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Full episode · 38 min

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

Bryan Johnson says 5-MeO-DMT produced a profound subjective reset, but its longevity effects and duration still need measurement.

All-In · David Friedberg

The best minutes

  1. 2:025-MeO-DMT felt like a complete release of the ego7 min
  2. 15:58Psychedelic risks depend partly on dose and setting8 min
  3. 26:17Cellular switches may control gene rejuvenation dosing7 min

Also worth watching

  1. 10:34Johnson describes a calmer response to conflict after 5-MeO-DMT2 min
  2. 23:31Johnson links his openness to a rigid religious childhood3 min
  3. 35:05Psychedelics may help preserve a youthful outlook2 min

Skip the roughly two-minute brain-scan methods discussion and the closing exchange about sleep routines.

Summary · 4 min read

Johnson says he began a longevity project five years ago, ranking interventions by published evidence and testing options such as exercise, nutrition, sleep and psilocybin. He says he has used Kernel to measure brain activity and is developing personalized organoids from his induced pluripotent stem cells; he is also an investor in New Limit.

Johnson frames psychedelics as a possible longevity tool after personal observations with psilocybin, and says 5-MeO-DMT produced a stronger subjective reset; he has not yet seen the brain data from that experience. He describes changes in self-talk, mood and relationships, while acknowledging risks of psychosis, bad trips and altered priorities; David Friedberg presses him on those consequences. Johnson also discusses mitochondrial and gene therapies, organoids for drug testing and cell reprogramming, while noting that some work remains experimental. He argues that advances in health and longevity could expand abundance, and sees psychedelics as potentially preserving a youthful outlook.

Minute by minute

  1. 0:43

    Psychedelics entered after evidence review. Johnson says his team began with interventions supported by published evidence, from exercise, nutrition and sleep to sauna and rapamycin. Psychedelics were not initially on the list; mouse findings led them to test psilocybin in three 25-milligram doses, which he says suggested a possible longevity effect.

  2. 2:09

    Johnson describes a profound 5-MeO experience. Johnson says the experience came on within seconds and felt overwhelming and nonvisual. He said it first felt threatening, but surrendering control gave way to bliss, and he called it the most intense experience of his life.

  3. 6:08

    Psychedelics may loosen entrenched brain patterns. Johnson describes the default mode network as supporting self, ego and rumination, with habitual patterns growing stiffer over time. He says Kernel measurements showed that psilocybin weakened familiar activity patterns and that new ones emerged, which he links to neuroplasticity.

  4. 8:57

    Psilocybin findings prompted a 5-MeO test. Johnson says mouse research on psilocybin included reduced inflammation, and that his own tests showed changes in blood glucose and his microbiome. He reports that his blood-glucose percentile shifted from the top 99.5 to the top 99.9 percentile. He says 5-MeO felt like it shut down his default mode network more completely, but describes that as a subjective impression.

  5. 13:46

    5-MeO brain data remain pending. Johnson says he has not yet learned what the 5-MeO brain data show. His team collected structural and functional MRIs, Kernel optical measurements and real-time EEG to examine the brain through several modalities. He contrasts that pending analysis with what he calls dramatic restoration of youthful brain patterns after psilocybin.

  6. 15:58

    Safety depends on careful screening. Friedberg raises the risk of psychosis and lasting harm; Johnson agrees that bad trips and unsuitable candidates are real concerns. Johnson argues that dose, setting and supervision are often poorly controlled, and says use should involve licensed professionals and careful screening. He does not claim that safeguards remove all risk.

  7. 18:30

    Perspective shifts can disrupt commitments. Friedberg says he has seen people leave companies and relationships after psychedelics, and notes that some investors have tried to restrict founders from using them. Johnson says he knows this happens, but his own experience made him more committed to his work; he agrees that psychedelics can sharply change perspective.

  8. 20:51

    Fast change may reward flexibility. Johnson agrees that psychedelics can rewire identity and values, and says psychological flexibility may help people adapt as AI accelerates change. He says he would consider neural implants and gene-expression interventions, tracing his appetite for experimentation to a highly structured religious childhood. He says fatherhood remains central and his commitment to his three children has not changed.

  9. 26:17

    Mitochondrial therapy remains exploratory. Johnson says a first mitochondrial treatment is lined up with a third-party company, with a blood draw planned in the next week or two. He and Friedberg discuss growing mitochondria from a young maternal-line relative as a possible biological match, but Johnson describes the work as exploratory.

  10. 29:31

    Friedberg cites a FOXO3 tissue result. Friedberg points to a paper on FOXO3 delivery in mesenchymal stem cells and says it reported rejuvenation in over 50 percent of tissues. Johnson says he contacted the Chinese professor behind it and is interested in replication, though building the system himself could take two years.

  11. 30:34

    Organoids could screen drugs before use. Johnson says his team turned induced pluripotent stem cells into heart, liver and lung organoids to test compounds in a dish before trying them in his body. He says they have not run their first tests, so the approach remains unproven.

  12. 31:58

    Cell reprogramming needs precise controls. Johnson, an investor in New Limit, says the company has made computational progress on factor discovery and is moving faster than expected. He notes that excessive Yamanaka-factor dosing can make a cell cancerous, and says he thinks cellular switches could regulate protein production more precisely.

  13. 33:16

    Abundance could improve social well-being. Johnson argues that GLP-1s may be the first major step toward broader longevity therapies, with gene- and plasmid-based approaches following. He and Friedberg argue that greater abundance in food, energy, housing, mobility and lifespan could improve social well-being. Johnson links poor health to social malaise.

  14. 35:05

    Psychedelics may restore youthful outlook. Johnson says tissue regeneration does not answer how changes to the brain might affect identity. He suggests psychedelics may matter less for basic bodily functions than for maintaining a youthful disposition, and says 5-MeO felt like decades of psychological rejuvenation, unlike sauna or eating well.

Published Mar 26, 2026.

Transcript · 31 min read

All-In, hosted by David Friedberg, with Bryan Johnson.

Transcribed by machine (Whisper) from the episode’s audio, so a word may be off here and there.

  1. 0:00

    Bryan Johnson, thanks for being here. 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. you know what many of the biggest tech ceos and vcs have in common they sleep on the pod by eight sleep 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 eightsleep.com slash all in and use code all in for up to $350 off your pod purchase today.

  2. 0:54

    Before we get into your experience, why did you choose to do it? Two things. 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, you know, being used in ritualistic practices or being pointed at things like depression and anxiety and in certain trials, 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 uh 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 it's yeah it's a clinical uh dose very very close to a hero dose and we found that we think it's a longevity therapy let's get to

  3. 2:08

    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 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 hits 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 every very little

Read the whole transcript
  1. 3:41

    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 That the stream of existence is going to just tear you to shreds. It's going to shard you. And if you give up. Like break your brain. Yeah. You feel like it's going to like threaten your sanity. Like is it going to chop you up into little pieces? And so in that moment, you have to say, do I try to wrestle this and I need to just like wait it out until it's over or you just relent. You say yes.

  2. 4:26

    and you have to in that moment you have to say yes so thoroughly you have to release all

  3. 4:33

    Bryan Johnsonattachment 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. 4:51

    and i i again this like a v1 of trying to explain this but if i list out the the most 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 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 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 you're in the depths of existence like this it's just the most majestic 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 i mean like it um i mean one it completely dissolves your default mode network describe what that is so like um it's this is the engine that constructs

  5. 6:31

    self and ego and so as you ruminate you know like you're going through thinking through your day what's next exactly how am i feeling yeah what should i be doing right now constant conversation 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. 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.

  6. 7:04

    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. And we could pick this up with kernel, the brain interface. You can see how the default mode network weakens. So basically, I 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, you know, 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. 7:51

    And then over time... The neurons don't physically move, but the activity shifts around. Exactly. 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 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 so 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 and then that trauma and that anxiety feels like it dissolves or melts away is that a there exactly right yeah yeah and so this is this has been documented in psilocybin it's kind of

  8. 8:56

    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 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 had we found a first in human observation it had this this uh metabolic reset in the brain where my blood glucose before this was in the top 99.5 percentile of all the population okay after it went to the top 99.9 percentile like to move my blood glucose from that level is very very hard but basically like uh 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 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

  9. 10:08

    potential there's some animal evidence um 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 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 it just doesn't run the same way 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 i 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 right and so you are restored to this childlike state and i mean the past couple days uh 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

  10. 11:26

    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 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.

  11. 12:05

    But then adults take that and they like package it up and like they wanna weaponize it and be like, I got something on you and I'm like, move it. I'm gonna 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 just felt absolutely

  12. 12:24

    Bryan Johnsonlike no need to escalate or to defend or to like it was just easy and um it was a breakthrough in

  13. 12:34

    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 I did ketamine at Kernel. So one of our first studies at Kernel is we said ketamine was an 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. And it had some kind of transit effect, but that's like a little league relative to 5-MO. And so as you've gone through this,

  14. 13:49

    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 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 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

  15. 14:58

    mapped the brain over time what did you learn there dramatic uh restoration of youthful brain patterns yeah right yeah and what comes after 5meo like 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 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 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. 16:04

    There's some arguments to be made that psychedelics can induce permanent psychoses, cause functional changes and drive some people that might be predisposed into schizophrenic states. 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. 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 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

  17. 17:18

    the benefits people want without with, you know, with less of the risk, but definitely I agree to 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. 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 i meant 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 you when you sleep well you feel great you exercise great but like nothing like what 5meo did in terms of of like the reset of me as a human so let's just talk about the consequences

  18. 18:37

    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. In the wake of that, there are people that feel they're a victim of that behavioral shift, the investors in the company, I mean, the employees, the family members, et cetera.

  19. 19:23

    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. 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 gonna 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 uh 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, then you lose the founder. Like they're off. Everyone's high and dry. And so they were telling me that they put into deal docs that they can't do this for the duration of the company. 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.

  20. 20:30

    It's not quantified, it's not set in setting. So it's a different thing. But I will say like, I guess me as a person, what I'm trying to focus on,

  21. 20:38

    Bryan JohnsonI came back even more motivated to do what I'm doing now. I don't have a desire to go off in the woods and live that kind of life.

  22. 20:50

    It emboldened me to work on these things, but no question about it, you do have a dramatic shift in perspective and it's very hard to get into it. 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 yeah right 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 it may be like a near-death experience you know would maybe uh 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

  23. 22:15

    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 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 yeah and so there's potentially a where it 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 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

  24. 23:28

    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 can rewire you as a different person yes yes is there a limit to what you would try no interesting where do you think that comes from i think i 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...

  25. 24:09

    Did you always have it? Or are you responding to childhood suppression of those opportunities?

  26. 24:15

    Bryan JohnsonIt's probably an overcompensation of trauma response, like most things are. And so, as a child, I lived in a very structured religious environment where things were cemented.

  27. 24:24

    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 yeah and so i mean that's like probably true that i really uh i don't trust my internal generation of reality 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 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?

  28. 25:00

    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? Do you give up the responsibility to others around you who maybe are dependent on you or in need of you? yeah i have three kids and so um 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 uh 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 yeah 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 well one could make an argument that taking that degree of risk or something could have gone wrong wrong the people around you are enabling versus being supportive right that's right I mean yeah

  29. 26:14

    that's a consequence but let's shift topics to other uh 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 yeah that you're either excited about or that you're considering yourself 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 coded the mitochondria in effectively a red blood cell envelope, which made it more transportable into cells and less attacked by the immune system.

  30. 27:13

    Yeah, exactly. Which is incredible. And I'm a big, big, big believer in this course of therapy. I mean, it's gonna be a whole therapeutic modality that no one has even recognized. I agree. We have our first mitochondrial therapy lined up. So how are you gonna do it? You're like 99.9%. You need someone who's like 48.7% to try the mitochondrial, particularly like, you know, I think they tried it in Parkinson's patients, Alzheimer's patients. That'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? So like, what, 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 to In the mother's line maternally, if you have a sister who has a kid, they're going to have very young mitochondria.

  31. 28:06

    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 family project. Yeah, family project. Yeah, exactly. Yeah. Well, that one's super interesting. We also have one that we're doing. I'm now building. sorry are you going to do your own mitochondrial transplantation you're going to build a bioreactor are you using working with one of the third parties yeah a third company yeah so i'll get i'll do a blood draw in the next week or two they'll spin up and they'll do it yeah 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 then you're going to multiply yours out yes and probably select a little bit or exactly healthier ones yeah right okay and then so 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

  32. 29:08

    it intramuscular like mitochondrial therapy you could sprint 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 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 you know 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 it's like yeah yes i uh reached out to that chinese professor i'm really interested in seeing

  33. 30:11

    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 good option but also i'm doing uh brian johnson organoids so uh we took my ipsb ipscs we now have 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 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 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 yeah and then you put other

  34. 31:13

    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 yes that you then use for like you can say okay uh 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 in the petri dish you put the drug in there exactly see what happens yeah okay 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 that's awesome what combinatorial 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.

  35. 31:59

    Totally. 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. 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? Yeah. I'm an investor in New Limit. So I've talked to them about where they're at. Blake and Brian's company. They've done, I mean, they've made remarkable progress. They figured out how to computationally solve the discovery process. yeah and so they um they're much faster than they initially thought and so that's very encouraging you know the big challenge with young monaca 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

  36. 32:53

    Bryan Johnsonthat 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

  37. 33:02

    of gene expression in the cell. That's my theory on where this will end up. That makes a lot of sense. Any other control mechanism will be inadequate. That's right. All you need is one error and you're in trouble. 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. in the future like i think we'll look back and we'll see glp ones as the first big drop yeah like what i can just inject myself and like it solves hunger and totally yeah and then the second will probably be something like new limit or one of these fox one of these plasmid based 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 uh in control 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 and housing in

  38. 34:13

    mobility and lifespan the more abundance people get the happier they are yes and the more you're improving abundance in the world the the better we are going to live as a group of people together on planet earth exactly yeah 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 percent of people have metabolic disorder over 40 percent 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 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

  39. 35:17

    with psychedelics? Like, are they as profound? 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. 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. 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 the neurons back maybe in the wrong way or 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 wonder like if the role in that play like you know maybe

  40. 36:00

    Bryan JohnsonPsilocybin and 5-MeO won't be meaningful for basic functions of the body, but maybe it's the outperformer in youthfulness of your disposition towards reality.

  41. 36:18

    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 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 Like I'm still, so it's just unique.

  42. 37:18

    Yeah. Amazing. Well, listen, I'm going to go drink alcohol and eat carbs and stay out late. I don't know. What are you going to do? Yeah. I'm going to go to bed on time. Yeah. Okay. I'm going to do my wind-down routine. Yeah. You do you. Yeah. You as well. Enjoy it. I appreciate it. This has been great. Bryan Johnson. Thank you. Thanks. Yeah. That was awesome. That was great. I'm going all in. I'm going all in

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