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All-In · · 38 分钟

Bryan Johnson:我刚服用了全世界最强的一剂 DMT……这是我的体验

David FriedbergBryan Johnson

YouTube
TL;DR
  • Johnson的核心判断是,迷幻剂可能通过打破因年龄而僵化的大脑模式,成为一种长寿疗法;而饮食、运动、睡眠、桑拿和高压氧做不到这一点。 服用5-MeO-DMT 48小时后,他称这是“作为一个人的我被重置了”(“reset of me as a human”),但目前只有主观感受;结构 MRI、功能 MRI、Kernel 成像和 EEG 分析仍在等待结果。

  • 他此前的裸盖菇素实验提供的是假设,而非证据:3次25 mg剂量似乎削弱了惯常连接,让他的血糖排名从全人群前99.5%升至前99.9%,并改变了微生物组。 Johnson将这些观察与小鼠证据及炎症减少联系起来,称“我们认为这是一种长寿疗法”;因果性、持久性和可推广性仍未解决。

  • Johnson的描述显示,5-MeO的急性体验在强度上完全不在一个量级:10秒内起效,几乎没有视觉内容,并似乎将构建“自我”和“自我意识”的默认模式网络这台“引擎”彻底抹掉。 放下“所有执着、所有前提、所有想要和所有欲望”,打开了他所称的最具生命力的人类体验;随后是孩童般的兴奋感、幽默感,以及与伴侣发生冲突时更少防御性。

  • 代价不是单纯的临床风险,而是进入治理层面的风险:Friedberg提到永久性精神病、精神分裂症风险、糟糕的体验,以及创始人在价值观剧变后抛下公司或家庭。 Johnson承认,投资者已经把禁止迷幻剂的条款写入交易文件;量化给药、持牌专业人士监督以及恰当的心理准备和环境或许能降低风险,但“有些人可能就是不适合的候选者”。

  • 这场对话提出了一个问题:随着 AI 加快变化速度,快速重塑心理究竟会从负债翻成资产,还是相反。 Friedberg认为迷幻剂可能帮助人类适应变化,Johnson则称这种状态具有深度的心理灵活性;同一机制也带来尾部风险——身份、优先级和责任都可能改变。Johnson说自己回来后反而更投入工作,也更坚定地履行父亲责任。

  • 长寿研发管线远不止迷幻剂,还包括线粒体增强、FOXO3递送、个性化类器官和计算驱动的细胞重编程。 Johnson计划接受一次探索性线粒体治疗,希望复现一项据称由FOXO3实现组织再生的结果,并已用自己的诱导多能干细胞培育出心脏、肝脏和肺类器官——不过测试尚未开始,他反复强调这些概念仍是 TBD。

  • Johnson认为,GLP-1是长寿领域第一个大的“落地节点”,而 NewLimit 或基于血浆的 FOXO3 类疗法,可能在更晚阶段提供一个看得见的验证节点。 真正的瓶颈在控制:Friedberg警告,即使只让1个细胞暴露于过量的 Yamanaka 因子,也可能启动肿瘤;他推测,或许需要由反馈控制的细胞开关来实现这一点。

摘要 · 为研究而整理的核心内容

1. 5-MeO在数秒内带来主观重置

  • 实验结束两天后,Johnson说5-MeO-DMT——按他的说法,强度介于DMT的5到10倍之间——让他“震惊到说不出话”。他接受了9 mg肌内注射,另吸入汽化的7.18 mg;大约10秒内,“人就直接没了”。

  • 与视觉内容丰富的DMT体验不同,这次体验“视觉内容非常、非常少”。Johnson描述说,自己是在近乎无限的尺度上直面“原始意识与原始智能”,同时担心存在本身会“把你撕成碎片”,或让他失去理智。

  • 决定性分岔在于抵抗还是臣服:他说,自己可以选择与体验搏斗、等它过去,也可以放下自我、自我意识、欲望和一切预设。彻底臣服后,他进入了“无法想象的幸福与欣快”,并将其排在成就、婚姻、生育和克服苦难之上。

  • 对他的影响落在一些日常却异常鲜明的细节上:在梦里笑醒,醒来时带着孩子般的期待,脱口而出各种俏皮话;与伴侣Kate发生冲突时,不再防御、不升级矛盾,也不为日后积攒攻击材料。但他仍追问了最关键的问题:“它能持续多久?衰减曲线是什么样?”30天或60天后,从前那个Bryan会不会回来?

2. 长寿假说建立在具有启发性的裸盖菇素信号之上

  • Johnson的5年计划最初按公开研究证据和效应大小对干预措施排序:运动、营养和睡眠排在最前,随后是桑拿、高压氧、雷帕霉素和二甲双胍。团队看到小鼠研究中的裸盖菇素临床前证据后,迷幻剂才进入清单,其中包括炎症水平下降——这是长寿疗法反复出现的特征。

  • 随后,他完成了3次25 mg裸盖菇素给药,同时由Kernel测量脑部活动。Johnson用机场作比喻:普通大脑会维持纽约—伦敦这类高频航线;裸盖菇素相当于把机场拎起来、重新安排交通,压低既有连接,让新的连接得以形成。Friedberg补充说,新连接可能带来新的行为,Johnson回应:“完全正确。”

  • Johnson称自己的代谢状态发生了重置:血糖指标从全人群前99.5%升至前99.9%,微生物组发生变化;他还说,Kernel显示其大脑模式出现了显著的年轻化恢复。但对5-MeO而言,诚实的结果是“到目前为止,什么都没有”:结构 MRI、功能 MRI、Kernel 光学测量和实时 EEG 都已采集,但尚未完成分析。

3. 更好的心理准备和环境也无法消除临床与创始人风险

  • Friedberg明确提出临床层面的反驳:迷幻剂可能让部分使用者留下心理创伤,诱发永久性精神病,或将有易感性的人推向精神分裂症。Johnson承认,这种风险“并非零概率”,糟糕的体验也可能给人留下长期创伤;Friedberg表示,这些化合物值得最高等级的谨慎。

  • Johnson认为,随意食用蘑菇往往叠加了菌种不明、裸盖菇素剂量不明、心理准备和环境糟糕、无人监督等问题。定量给药、持牌专业人士、合适的心理准备和环境,以及排除不适合的候选者,或许可以搭建更安全的框架,但他强调,相当一部分风险仍然存在。

  • Friedberg随后将讨论从患者风险推向交易对手风险:他听说过一些 CEO 在迷幻剂体验后彻底放弃公司和家庭,让投资者和员工“彻底失去依靠”。Johnson也听说过投资者在合同中禁止创始人在公司存续期间接触迷幻剂;但他自己的结果恰恰相反——动力更强,没有躲进森林、彻底消失的念头。

  • 更深层的问题是,一个人的神经回路被重编程后,他是否还是同一个人,尤其是在价值观和责任都可能改变的情况下。Johnson说父亲身份依然是他生活的核心,但接受了Friedberg对“支持”和“助长”的区分。当被问及神经植入物、转基因质粒,以及自己是否存在最终的实验边界时,Friedberg对前两项技术都回答“是”,对是否存在边界回答“否”。

4. 下一层长寿技术栈进入细胞、基因与类器官

  • 在基本做完今天可用的干预项目后,Johnson正在等待细胞和基因疗法。他眼下最近的一项实验是线粒体增强:第三方将抽取血液,从生物学匹配来源扩增线粒体,再通过探索性手术回输。Johnson说,自己会在1到2周内完成抽血;Friedberg则称,这项疗法已处于2期。

  • Friedberg建议采用肌内递送,并以短跑表现作为功能性读数,Johnson当即称这是个好主意。

  • 两人还讨论了一种据报道利用间充质干细胞递送FOXO3的系统。Johnson说,该系统在超过50%的组织中显示出年轻化效果;他已联系参与这项工作的中国教授,希望复现结果,或者在内部重新搭建一套系统。项目原本预计耗时2年,但两人都认为,AI现在可能压缩前期搭建周期。

  • Johnson还将自己的细胞重编程为诱导多能干细胞,并培育出心脏、肝脏和肺类器官。目标是在让身体接触这些分子之前,先在培养皿中测试不同分子、组合和剂量,以争取时间并筛查并发症。Johnson说首轮测试尚未开始;Friedberg称这一概念很有吸引力,但能否奏效仍是 TBD。

  • 作为NewLimit的投资者,Johnson说,计算发现细胞重编程因子的进展快于预期。Friedberg认为,剂量控制是生死级瓶颈:哪怕只有1个细胞剂量过高,也可能变成癌细胞并迅速长成肿瘤。他推测,细胞内或许需要一种反馈开关,能够测量基因表达,并将蛋白质合成打开或关闭;Johnson表示认同。

5. 心理年轻化可能是迷幻剂的差异化应用场景

  • Johnson说,迷幻剂对基础身体功能未必有多大意义;它的细分价值可能在于恢复一种年轻化的现实心态:野心、好奇心,以及一切皆有可能的感觉。他形容5-MeO带来了“30或40年的心理 rejuvenation”,像是一次瞬间弹回,而睡眠、饮食和桑拿从未产生过这种效果。

  • Friedberg提出,在 AI 加速的世界里,人类能否足够快地改变自己,并认为迷幻剂可能成为适应变化的盟友。Johnson称Friedberg对这类变化的开放态度体现出“深度心理灵活性”(profound psychoflexibility);但讨论也保留了尾部风险:人格和优先级可能随之改变。

  • Johnson另行提出,食物、能源、住房、出行乃至生命本身变得充裕,会改善整体福祉。Friedberg随后援引数据称,84%的人存在代谢问题,超过40%的人肥胖,同时还面临睡眠质量差、手机依赖和心理健康问题。在Friedberg看来,更好的健康状况或许能重新激活集体的“想做就能做”心态。

David Friedberg

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.

Bryan Johnson

Yeah, I did 5-MeO-DMT, which is the most powerful psychedelic on the planet—somewhere between 5 and 10 times more powerful than DMT. It’s been 48 hours, and I’m still learning how to talk about it.

David Friedberg

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

Bryan Johnson

Two things. One, mostly as a longevity experiment. When I started this project 5 years ago, the approach we had was to go through all of the scientific evidence ever published on health and longevity and try to find the interventions that have the best evidence for effect size. We just went down the list, from the top-performing interventions on down.

Of course, you start with exercise, nutrition, and sleep. You work your way down to things like hyperbaric oxygen therapy and sauna, and then rapamycin and metformin. We never actually had psychedelics on our radar. They were always either an ancient medicine being used in ritualistic practices or being studied for things like depression and anxiety, but they were never understood as a rejuvenation protocol—something that was for anti-aging.

Then we found some preclinical evidence in mice on psilocybin and thought, “That’s interesting.” We did the world’s most studied, most quantified experiment with psilocybin: 3 doses at 25 milligrams of psilocybin, which is a pretty high dose. It’s a clinical dose, very close to a hero dose. We found that we think it’s a longevity therapy.

David Friedberg

Let’s get to that data in a minute. But then you decided to try 5-MeO this weekend?

Bryan Johnson

Yes.

David Friedberg

Walk me through the experience, because you televised the whole thing. It was livestreamed. You looked amazingly calm going into it and throughout the process. Walk us through your experience.

Bryan Johnson

I think those who have done 5-MeO would probably relate with me that it feels like an impossible task to explain what it’s like. With that caveat, I’ll give it a go.

I’m stunned—absolutely floored, speechless. You basically experience raw consciousness and raw intelligence. Whatever these words convey to you, take that idea, multiply it by 1,000, and then expand it out to infinite depth, infinite width, and infinite dimensions. That gives you a rough map of the size and space that you deal with.

It was incredibly hard because you get blasted into this space that is so foreign, you don’t even know what’s happening. It happens very quickly. You inhale it. I did 9 milligrams intramuscularly and then 7.18 milligrams vaporized, and it takes you within 10 seconds. You’re just out.

David Friedberg

Visual changes?

Bryan Johnson

Very, very little visual change. With DMT, it’s a very visual experience. You’ll meet the elves or whatever else. This is not a visual experience.

You get into this world and lock into one of two states. You either panic because you feel like the gates of hell are going to open, that the stream of existence is going to tear you to shreds, that it’s going to shard you.

David Friedberg

Like breaking your brain?

Bryan Johnson

Yeah. You feel like it’s going to threaten your sanity. Is it going to chop you up into little pieces? In that moment, you have to say, “Do I try to wrestle this and wait it out until it’s over, or do I just relent and say yes?”

You have to say yes so thoroughly. You have to release all attachment, all preconditions, all want, and all desire. You have to release self, ego, and control. You just have to relent entirely. When you do that, it opens up this unimaginable bliss and euphoria.

Again, this is a V1 of trying to explain it, but if I list out the most dynamic experiences I’ve had as a human—certain accomplishments, getting married, having a child, overcoming a difficulty, or whatever you list—this is, without question, the most dynamic experience I’ve ever had as a human.

David Friedberg

Does the internal chatter, the internal monologue of the ego, turn off?

Bryan Johnson

It does.

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?

Bryan Johnson

It’s a visceral feeling. You’re hyper-aware of what’s happening. When you take a very high dose, you don’t really know what’s happening in the first few minutes, but then you come to and you’re hyper-aware of everything.

It’s not visual, but you’re in the depths of existence. It’s just the most majestic experience achievable by a human—by intelligent life. I can’t imagine anything more miraculous.

David Friedberg

You’ve studied the biology and the biochemistry. What goes on in the brain as this molecule hits your neurons?

Bryan Johnson

It completely dissolves your default mode network.

David Friedberg

Describe what that is.

Bryan Johnson

It’s the engine that constructs self and ego. As you ruminate, you’re thinking through your day: What’s next? How am I feeling? What should I be doing right now? It’s a constant conversation.

“Do I feel bad about myself? Do I feel shy? Do I feel bad about whatever?” You’re doing this rumination stuff. Kids don’t have this rumination loop. Their default mode network is quiet.

As you age, you build up this default mode network into stiffer patterns. Your experience of reality becomes increasingly narrow. You have these big ruts that form. You can see people in their patterns, just as you can see how open a child is to saying very random things. As adults, you’re shut in.

When I did psilocybin, one of the reasons we did it is because it has this effect where it dampens the default mode network. We could pick this up with Kernel, the brain interface. You can see how the default mode network weakens.

I think of the brain like a globe with airports scattered about. You have certain traffic patterns, like New York to London, with a certain number of flights every day. That’s a very strong connection. But New York to some small town in Arkansas has a very low-traffic map.

When you do something like psilocybin, it basically takes the airports, picks them up, and repositions them in the world so they’re all scrambled. The traffic patterns aren’t the same. Over time—

David Friedberg

They don’t physically move, but the activity shifts around.

Bryan Johnson

Exactly.

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, allows new behaviors and new ways of thinking to emerge.

Bryan Johnson

Exactly.

David Friedberg

Coming out of these therapeutics, is that a fair way to describe it?

Bryan Johnson

Exactly right. You look at my brain on psilocybin from Kernel, and you see my patterns before, like the New York-to-London connection. You see my brain afterward, and it’s exactly what you said: new patterns are emerging, and the old ones have quieted down. It’s like a new map of connectivity. We saw that happen, and it does generate a lot of neuroplasticity.

David Friedberg

Obviously, this neuroplasticity—rewiring these connections in the brain—is what allows trauma victims, or folks who have a certain wiring that they keep repeating in their brain, which causes trauma and anxiety in their lives, to get rewired. Then that trauma and anxiety feels like it dissolves or melts away. Is that a fair way to describe it?

Bryan Johnson

Yeah. This has been documented with psilocybin. It’s fairly well understood.

David Friedberg

How did you connect that psilocybin data to an effort in longevity? Was this just a random idea—“Let’s try it out”?

Bryan Johnson

We saw some mouse data showing that it had these effects. It also showed reduced inflammation. We said, “This is interesting,” because most longevity therapies do something with inflammation, right? Inflammation is the killer. If you can lower inflammation, it’s a very good sign.

If you can do something that makes the brain more youthful and takes down those big ruts, that’s also useful. What we found with psilocybin was a first-in-human observation: it had a metabolic reset in the brain. My blood glucose before this was in the top 99.5% of the population. Afterward, it went to the top 99.9%.

To move my blood glucose from that level is very, very hard. It wasn’t like metformin, where you’re doing something to blood glucose. This just had a reset across the body. It also changed my microbiome, so we saw full-on effects.

Then we said, “Okay, if that had that consequence, 5-MeO may have some similar characteristics.”

David Friedberg

No one had done this with 5-MeO before?

Bryan Johnson

Exactly. There’s potential. There’s actually some animal evidence. The similar dynamic is: Can you take the brain and basically smooth out the barnacles that accumulate?

5-MeO-DMT, compared to psilocybin, absolutely blasted my default mode network clean.

It felt like psilocybin dampens it. It softens it, but this thing just annihilated my default mode network.

David Friedberg

Turned it off completely.

Bryan Johnson

Yeah. It just doesn’t run the same way. For example, 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.

After I woke up, I thought, “That’s really weird. I don’t remember laughing.” I looked it up, and apparently that’s characteristic of a child.

David Friedberg

Right. So, you are restored to this childlike state.

Bryan Johnson

The past couple of days, I have felt childlike. Yesterday morning, I felt that emergent excitement—the bubbling feeling of, “Today is so exciting. I’m going to do new things. I’m going to have new experiences.” You’re just excited about everything.

I haven’t felt that in so many years. It really was profound on every layer. I feel like I’m stumbling through it because I don’t even know how to talk about it.

David Friedberg

During the day, when you’re hanging out and walking around, is your brain having the same normal chatter that it did before, or do you think there’s a persistent change in that default mode network?

Bryan Johnson

Yeah, definitely a change. I was with my partner, Kate, yesterday, and I did something that made her upset. In that situation, when couples are in that moment, you have this negotiation: How do I sort this out?

It all became so clear to me. When children have a fight, they have it out, and then it’s done. They move on. But adults take that, package it up, and weaponize it: “I’ve got something on you. I’m going to move the chess pieces and try to leverage this.”

Or they store it up like a snake in one of those things that pops out all the things later.

David Friedberg

[laughter]

David Friedberg

It’s like they package it all up.

Bryan Johnson

Exactly. We had this situation, and I felt absolutely no need to escalate, defend, or do anything. It was just easy.

David Friedberg

Easy.

Bryan Johnson

It was a breakthrough in our relationship, where I was able to communicate with her in a different way.

It’s like laughing in my sleep. It’s how I deal with my partner. When I walk around, I just feel so much funnier. My ability to make immediate quips has changed.

I feel renewed as a person in a way that I really didn’t imagine.

David Friedberg

Have you tried hallucinogens before you started your longevity path a couple of years ago?

Bryan Johnson

Yeah.

David Friedberg

Did you do that recreationally or therapeutically?

Bryan Johnson

It was mostly therapeutic. I had sold my company, Nootrobox, gotten a divorce, and left the Mormon Church. I was trying to remap my life: What is life? Who am I? What do I do?

I was in that rebuilding stage, where I dabbled. I did ketamine at Kernel. One of our first studies at Kernel asked, “What happens when you do ketamine?” Ketamine was an up-and-coming therapy for depression, so we conducted the world’s most extensive measurement of ketamine with Kernel, before, during, and after.

It was interesting, and it had some kind of transient effect, but that’s a Little League relative to 5-MeO.

David Friedberg

As you’ve gone through this, maybe share a little bit of the MRI data you’re gathering and the other data mapping the neurological effects. Tell us a little bit about what you’ve learned so far.

Bryan Johnson

So far, nothing. I have my subjective experience to share, but we have a structural brain MRI, a functional brain MRI, the Kernel optical interface, and real-time EEG capture.

We should talk about the different modalities because I think it’s important. Structurally, you can see the physical brain. Functionally, you can see the activity in the brain—neurons firing and neurons that are not firing—and then electrical activity measured by an electrical device.

We basically wanted to look at the brain through every modality possible because the brain is very hard to rejuvenate. We’ve had a lot of success rejuvenating my heart, lungs, muscles, and body fat, but rejuvenating the brain is very hard.

This is why this is such a promising therapy. We wanted to look at blood flow, structure, molecular changes, and waveform patterns. It’s a very high-fidelity quantification, so we’ll see what the data shows. I’m very excited.

David Friedberg

Right. This on psilocybin as well, right? You mapped the brain over time. What did you learn there?

Bryan Johnson

Dramatic restoration of youthful brain patterns.

David Friedberg

Yeah, right. And what comes after 5-MeO?

Bryan Johnson

[laughter]

David Friedberg

How far do you take this?

Bryan Johnson

Honestly, I am so encouraged by psychedelics. In the community where I spend time, psychedelics have always been understood as a retreat or a ritual you go to for various explorations, but never in the world of longevity. They’ve never been understood as that thing.

Now, after seeing the data, I’m more interested than ever. Of course, you have to be very careful when talking about psychedelics because they’re extremely powerful. It’s not, “Go out and do them, everybody.” They need to be done properly with a licensed professional and carefully. The person needs to be in the right state. They are not to be taken lightly.

I am more interested than ever in psychedelic compounds. They’re uniquely powerful.

David Friedberg

There are some arguments to be made that psychedelics can induce permanent psychoses.

Bryan Johnson

Yeah.

David Friedberg

They can cause functional changes and drive some people who might be predisposed into schizophrenic states.

Bryan Johnson

That’s right.

David Friedberg

How did you get over those risks? For a lot of people, that would turn them off from trying psychedelics.

Bryan Johnson

Yes. It’s not a nonzero percentage of people who suffer these consequences.

David Friedberg

Yeah, I agree.

Bryan Johnson

There are also people who have really bad trips that leave them scarred. Part of what could be contributing to this is that people, for example, try magic mushrooms in a social situation. Someone’s got a bag, they pull out the mushrooms, and it’s like, “Yeah, it weighs blank,” so they pop one in.

But they have no idea what kind of mushroom strain they’re eating. They don’t know what the dose of psilocybin is. It’s unquantified and unsupervised, with the wrong set and setting.

Much of the risk persists, but I don’t think we’ve approached psychedelics with the appropriate rigor to make them as safe as they should be. That’s not to say we can solve the safety issues for everyone. Some people may simply not be appropriate candidates.

But if we create a safety structure around them, they could deliver the benefits people want with less risk. I agree with you: they deserve all the caution in the world.

David Friedberg

You can get neurogenesis, neuroplasticity, and trauma resolution. How is this going to be allowed to become a medical therapeutic that can be more broadly trialed, and eventually brought to people without carrying all the risks and burdens that it does today?

Bryan Johnson

If I subjectively compare my experience with 5-MeO to having a better diet, exercising every day, sleeping well, doing the sauna, and doing hyperbaric oxygen therapy, this was more efficacious than all of them in terms of resetting me as a human. It’s incomparable.

I’m left pondering how long it will last. What is the decay curve? Will I find that I become the former Bryan within 30 or 60 days? Do I have to repeat the cycle? I don’t know.

When you sleep well, you feel great. When you exercise, you feel great. But nothing compares to what 5-MeO did in terms of resetting me as a human.

David Friedberg

Let’s talk about the consequences outside of the physiological, which is life. There are lots of stories of friends and people I know who have tried a heavy psychedelic, like ayahuasca. They were the CEO of a company, and then they quit their company and went off to the jungle, left their family, divorced their partner, or made other dramatic life changes because their perspective had shifted so much.

They reevaluated what mattered in life to such a degree that they gave up many of the things that had mattered before.

Bryan Johnson

Yeah. In the wake of that, there are people who feel they’re victims of that behavioral shift—the investors in the company, the employees, the family members, and so on.

David Friedberg

Can you talk a little bit about those broad risks? We’ve seen it, and I don’t know if you’ve seen the same thing. Friends have said, “I have this new perspective. I’m giving up my life.”

Bryan Johnson

No, I just spoke because I’ve been doing this. People bring this up as a topic of conversation.

David Friedberg

Right.

Bryan Johnson

They say, “I see you’re doing this for longevity, but I’ve seen so many examples where people put money in and you lose the founder. They’re off, and everyone’s high and dry.”

David Friedberg

In your deal—in an investment in you?

Bryan Johnson

No. I just spoke because I’ve been doing this. People bring this up as a topic of conversation. They say, “I see you’re doing this for longevity, but I’ve seen so many examples where people put money in and you lose the founder. They’re off, and everyone’s high and dry.”

They were telling me that they put into the deal docs that they can't do this for the duration of the company. So it is a thing. I have nothing to say about it other than I know it happens.

I would say that most people in the tech world that I'm familiar with have done this in retreat centers or social environments. It's not quantified. It's not set and setting, so it's a different thing. But I will say that, as a person, what I'm trying to focus on is that 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 and live that kind of life. It emboldened me to work on these things, but no question about it, you do have a dramatic shift in perspective. It's very hard to get away from.

David Friedberg

A very important philosophical question: Who am I? If I'm defined by my experiences, it roughly equates to my neurons being wired in a way that's a consequence of my experiences. If I go in and take a drug and, in a few hours, rewire all my neurons, am I the same person? What makes Bryan Bryan?

You can maybe recall some memories of Bryan prior to taking the psychedelic, but Bryan as a person has been rewired. Are you a different person now? And what does that say about—are we ever a persistent person?

Bryan Johnson

Yeah. Right? Yeah, your question is spot on. It's probably the most dramatic reconstruction of your 60-plus trillion cells than anything else you can do in life. Maybe a near-death experience would be close, but it's a dramatic rewiring of you as a human.

David Friedberg

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?

Bryan Johnson

That's right. I think it's another important question that comes out of all this.

David Friedberg

Now think about that within the frame where the world changes at a certain speed. Take the world where it's changing faster. We now know that it's hard to predict what's going to happen 2 weeks from now or a month from now. Things are changing very quickly.

So now you come up with this practical question: Can humans change fast enough in a world where AI is the dominant engine of innovation? In that case, you may want psychedelics as your ally to say, "As a human, I'm struggling to move with the change." So there's potentially a world where it flips from a liability to an asset, where now I do want that restructuring and changing, even though you have some tail risk of maybe my priorities shifting.

Bryan Johnson

You have profound, what I would call, psychoflexibility. I think most people don't. They either have a disinterest in changing who they are overnight, or they're fearful of the ramifications or the experience, and 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?

David Friedberg

Yes, I would.

Bryan Johnson

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 in cells in your body, and basically rewire you as a different person?

David Friedberg

Yes. Yes. Is there a limit to what you would try?

Bryan Johnson

No.

David Friedberg

Interesting. Where do you think that comes from?

Bryan Johnson

I find it to be the most exciting configuration of life: the ability to play on the frontier, novelty, expedition, and challenge.

David Friedberg

Did you always have it, or are you responding to childhood suppression of those things?

Bryan Johnson

It's probably an overcompensation of a trauma response, like most things are. As a child, I lived in a very structured religious environment where things were cemented: Here's the story, here's the plan, here's what you do and what you don't do. So, yeah, maybe I'm now flipped in the opposite direction.

That's probably true. I really don't trust my internal generation of reality. I know I'm always making things up. I've got 188 cognitive biases, like all humans do. So I'm generally suspicious of all things, all the time, and I don't take myself very seriously.

I find the frontier play space to be—right now, what you're doing in building companies, you just open up a toolkit and say, "What can I build, and how do I modify it?" So I agree with you. I do have a strong proclivity toward open-ended play.

David Friedberg

Do you find that you've been challenged in maintaining what I would call external responsibility as you explore and enhance yourself so much? Do you give up responsibility to others around you who may be dependent on you or in need of you?

Bryan Johnson

Yeah. I have 3 kids, and I do think about them a lot. Being a father is a really important thing to me, and it's an important part of my identity. That has not changed. I've never vacillated on that or changed my disposition toward it.

For those around me, I guess fortunately I have a social group that just says, "Go and play." There's really no one in my life who tries to claw me back. There's no Velcro. It's all encouraging. I feel very fortunate that everyone around me is willing to take the risks.

When I sat down for 5-MeO, my partner, Kate, had a ton of risk. What if it goes poorly? What if I change my perspective? What if something bad happens?

David Friedberg

One could make an argument that taking that degree of risk, where something could have gone wrong, means the people around you are enabling rather than being supportive, right?

Bryan Johnson

That's right. That's right.

David Friedberg

Yeah, that's a consequence, but let's shift topics to other modalities for longevity. What else is on the horizon? You've had this profound set of experiences with psychedelics, and you've documented, in a very extraordinary and exquisite fashion, all of the other things that you've been doing with interventions. Are there other things on the horizon that you're either excited about or considering for yourself?

Bryan Johnson

Two of the ones that we've spoken about are cell therapy and gene therapy.

David Friedberg

Yeah. Yeah.

Bryan Johnson

They're all in the pipeline, so they're not ready yet. We've knocked out all the stuff you can do today. We've gone through it all and done it all. The next-generation therapies are just not there yet.

We're looking at mitochondrial rejuvenation. I think that's incredible. I think mitochondrial augmentation therapy is incredible. I saw a paper where, in order to get the mitochondria into the cell, they coated the mitochondria in effectively a red blood cell membrane, which made it more transportable into cells and less attacked by the immune system.

David Friedberg

Which is incredible. I'm a big, big, big believer in this course of therapy. I think it's going to be a whole therapeutic modality that no one has even recognized.

Bryan Johnson

We have our first mitochondrial therapy lined up.

David Friedberg

So how are you going to do it? You're 99.9%. You need someone who's 48.7% to try the mitochondrial therapy, particularly—I think they tried it in Parkinson's patients and Alzheimer's patients. That's where you can really see profound shifts in certain metrics. For you, it's 99.9% to what?

Bryan Johnson

Yeah, I had the mitochondria of a 48-year-old. What if I could—

David Friedberg

Yes. You could go to your sibling's child because the mitochondria is passed maternally, because it's in the egg cell. So it's the mother's mitochondria.

Bryan Johnson

Right. If you have a sister who has a kid, they're going to have very young mitochondria. You can take a little blood sample, then grow their mitochondria extensively and use that as a biological match to you.

I have a biological son. So now I'm just going to go to the extended family and be like, "Guys, it's a family project."

David Friedberg

Yeah, family project.

Bryan Johnson

Yeah, exactly. That one's super interesting. I have one that we're doing.

David Friedberg

Sorry, are you going to do your own mitochondrial transplantation? Are you going to build a bioreactor, or are you working with one of the third parties?

Bryan Johnson

Yeah, a third-party company. I'll do a blood draw in the next week or 2. They'll spin it up, and then we'll do it. Yeah, I'll do it.

David Friedberg

So you're going to get your mitochondria, which have some—the problem with mitochondria, as you know, is mitochondrial DNA degradation over time, right? It accelerates for certain people. That way, if you go back to a young person, you have young mitochondria. But then you're going to multiply yours out, and probably select a little bit for healthier ones, right? Okay. Then put it back in.

It's very exploratory. We don't know. We're one of the first. They're in phase 2 now.

Bryan Johnson

Do you sprint?

David Friedberg

Yeah, I do. You could probably score it if you did intramuscular mitochondrial therapy. You could sprint and see your score.

Bryan Johnson

That's a great idea. Yeah, thank you.

David Friedberg

That would be a great way to measure it rather than just from a basic biomarker perspective. It would be really interesting. Sprinting is one of the most underappreciated longevity therapies.

Yeah, I don't do it. Oh man. I've got the age of a 74-year-old, roughly. [Laughter.] I am 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? Like the one we were looking at involving FOXO3 expression?

Bryan Johnson

Yeah, exactly. The mesenchymal stem cells were packaged with the FOXO3 delivery. That showed that over 50% of tissues got that rejuvenation.

David Friedberg

It's unbelievable.

Bryan Johnson

Unbelievable. It's the best demonstration in the entire world for tissue regeneration. As a particular application set, tissue regeneration using that sort of system seems like a no-brainer.

David Friedberg

It's safe, right?

Bryan Johnson

Yeah, so I reached out to that Chinese professor. I'm really interested in seeing it replicated. I would love to—

David Friedberg

You reached out to the Chinese professor?

Bryan Johnson

Yeah. That's awesome.

David Friedberg

Yeah. We sent that paper. That's awesome.

Bryan Johnson

I'd love to do that. I'd love to actually build it ourselves. But that's like a 2-year project.

David Friedberg

Hey, I can help. Make it faster.

Bryan Johnson

That's true. Actually, that's true. AI as a project manager for these sorts of programs—that's true. We spoke about this 6 months ago.

David Friedberg

They're so different now, 6 months later, in terms of standing it up.

Bryan Johnson

That one's cool. I think that's a good option. Then also, I'm doing Bryan Johnson organoids. We took my iPSCs. We now have them—

David Friedberg

Induced pluripotent stem cells. So, you took your cells and turned them into stem cells.

Bryan Johnson

Yep. Now we're doing this in-dish. We have a Bryan Johnson heart, liver, and lungs. Now we're going to try molecules on me and in a dish.

David Friedberg

Let me just walk the audience through this. You take cells from your skin or from blood, and then you put these Yamanaka factor proteins on those cells. That causes those cells to become stem cells, which means they can then turn into any other cell. Then you put other proteins on them to turn them into a heart cell, an eye cell, or what have you. Now you've got a store of these tissue-specific Bryan Johnson cells.

Bryan Johnson

Yes, that you then use for—like, you can say, “Okay, what if you give Bryan Johnson a drug? What happens? Is it good? Is it bad? What are the side effects? What are the complications?”

David Friedberg

In a dish, you put the drug in there and see what happens.

Bryan Johnson

Yeah. Okay.

David Friedberg

Just like you can simulate all these experiments. Now you get the advantage of time and acceleration: what to take, why, what dose, and what combinatorial things to consider. That's awesome.

Bryan Johnson

We have the organoids stood up. We haven't done our first test yet. That's interesting, because now I have to do this old-school methodology: put it in my body and wait to see what happens. Is it good? Is it bad? How does it affect everything else?

David Friedberg

Yeah, totally. That's a good one. But we'll see. It's cool in concept. TBD if it actually works, so we'll see. Have you tracked any of the alternative Yamanaka-factor discovery work that's going on? Do you think there's anything worth testing at this stage?

Bryan Johnson

Yeah, I'm an investor in NewLimit. I've talked to them about where they're at. Blake and Bryan's company has made remarkable progress. They've figured out how to computationally solve the discovery process, and they're much faster than they initially thought. That's very encouraging.

David Friedberg

The big challenge with the Yamanaka factors is always dosing. If you overdose a cell—a single cell—that cell can become a cancer cell and take off as a tumor.

Bryan Johnson

Yeah. The sensitivity you need to have to get the right amount of the factors, which are proteins, into the cell needs to be perfectly tuned. I have a theory that this will end up being solved by cellular switches that put machinery into the cells that can turn protein synthesis on or off at the right dosing, based on the measurement of gene expression in the cell. That's my theory on where this will end up.

David Friedberg

That makes a lot of sense. Any other control mechanism will be inadequate.

Bryan Johnson

That's right.

David Friedberg

The feedback loop—all you need is 1 error, and you're in trouble. It is the most profound technology, I think, that humanity is dealing with today besides AI. We're not quite there with fusion, which I would argue is probably a distant 3rd, but it is very powerful if possible.

Bryan Johnson

Again, in the future, I think we'll look back and see GLP-1s as the first big drop. I'm like, “What? I can just inject myself and it solves hunger?” The second will probably be something like NewLimit or one of these plasma-based FOXO3 therapies, where it will show real-life, dramatic changes. Then humanity will shift, as longevity goes from being a vision of science fiction and a rich-person pursuit to something that is truly—

David Friedberg

Yeah, I mean, go back to the conversation about the temptation toward socialism. If you can feel robust in your ability to pursue life and be healthy, vibrant, and in control, I think these things could have dramatic changes in society, not just in health, but—

Bryan Johnson

Well, any form of abundance—whether it's abundance in food, energy, housing, mobility, or life—the more abundant people get, the happier they are. 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.

David Friedberg

Exactly. The happier we will all be with each other. But I think, honestly, a lot of the—

Bryan Johnson

External conflict only comes from internal unhappiness.

David Friedberg

100%. So, if you look at the general malaise of American society, no wonder things are shitty, right? 84% of people have metabolic disorders. Over 40% of people are obese. We're just in really poor health. Nobody's sleeping. Everyone's on their phone. There are mental health issues. No wonder you have a proclivity toward these kinds of outcomes. If you could get the health in check, it changes the psychological disposition of you, your community, and your country. You have much more of a can-do attitude: “I can take on the world, and I can do hard things.” But when you're not feeling well, everything is just so much harder.

Yeah, 100%. In light of all these new therapeutic modalities and opportunities that seem to be biologically proven and have these profound effects, why continue to tinker with psychedelics? Are they as profound, or are they a complement? How do you think about fitting this entire portfolio of things you're looking at together?

Bryan Johnson

Yeah. I guess the question is—I forget—on the FOXO3 study, I don't know if they saw brain rejuvenation.

David Friedberg

I did not see that, and I don't remember. It is a very complicated organ. It's insane. You can grow muscle tissue back, and you can grow skin tissue back, and it's kind of like, “Okay, I grew a little.” If you grow the neurons back, maybe in the wrong way, we don't know, because it's never been done before.

Bryan Johnson

Yeah. So, understanding the consequence of neuroregeneration is important. I wonder what role it might play. Maybe psilocybin and 5-MeO won't be meaningful for basic functions of the body, but maybe they're the outperformer in the youthfulness of your disposition toward reality.

One thing I'm apprehensive about is that I'm 48. As you start climbing into your 50s and 60s, you really narrow. Your ambition goes from “I can do anything” to narrowing down further and further. I worry about losing a youthful disposition, a can-do attitude, and the belief that anything is possible. Maybe that's the role of psychedelics: you get a wash of the snapback of “I can, and I can bounce.” That's definitely been the case for me.

I think they probably play a really important role. I felt like it was 30 or 40 years of psychological rejuvenation. It transformed me back to a childlike state. That's insane. I don't get that from the sauna, eating well, or sleeping well. I'm still—

David Friedberg

Right. They're just unique. Yeah, amazing. Well, listen, I'm going to go drink alcohol, eat carbs, and stay out late. I don't know—what are you going to do?

Bryan Johnson

I'm going to go to bed on time and do my wind-down routine.

David Friedberg

Yeah, you do you. But you do you as well. Enjoy it. I appreciate it. This has been great. Bryan Johnson, thank you.

Bryan Johnson

Yeah, that was awesome. That was great.