I am curious whether curcumin, caffeine or peptides can actually cross the skin barrier. My understanding of the physiology would be that they can not. But maybe they can enter into the hair follicles themselves?

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They are supposed to make you feel good about yourself when you wash your hair with snake oil shampoo.

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@Virilius Making me feel good about my recent purchase over here! lol

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Thanks for this info. I will certainly look into it when I have the time

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@relaxedmeatball
I know you’ve said this about exosomes, but now I’m hearing your thoughts on other molecules.

For clarity, are you saying that in your opinion all the skin care products with peptides most likely don’t do anything? Do you feel the same about vit c, ceramides, etc? Or possibly, you might think they help improve the surface of facial skin, but perhaps it’s not going deep enough to stimulate hair growth?

I’ve seen reports of great clinical outcomes of those things when delivered via mesotherapy OR via DEP.

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Hey Beth, well I think the same rules apply. Your skin is a barrier, evolved to keep most things out, and to keep your parts inside. So it’s really very impermeable to most things. The top layers are made of flattened, dead cell skeletons, with a super tough and insoluble protein (keratin), which is surrounded by a bunch of fats. People describe this as “brick and mortar” if that helps to visualise it. Below that, you have live cells which are linked to each other by proteins that kinda suture them together (tight junctions). Below that you have a basement membrane, which is a layer of protein. In order to reach the dermis (where collagen, elastin etc is), you need to get through all of those layers.

Things which can pass well through the skin tend to be small and fat soluble - so things like ceramides, steroid-based molecules (corticosteroids, oestrogen, testosterone etc). Something like a peptide is relatively large, water soluble, so the penetration through the skin isn’t going to be great. Ceramides are a type of lipid, so they will integrate into the skin (mostly the epidermis) and improve barrier function. Vitamin C has very poor penetration, which I tested for myself in the lab using mouse skin. Some formulations might have a better chance because they mix it with lipids etc.

That said, all of that applies to a sort of model “normal” skin. In reality, skin on your forearm, lip, eyelid, palm etc are quite different and will allow things through at different rates. You also have appendages, like sweat glands, hair follicles etc which some molecules can enter. So I’m not making any sort of blanket statement like “a peptide can never cross the skin”, or “this will never work”, but I am a little sceptical unless there’s some supporting evidence. Also, consider that from a regulatory point of view, if something cross the epidermis and enters the dermis, it has access to the blood stream - that makes it a transdermal drug, not a cosmetic. (Think fentanyl patch, hormone replacement gels etc - they are all transdermal drugs).

Also, I am making an assumption that something needs to cross the barrier in order to “work”. But if we take something like hyaluronic acid, that’s a pretty big molecule which won’t diffuse easily across the epidermis. However, it does get stuck in the epidermal layers and it soaks up water, producing a hydrating and plumping effect. So cosmetically it does work. So maybe exosomes have some similar effects.

Lastly, something like microneedling or nanoneedles totally changes the game because you’re punching holes right through that epidermal barrier.

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Thank you for this masterclass on skin. It seems some things might improve the look of skin because it’s only attacking the surface (and fine with me!!) , but it’s much harder to go deep and do things like affect collagen or even hair growth etc.

I’m saving it to refer to !

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https://x.com/bryan_johnson/status/1955333164622315878#m


Bryan is actually not wrong, and systemic markers is a good idea.

Absence of night time erections can also be a marker of a disease state like damage in the small veins by excess blood glucose, high BP, atheroclerosis (apoB), etc, where symptoms can be improved but not the disease reversed yet. That might be a mostly symptomatic improvement.

Every single thing can be hacked or deviate in a way that improves the score without the benefit. So the improvement should strive to have the benefit.

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We’re all going to make it.

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So they’re using BJ as bait so people start reading, 90% of the article is just Peter Attia.

Personally I hope to have a 35-65% split, but dunno.

I find it interesting Peter has warmed up to the speed of aging clocks. Depending on how much sun in Peter’s studio maybe one day BJ will be on his podcast. :wink:

The Billionaire Who Wants to Live Forever | Bryan Johnson

We’re all going to make it.

Make what? Unless BJ become’s Maxwell’s demon he hasn’t changed anything about existence—people will still die eventually. Whether you go in 100 years or in 100 million you still have to come to grips with non-existence, so Jesus will always be on the market.

And besides, even if we do cure and reverse aging, accidents happen (whether it’s little like your heart going asystolic or big like your solar system going supernova) and probably nobody is going to make it to 100 million.

But as long as you keep drinking the kool aid he’ll be able to sell $59 shampoo (lol) and $119 scalp serum (lol) with peptides that he doesn’t even know which is which.

Like for example, the “sh-oligopeptide 4” that he thinks is equivalent to VEGF, but is actually just recombinant thymosin β4. Not that it would matter, since he has zero data (despite claiming to base everything upon data) that these are topically absorbed.

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Humble 178 dollar shampoo salesman.

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Peptide shampoo salesman ingredients.

Has these things been tested in humans? What do they do? Do people just take stuff?

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https://x.com/bryan_johnson/status/1958233605010076006#m

I feel like I should just do my own thing, I disagree with all of the longevity influencers in different ways, it’s kind of annoying me when I feel like I know a better approach. I’m not going to be a influencer for this of course.

The correction impulse…

And Bryan seems to be mostly “art project about AI” so he feels alienating in some ways.

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A new BJ video:

AI Summary:

This video features Bryan Johnson discussing his journey, the “Don’t Die” philosophy, and the future of human longevity.

Key Points from the Video

1. Bryan Johnson’s Public Persona and Openness

  • Johnson reflects on his transition from being sensitive about public scrutiny to embracing openness, especially regarding personal topics like his use of an erection monitoring device. He describes how initial apprehension gave way to acceptance as he realized the public’s interest and the power of transparency. ​⁠
  • He discusses how talking about sleep and its impact on sexual health grabs people’s attention, making it an effective entry point for broader health conversations. ​⁠

2. Early Health Experiments

  • Johnson recounts his early, unconventional health experiments, such as snorting platelet-rich plasma (PRP) for brain health and trying 5-MeO-DMT from the Sonoran toad for consciousness expansion. He explains that these were part of his quest to map different states of consciousness and push the boundaries of self-experimentation. ​⁠
  • He notes that these practices wouldn’t pass his current “Blueprint” standards for evidence and safety, highlighting his evolution toward more rigorous, science-based protocols. ​⁠

3. Personal Transformation and Leaving Mormonism

  • Johnson shares his background as a devout member of the Church of Latter-day Saints, marrying young, starting a family, and building a billion-dollar business. He describes a period of mental health struggles, divorce, and leaving the church, which led to a process of self-reinvention and experimentation. ​⁠
  • He discusses the challenges of transitioning from a tightly knit religious community to the broader world, emphasizing the need to rebuild mental models and skill sets. ​⁠

4. The Blueprint Longevity Business and Burnout

  • Johnson talks about his decision to step away from running Blueprint full-time, citing burnout and the need to focus on new projects. He describes Blueprint as both a personal health protocol and a business, and explains the challenges of scaling it while maintaining scientific rigor. ​⁠
  • He emphasizes that his motivation was never about money, but about solving his own health problems and helping others. ​⁠

5. The “Don’t Die” Philosophy and Ideology

  • Johnson and interviewer Ashlee Vance explore the intellectual underpinnings of the “Don’t Die” philosophy, which Johnson positions as a new ideology for a world facing rapid technological change and the possibility of radically extended lifespans. ​⁠
  • Johnson argues that traditional belief systems are inadequate for a future where death may not be inevitable, and that “Don’t Die” is about embracing humility and preparing for unprecedented change. ​⁠
  • He describes efforts to build community around “Don’t Die,” including events, rituals, and thought experiments designed to help people adapt to a changing world. ​⁠

6. Fame, Hate, and Social Dynamics

  • Johnson shares insights on handling fame and hate, suggesting that negativity can be transformed into a source of energy and power. He discusses the isolating effects of wealth and fame, and the importance of finding trusted communities. ​⁠
  • He describes participation in private influencer groups and the behind-the-scenes nature of business and social relationships in Silicon Valley. ​⁠

7. AI, Mortality, and the Future

  • Johnson’s views on artificial intelligence have evolved from seeing it as an existential threat to recognizing its inevitability and the need for careful navigation. He believes AI will cause major societal disruptions, requiring new frameworks for meaning and security. ​⁠
  • He positions “Don’t Die” as a practical, humble response to the uncertainty of the future, advocating for clear-mindedness and adaptability. ​⁠

8. Darkness Retreat and Modern Life

  • The video ends with a discussion about a planned darkness retreat in Poland, which Johnson sees as an opportunity for self-experimentation and mental reset. The retreat is described as a response to the overstimulation and device-dependence of modern life. ​⁠

This video offers a deep dive into Bryan Johnson’s personal journey, his evolving philosophies on health, technology, and existence, and his vision for a new ideology to help humanity

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I just don’t get it, how can that be related to “being hot” as he mentioned in the interview, and that 1 billion people will follow adjacent to “Don’t Die” which includes “being hot”?

Besides he should probably do fund a study on which message is the best, just like the lab grown meat industry found “cultivated” or “cultured” meat was most preferable over e.g lab grown.

In September 2019, GFI announced new research which found that the term cultivated meat is sufficiently descriptive and differentiating, possesses a high degree of neutrality, and ranks highly for consumer appeal.[28][48] A September 2021 poll indicated that the majority of industry CEOs have a preference for cultivated meat, with 75 percent of 44 companies preferring it.[49]

Bryan Johnson seems to be front-running this trend:

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I’m skeptical because Bryan only posted ChatGPT things a few times, just like everyone has tested – and he does admit he has an eccentric personality.

You’re underestimating the reach and popularity of the Bryan brand. I mean for us it’s like everyday stuff but he is a celebrity.

Besides philosophers have talked about similar directionality or action as Bryan is taking, meaning being ambitious and thinking in terms of billions of humans, it could just be seen for example as an extension of one’s own consciousness. If I remember correctly it could be phenomenology specifically Heidegger’s Dasein as an example:

Dasein[6] for Heidegger is a mode of being involved with and caring for the immediate world in which one lives, while always remaining aware of the contingent element of that involvement, of the priority of the world to the self, and of the evolving nature of the self itself.[4]

So naturally you could become ambitious and think in grand themes without being psychotic. Add on top of that actually being a celebrity and having reach in this area, it doesn’t seem that unhealthy to me. It can be some form of existential phenomenology actually, I think that’s more correct what I mean rather than dasein per se but which is a part of it, see this lecture, but there’s a better lecture somewhere that hits the point home exactly:

But personally once I started to think about it there could be so much responsibility I’d rather just do smaller things, lol.

ChatGPT as God is a mental illness. However, if we were to live in a simulation, as some suppose, I would assume God to be akin to an all powerful hyper advanced AI.

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