The Long Game 45: Rapamycin Human Trial, Finding a Hobby, Being Out There, The Righteous Mind

🍷 In Vino no Veritas, The State of Venture Capital, Privacy and Note-Taking Apps, The Curse of Creativity, and Much More!

Mehdi Yacoubi

Mar 21

Hi there, it’s Mehdi Yacoubi, co-founder at lifetizr, and this is The Long Game Newsletter.

Greetings from Paris 🇫🇷

In this episode, we explore:

A Rapamycin trial for longevity
Finding a hobby you won’t obsess about
Being out there
The state of venture capital
The Righteous Mind
In vino no veritas

Let’s dive in!

🥑 Health

💊 Rapamycin Human Trial for Longevity

One of the biggest problems of the anti-aging field right now is the lack of human trials to see whether some compounds actually slow down aging in humans or not. I was delighted to see that my friend Anar Isman, co-founder at AgelessRX, a digital pharmacy for anti-aging drugs, is working on human trials for Rapamycin and Metformin—two of the most promising anti-aging drugs.

Here’s an abstract of Nathan Cheng’s great newsletter:

AgelessRX, a DTC online pharmacy for anti-aging compounds, is crowdfunding a 200-person Phase 4 clinical trial of rapamycin. Rapamycin is one of the most well-studied anti-aging drugs (for mice it extends lifespan ~ +15%). But because it is off-patent there is no profit incentive for pharma companies to conduct a clinical trial.
AgelessRX is looking to raise a total of $800k from two sources:
Trial participants ($1000 / each) who will receive $3000 worth of biomarker testing during the trial (DNA methylation clock, blood tests, glycation age test, DEXA scans, gut microbiome sequencing, etc)
Donations from individuals and organizations.
It appears AgelessRX is only $200k away from reaching its goal for donations. If you are interested in either enrolling for the trial or donating please check out the PEARL trial webpage.

I keep talking about longevity because it’s a scientific field that’s just getting started, and it depends on us whether it will really take off in the 2020s or only later.

Qiao Wang @QwQiao

I’m a big advocate of longevity research not because I fear death, but because I love life. My family. My friends. I’d like to live long enough to see how the future of humanity looks like. To see us conquer climate, land on Mars, and mine the last block reward of Bitcoin.

We talked about longevity escape velocity in The Long Game 22, and it’s worth remembering this concept to grasp the urgency of acting and investing in longevity:

Longevity escape velocity is a hypothetical situation in which life expectancy is extended longer than the time that is passing. For example, in a given year in which longevity escape velocity would be maintained, technological advances would increase life expectancy more than the year that just went by.

Whether it happens in 2036, 2056, or 2096 depends on us. If it happens in 2096, we’ll be among the unluckiest generations in history. Here’s the latest prediction by Aubrey de Grey:

Aubrey de Grey @aubreydegrey

I now think there is a 50% chance that we will reach longevity escape velocity by 2036. After that point (the "Methuselarity"), those who regularly receive the latest rejuvenation therapies will never suffer from age-related ill-health at any age.

🌱 Wellness

🎣 Finding a Hobby you Won’t Obsess About

A while ago, I read a piece explaining that if you’re really intense in your work life, you should find a hobby you won’t obsess about. I have kept thinking about it ever since. Increasingly, I understand the importance of this as I’ve been through the intense work-life of building a company for almost a year now.

I like to put intensity in my work and some other activities like the gym, martial arts, and more. Still, there is something particular about doing an activity just for fun and not necessarily trying to get better at it.

Tell me if this sounds familiar: You pick up a new hobby, eager to get some downtime. Painting maybe, or gardening, or shadowboxing. At first, you enjoy learning the ropes. You buy basic equipment. You spend a few hours here, a few hours there, but, as an amateur, you’re not worried. Your new hobby helps you relax. Then, your winner’s instincts kick in.
Suddenly, you can’t stop. You paint for hours. You watch every Youtube video on growing tomatoes you can find. You can’t wait to knock your teacher off the leaderboard. What happened?

Obsession is a strength but can easily turn into your biggest liability. That’s why finding a hobby you won’t obsess about is essential. I haven’t found it yet, but some of the contenders are spearfishing and hunting (I’m a JRE fanboy, and I admit it :)) Right now, these hobby are going to be complicated to practice in Paris, but that’ll be resolved soon (stay stunned; I’m preparing something cool on this front!)

Watching a few episodes of Meat Eater definitely convinced me to get more of this wildlife lifestyle!

Nat Eliason @nateliason

I think my new favorite intellectual demographic is crypto prepper bro, people who are into: - crypto - privacy - hunting - cooking - homesteading - the creator economy what else fits in that bucket?

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🧠 Better Thinking

✍️ Being Out There

"The best way to get the right answer on the internet is not to ask a question; it's to post the wrong answer."

— Cunningham's Law

This law encapsulates perfectly why being out there and writing on the internet is an excellent way to develop your thinking and find better answers to the questions you’re working on.

I wrote in The Long Game 11:

Reading, watching, or listening content can help you think better and learn new things, but it will only get you that far.
Writing is when understanding and consolidation of knowledge happens.
The main reason I started this newsletter was to balance out the input of information with the output. It forces me to gather my ideas, and I have to admit it's much harder than I thought.
The moment you go from passively consuming information to actively producing it changes everything. You quickly realize that you didn't understand the concepts as well as you thought you did. Then, you're not merely reproducing the information, but you might end up contributing with something yours, your thoughts, your ideas, reflections!

34 episodes later, I can still confirm this. On top of pushing you to create, writing online gives you feedback, and this feedback helps you course-correct efficiently.

I try always to remember that:

It’s not “write about it if you know about it.”
It’s “write about it so you will know about it.”

⚡️ Startup Stuff

💰 State of Venture Capital

In the last episode of the All in Podcast, Chamath shared a very interesting deck about the state of Venture Capital. As a founder, I’m not a VC, but I think it’s important to be aware of the dynamics in the venture capital space. It’s changing rapidly, and here are some of the key points to be aware of:

On top of institutional investors, we’re now seeing the rise of “solo capitalists” and the atomization of established firms.

Erik Torenberg @eriktorenberg

Founders don't want to raise money from institutions as much anymore. They want to raise money from individuals.

The most important idea here is that founders will increasingly seek seed funding from individuals and syndicates. Then, they will look for non-dilutive funding for the A, B, C, E rounds through a solution like Pipe (here’s a breakdown of Pipe by Alex Danco), and finally go public through a SPAC.

Robin Wauters @ Tech.eu @robinwauters

I saw a guy today from the investment industry. He had no SPAC, no Clubhouse app. He just sat there drinking his coffee. Like a psychopath.

📚 What I Read

⚖️ The Righteous Mind: Why Good People are Divided by Politic and Religion, by Jonathan Haidt

This week I’m reading The Righteous Mind by Jonathan Haidt, and I absolutely love it. He explains so well why we have such a tough time discussing ideas with other people.

Here are some of my notes on what I found worth remembering (first half of the book only as I haven’t finished it yet):

The obsession with self-righteousness is a feature of the human mind
Intuition comes first, strategic reasoning next
Morality differs in different places of the world
We’re born to be righteous, but we have to learn what, exactly, people like us should be righteous about
Don’t think emotions vs. cognition, but intuition vs. reasoning
If you want to change people’s minds, you need to trigger new intuitions. Begin in a friendly way. Be open to the dialog (cf. How to Win Friends and Influence People)
Henry Ford said: “if there is any one secret to success, it lies in the ability to get the other person’s point of view and see things from their angle as well as your own.”
3 models of the mind—Plato: reason ought to be the master—Hume: the reason is the servant of the passions—Jefferson: reason and sentiment are independent co-rulers
Hume is right according to Haidt
Our moral thinking is much more like a politician searching for votes than a scientist searching for truth

People bind themselves into political teams that share moral narratives. Once they accept a particular narrative, they become blind to alternative moral worlds.

I highly recommend this book to anyone that wants to be a productive element of the civil discourse.

📖 Other good readings of the week

It’s time to Build a New World Fair—a call to action to build a new world fair.
Biotech for the biocurious—resources to get started in biology

🎙 Podcast Episode of the Week

A new batch of episodes of The Long Game Podcast will be released in a few weeks. In the meantime, here are some episodes I enjoyed from other shows:

Silvio Micali: Cryptocurrency, Blockchain, Algorand, Bitcoin & Ethereum—a great conversation about everything related to cryptography and how it will evolve in the future.
Jamie Metzl—On the origins of Covid and the future of genome editing. I find the perspectives of genome editing both incredible and scary. We really need to get the conversation started about this before it’s too late.

🍭 Brain Food

🍷 In Vino no Veritas

For all the wine enthusiasts out there, this research paper is for you! It will maybe make you rethink how much money you’re spending on pricy bottles. Here’s the abstract. It’s a thought-provoking one.

Past experimental laboratory and correlational data from observational research has shown that knowledge of the price of wine influences the consumer’s subjective experience. However, there is limited prior research that has explicitly manipulated price information in a realistic wine tasting setting.
A total of 140 participants tasted three different low-, mid- and high-priced wines with open, deceptive, or no price information and rated them for taste intensity and pleasantness. In our community sample, intensity of taste ratings for open, deceptive and blind price information reflected retail prices, thus more expensive wines were rated as more intense in taste. However, while pleasantness ratings did not differ for open and no price information, deceptive up-pricing of low-price wine significantly influenced ratings for pleasantness, whereas deceptive down-pricing of high-price wine had no effect on pleasantness ratings.
Thus, pricing information differentially influences the consumer’s subjective experience of wine, with no effects on intensity of taste ratings and no effects on pleasantness ratings with correct or no price information, but increased pleasantness of low-price wine when provided with a deceptive higher price. Thus, in wine may lay the truth, but its subjective experience may also lie in the price.

For more on this topic, I know the book Alchemy explains the details of how this works. I haven’t read it yet, but here’s a great commentary (in Spanish) about it by my friend Samuel Gil.

Samuel Gil @samuelgil

Es humor, pero hay mucha verdad

🎥 What I’m Watching

📛 The Curse of Creativity

In this story, we follow one of the 20th century's most prominent writers as she provides insights into her creatives process and the success of her work, only to eventually find out one of the most important factors was something she was unaware of.

🔧 The Tool of the Week

🔓 Standard Notes

I know that I talk too much about note-taking tools. Recently, I started to adopt a different vision about productivity. No tool is really going to make you more productive. The whole industry around productivity is kind of BS. You just need to focus on what matters, but this doesn’t sell.

Security and privacy, however, are far from being BS. I started to be much more mindful about online security, and I realized that everything I’ve been saving on Notion & Roam isn’t necessarily safe. Standard Notes on the opposite is a safer place for your important notes. It’s a free, open-source, and completely encrypted notes app.

🪐 Quote I'm Pondering

“The most difficult subjects can be explained to the most slow-witted man if he has not formed any idea of them already; but the simplest thing cannot be made clear to the most intelligent man if he is firmly persuaded that he knows already, without a shadow of doubt, what is laid before him.”

— Leo Tolstoy

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👋 EndNote

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Until next week,