial rejuvenation.

“So you've had this profound set of experiences with psychedelics.”

Exploring Mitochondrial Transplantation

28:00 to 29:00

Learn about the potential of using young mitochondria for health benefits.

“Yeah, so I'll do a blood draw in the next week or two.”

Innovations in Stem Cell Research

29:00 to 30:54

Discover how induced pluripotent stem cells can be applied in medical research.

“But also I'm doing Brian Johnson organoids.”

Challenges in Gene Therapy

30:54 to 32:38

Understand the complexities and risks involved in gene therapy treatments.

“So now we have like a Brian Johnson heart, liver, lungs.”

The Future of Longevity Technologies

32:38 to 34:28

Explore the implications of emerging technologies on human lifespan and health.

“Any other control mechanism will be inadequate.”

The Role of Psychedelics in Wellbeing

34:28 to 37:14

Examine how psychedelics could impact mental health and personal outlook.

“Like you have much more of a can-do attitude.”
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Transcript

Automatic transcript. May contain errors.

0:00Bryan Johnson, thanks for being here.

0:01Bryan Johnson:Yeah, it's good to see you. How are you feeling? Maybe just share with us what you did a few days ago. Yeah, I did 5-MeO-DMT, which is the most powerful psychedelic on the planet. It's somewhere between 5 and 10 times more powerful than DMT. And so, yeah, it's been 48 hours. I'm still learning how to talk about it. I'm going all in.

0:28You know what many of the biggest tech CEOs and VCs have in common? They sleep on the pod by 8sleep. It's become tech's favorite way to sleep and for good reason. A cover that goes on any mattress, cools it down to 55 degrees, and uses AI to adjust your temperature all night. Up to 34 % more deep sleep. No wearable needed. Go to 8sleep.com slash all in and use code all in for up to$350 off your pod purchase today. Before we get into your experience, why did you choose to do it? Two things.

0:58Bryan Johnson:One, mostly as a longevity experiment. So when I started this project five years ago, 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 for effect size, and we just went down the list from top performing on down. So of course, you start with exercise, nutrition, 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 being used in ritualistic practices or being pointed at things like depression and anxiety in certain trials.

1:42Bryan Johnson: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 25 milligrams of psilocybin. Which are pretty high doses. 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. Let's get to that data in a minute. But then you decided to try 5-MeO this weekend. Yes. walk me through the experience because you televised the whole thing it was live streamed you looked amazingly calm going into it and going through the process walk us through your experience yeah i think uh those who have done 5meo 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 committed you take that idea multiply it by a thousand and then move out infinite depth infinite width width and depth and then dimensions and like that gives you kind of like a rough map of like the size and space that you deal with and uh 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 you inhale it i did nine milligrams of intramuscular and then seven uh 18 of it of vaporized and it hit you within 10 seconds you're just out you're out and so um but what happens is you you get in that space and then visual changes very very little visual uh like you see on dmt it's a very visual you'll meet the you know like the elves or whatever else this is not a visual experience but you you 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 cut this the stream of existence is gonna just tear you to shreds it's gonna shard you and if you give up like break your brain yeah 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 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 it opened up this unimaginable bliss and euphoria.

4:52Bryan Johnson:And again, this is like a V1 of trying to explain this, but if I list out the most dynamic experiences I've had of a human, like certain accomplishments or getting married or having a child or overcoming a difficulty or state your list of things. This is without question, the most dynamic experience I've ever experienced as a human. Does the internal chatter, the internal monologue of the ego turn off? Does. So you can't hear yourself speaking? How do you rationalize what's going on if you don't have a dialogue going on? It's this visceral feeling like you're hyper aware of what's happening. It's not like you block out in the first like we think a very high dose.

5:39Bryan Johnson: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 you're in the depths of existence like this it's just the most majestic

6:04Bryan Johnson:experience achievable by by intelligent life i just can't imagine anything more miraculous you've studied the biology, the biochemistry, what goes on in the brain as this molecule hits your neurons? Yeah. So I mean, like it, I mean, one, it completely dissolves your default mode network. Describe what that is. So like it's, this is the engine that constructs self and ego. And so as you ruminate, you know, like you're going through. Thinking through your day. What's next? How am I feeling? Yeah. What should I be doing right now? constant conversation. Do I feel bad about myself? Do I feel, you know, like I, am I shy?

6:45Bryan Johnson:Am I like, do I feel bad about whatever? Like you're doing this rumination stuff. Kids don't have this rumination loop. Their default mode network 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 in 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.

7:19Bryan Johnson:And we could pick this up with kernel, the brain interface. You can see how the default mode network weakens. So basically like think of the brain, 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 around the world. So it's just all scrambled. So the traffic patterns aren't the same.

7:52And then over time - The neurons don't physically move, but the activity shifts around. Exactly. 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.

8:11Bryan Johnson:Exactly right. Coming out of these therapeutics. Is that a fair way to describe it? 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. 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.

8:47And then that trauma and that anxiety feels like it dissolves or melts away. Is that a fair? Exactly right. Yeah. Yeah. And so this is, 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

9:04Bryan Johnson:random idea let's try it out yeah it was so we 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 uh if you can do something that makes the brain more youthful and takes down those those big ruts that's also useful what we found in psilocybin though is it We found a first in human observation. It had this metabolic reset in the brain where my blood glucose before this was in the top 99.5 percentile of all the population.

9:43Bryan Johnson:After it went to the top 99.9 percentile. To move my blood glucose from that level is very, very hard. But basically, not like metformin where you're doing something on blood glucose. This just had a reset across the body. Also changed my microbiome. So we saw a full-on effect. So then we said, okay, if that had that consequence, 5-MeO may have some similar characteristics. And so no one had done this in 5-MeO before. Exactly. So there's like, there's potential, there's some animal evidence. But it's the similar dynamics of like, can you take the brain and can you basically like smooth out the barnacles that accumulate?

10:19Bryan Johnson:And 5-MeO DMT 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. Turned it off completely. Yeah. It just doesn't run the same way. Like for an example, like this morning I woke up 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 and like, that is a characteristic of a child. Right.

10:56Bryan Johnson: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 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 profound on every layer. and I see it I'm stumbling too because I don't even know how to talk about it yet 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 yeah definitely a change like with 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?

11:58Bryan Johnson:And it all just became so clear to me, like when children have a fight, you have it out and then it's just like done. And you move on. But then adults take that and they like package it up. And like, they want to weaponize it and 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 - Or they stored up like a snake in one of those things that pops out all the snakes later. You know, it's like package it all up. Exactly. and so like we had this and i i just felt um absolutely like no need to escalate or to defend or to like it was just easy and um 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 uh i feel so much more funny you know like my ability to make quips that are just immediate uh 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 and did you do that recreationally or therapeutically it was mostly therapeutic in that yeah i i had sold my company branch of mo 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 kernel so one of our first studies at kernel 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 kernel 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 a like a little league relative to 5mo 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 yeah and tell us a little bit about what you've learned so far nothing i have my subjective experience to share but we 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 and we should just talk about i think it's important structural you can see the the physical brain functional you can see the activity in the brain so neurons firing and neurons that are not firing yes right yeah and then electrical actions that are measured by a electrical device 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 right and so we this is why this is so such a promising therapy so we wanted to look at the brain uh through every modality possible we wanted to look at blood flow structural molecular you know the wave pattern form so we it's a it's a very high fidelity quantification and so we'll see where the data comes out um i'm very excited yeah you did this on psilocybin as well right you map the brain over time what did you learn there dramatic restoration of youthful brain patterns yeah right yeah and what comes after 5meo you know i mean how far do you take this yeah honestly um i am so encouraged by psychedelics i you know like in 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.

15:36Bryan Johnson:It's never been understood as that thing. And now after seeing the data, now I, 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. There's some arguments to be made that psychedelics can induce permanent psychoses. Yeah.

16:11Cause functional changes and drive some people that might be predisposed into schizophrenic states. That's right. 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.

16:28Bryan Johnson:Yeah, I agree. And also people who have really bad trips that leave them scarred. So 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 set and 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.

17:08Bryan Johnson:And so it's not to say that we can solve for the safety issue for all people. Some people just 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. 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?

17:46Bryan Johnson:I mean, if I just subjectively compare my experience with 5-MeO to having a better diet and exercising every day and sleeping well and doing the sauna and doing hyperbolic 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 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.

18:29Bryan Johnson:You exercise, great. But like nothing like what 5-MEO did in terms of like the reset of me as a human. So let's just talk about the consequences outside of the physiological, which is life. Yeah. 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 partner, make 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.

19:11In 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. 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.

19:34Bryan Johnson:I've seen the same thing. And 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 risk profile. It's a thing. In your deal, in an investment in you? No, I just spoke because I've been doing this. People bring this up as a topic of conversation. Right. 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 and you lose the founder. Like they're off. and now everyone's high and dry. And so they were telling me that they put into dildox that they can't do this for the duration of the company.

20:13Bryan Johnson:And so it is a thing. And I have nothing to say about it other than I know it happens. 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. So it's a different thing. But I will say like, you know, 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. I don't have a desire to go off in the woods, you know, and live that kind of life. It emboldened me to work on these things, but no question about it.

20:53Bryan Johnson:You do have a dramatic shift in perspective and it's very hard to get into it. It begs a very important philosophical question. Who am I? Yes. if i'm defined by my experiences it roughly equates to my neurons are wired in a way yes 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 yeah 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 yes Are you a different person now? And what does that say about, are we ever a persistent person?

21:37Right? Yeah.

21:38Bryan Johnson:Your question is spot on. Probably the most dramatic reconstruction of your 60 plus trillion cells than anything you can do in life. It may be like a near-death experience would maybe be close, but it's a dramatic rewiring of you as a human. Your values can change too. That's right. 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 that's right i think it's another important question that comes out of all this i agree and like you you know like you now think about that that's through the frame where the world changes at a certain speed.

22:26Bryan Johnson: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 like move with the change yeah and so there's potentially a where it it flips from a liability to an asset where like now i do want that restructure changing even though you have some tail risk of like maybe my priorities will shift 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 the ramifications or the experience and that they wouldn't go through it.

23:22How far would you take it? Would you wire yourself up to a neural link 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? Yes. Yes. Is there a limit to what you would try? Interesting.

23:54Where do you think that comes from?

23:55Bryan Johnson: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. That's really my... Did you always have it? Or are you responding to childhood suppression of those opportunities? It's probably an overcompensation 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. Yeah. And so, yeah, maybe it's probably just I'm now flipped in the opposite.

24:33Bryan Johnson:Yeah. And so, I mean, that's probably true that I really, I don't trust my internal generation of reality. Yeah. You know, I know I'm always making things up. I've got 188 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 a company is 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. Do you find that you've been challenged in maintaining, I would call it external responsibility as you explore and enhance yourself so much?

25:14do you give up the responsibility to others around you who maybe are dependent on you or in need of you?

25:19Bryan Johnson: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 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. 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 5MEO, my partner Kate, like she's got a ton of risk.

26:00Bryan Johnson:Like what if it goes poorly? What if I change my perspectives? What if something bad happens? 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? right? That's right. I mean, that's a consequence, but let's shift topics to other modalities for longevity. Yeah. 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 as interventions, are there other things that are on the horizon that you're either excited about or that you're considering yourself?

26:39Bryan Johnson:Yeah. I mean, two of the ones that we've spoken about, cell therapy and gene therapy, yeah yeah they um 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 um the next gen therapies are just not there yet so we're looking at mitochondrial rejuvenation 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 uh attacked by the immune system exactly which is incredible and i i'm a big big big believer in this this this course of therapy i think it's going to be a whole therapeutic modality that no one has even recognized i agree we have our first uh mitochondrial therapy lined up so how are you going to do it you're you're like 99.9 you need someone who's like 48.7 to try the mitochondrial i agree particularly like you know, I think they tried it in Parkinson's patients, Alzheimer's patients.

27:37That's where you can really see profound shifts in, in certain metrics for you. It's like 99.9 to what? Like, yeah, yeah. I had the mitochondria, you know, of a 48 year old, right?

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27:47Bryan Johnson:So like, what if I, what if I connect? Yes. You could go to your sibling's child because the mitochondria is passed maternally because it's in the, it's in the egg cell. Yeah. So it's the mother's mitochondria. So if you go down in 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 this is a perfect extension i've had a blood boy as a son yeah so now i'm just going to go to the extended family and be like guys it's a it's a family project yeah family project exactly yeah well that one's super interesting and we also have one that we're doing um i've i'm now building 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?

28:32Yeah, a third company.

28:33Bryan Johnson:Yeah, so I'll do a blood draw in the next week or two. They'll spin up and then we'll - They'll do it. Yeah, I'll do it. Okay. Yep. 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. Exactly right. Then you're going to multiply yours out. Yes. And probably select a little bit or - Exactly right. For healthier ones? Exactly right. Right, okay. And then put it back in. it's very i mean exploratively like we don't know uh we're one of the first they're they're in phase two now do you sprint yeah i do so you could probably score if you did it intramuscular like mitochondrial therapy you could sprint to your score that's a great idea yeah thank you yeah yeah that would be a great way to measure it from a rather than just a basic biomarker perspective yeah be really interesting to see yeah sprinting is one of the most underappreciated longevity therapies yeah i i don't do it oh i've got the um the age of a 74 year old uh roughly i am uh 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 in your body and then that gene makes a protein in your body that that does something like the one we were looking at in the foxhole 3 expression yeah exactly so the mesenchymal stem cells it packaged up with the foxhole 3 delivery um yeah that showed that over 50 percent of tissues getting that rejuvenation it's unbelievable unbelievable it's like the unbelievable it's the best demonstration in the entire world that's perfect for tissue regeneration like as a particular application set tissue regeneration using that sort of system seems like a no-brainer it's like yeah it's safe right yeah yeah yes i uh reached out to that chinese professor i'm really interested in seeing it replicating i would love you reached out to the chinese professor yeah it's awesome yeah we sent that paper yeah yeah yeah that's awesome so did he respond uh yeah awesome yeah good uh so we i'd love to do that um i'd love to actually build it ourselves yeah but that's like a two-year project so um ai can help make it fast that's true yeah actually that's true ai as a project manager for these sorts of programs is you know that's true we spoke about this six months ago yeah and things are so different so different now six months later and in terms of stand that up um so that was cool So I think that's a good option.

30:43Bryan Johnson:But also I'm doing Brian Johnson organoids. So we took my iPSCs. We now have them - Induced pluripotent stem cells. Exactly. So you took your cells, turn them into stem cells. Yep. Yeah. 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 dish. So you have a plot. So let me just walk the audience through this. So you take cells off of your skin or something. Blood. 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.

31:12And 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

31:23Bryan Johnson:that you then use for... Like you can say, okay, what if you get Brian Johnson blank drug? What happens? Is it good? Is it bad? What are the side effects? In the Petri dish, you put the drug in there. Exactly. See what happens. Yeah. Okay, got it. You can simulate all these experiments. So now you get the advantage of time of acceleration of like what to take why what dose that's awesome what combatorial things to consider yeah and so we we have the organoids stood up we haven't done our first takes yet yeah 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 yeah totally that's a good one but i mean i don't know we'll see it it's cool in concept i mean tbd if it actually works so yeah see have you tracked any of the alternatives to yamanaka factors the factor discovery work that's going on?

32:11And do you think there's anything worth testing at this stage?

32:13Bryan Johnson:Yeah, I'm an investor new limit. So I've talked to them about the weather at and Blake and Brian's company. They've done. I mean, they've made remarkable progress. Yeah, they figured out how to computationally solve the discovery process. Yeah. And so they, they're much faster than they initially thought. And so that's very encouraging. The big challenge with Yalamanaka 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 yeah 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 yeah 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 yeah that's my theory on where this will end up.

33:06That makes a lot of sense. Any other control mechanism

33:08Bryan Johnson:will be inadequate. That's right. Feedback loop just... All you need is one error and you're in trouble. Yeah. But 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 in what's possible. And in the future, like I think we'll look back and we'll see GLP-1s as the first big drop. Yeah. Like what? I can just inject myself and like it solves hunger. Totally. Yeah. And then the second will probably be something like New Limit or one of these fox one of these plasmin based foxo three therapies where it will show real life like dramatic changes totally and then humanity will shift as like uh longevity being a vision of sci-fi you know rich people pursuit to like something that is truly jamming go back to like the conversation on on the temptation towards socialism right like if if you can feel robust in your ability to pursue life and be healthy and vibrant and in control.

34:05Bryan Johnson:I think these things that have dramatic changes in society, not just in health, but like - 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. 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. I think the happier we will all be with each other. i think like honestly like a lot of the external conflict only comes from internal unhappiness 100 so if you look at the general malaise of like american society like no wonder uh things are right like you've got met 84 of people have metabolic disorder over 40 of people are obese like we're just in really poor health nobody's sleeping everyone's on their phone like 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 decision of you, your community, your country.

34:58Bryan Johnson: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. 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? Yeah. I mean, I guess the question is, I forget on the FOXO3 study, I don't know if they saw brain rejuvenation.

35:29Didn't see that. I did not see that. And I don't, I don't remember. I mean, it is a very complicated organ. Yeah, exactly. And it's insane. It's very hard to reach. 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. yeah because it's never been done before yeah so understanding the consequence of neuro regeneration is like so i'm wondering like if the role in my play like you know maybe psilocybin and 5-mio won't be um you know meaningful for like basic functions of the body

36:08Bryan Johnson:but maybe it's the uh the outperformer in youthfulness 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 totally and maybe that's the role of psychedelics is you but just get a wash of like the snap back of like i can and i can bounce yeah 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 basically like i mean i felt like it was like 30 40 years of psychological rejuvenation like you know it's like to transform me back to a childlike state yeah that is insane i don't get that from the sauna yeah or from eating well or from sleeping well like i'm still right so it's right just unique 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 yeah i'm gonna go to bed on time yeah okay do my wind down routine yeah you do you yeah yeah i appreciate it this has been great brian johnson thank you thanks yeah that was awesome that was great I'm going all in

37:51I'm going all in

From the publisher

(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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