Hi there, it’s Mehdi Yacoubi, co-founder at Vital, and this is The Long Game Newsletter. To receive it in your inbox each week, subscribe here:

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📣 Announcement: I’m very excited to announce Vital’s pre-seed round led by Samuel Gil and with great angel investors, including Balaji Srinivasan, Qiao Wang, Kenneth Schlenker, Robert Miller, Gonz Sanchez, Adam Gries, Robert Lufkin, MD, Ilan Benhaim, and many more!

📣 We are hiring (all the openings):

If you know the right people for this journey, please let me know. We’re offering $1,000 in Bitcoin if you refer a candidate we end up hiring.

In this episode, we explore:

Alcohol consumption and aging
Friendships
Understanding the assumption stack of your mentors
What You Do is Who You Are
Printing organs

Let’s dive in!

🥑 Health

🍺 Alcohol Consumption and Aging

Here’s an unfortunate study for those who enjoy a cold beer or a glass of wine. It shows that alcohol consumption accelerates aging.

Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with incidence of diseases and death, less is known about how it is related to lifestyle behaviors.
Among 2,316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking.
Whole blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess four epigenetic clocks and their corresponding metrics of epigenetic age acceleration.
Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel.
In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel.
Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

On this topic, I’ve been following the growth of the non-alcoholic or low-alcoholic alternatives as I believe it will be the future. Fitt Insider had a great issue about it.

In 2019, alcoholic beverage sales in the US surpassed $250B.
But there’s a catch: 43% of drinking-age Americans don’t consume alcohol. And 40% say they’re drinking less than they did five years ago.
Driving this trend, 66% of US millennials said they’re making efforts to reduce their alcohol consumption, citing motivating factors like well-being and weight loss. A sign of what’s to come, Gen Z is consuming less alcohol than previous generations.
Globally, the World Health Organization expects the proportion of drinkers to fall by 1.4 percentage points to 40.3% between 2020 to 2025.

🌱 Wellness

🙏 On Friendship

A beautiful read on friendship, good friendships, bad friendships, and more.

These are the friendships that fill our souls, and bolster and shape our identities and life paths. They have also been squeezed into social science labs enough times for us to know that they keep us mentally and physically healthy: good friends improve immunity, spark creativity, drop our blood pressure, ward off dementia among the elderly, and even decrease our chances of dying at any given time. If you feel you can’t live without your friends, you’re not being melodramatic.
But even our easiest and richest friendships can be laced with tensions and conflicts, as are most human relationships. They can lose a bit of their magic and fail to regain it, or even fade out altogether for tragic reasons, or no reason at all. Then there are the not-so-easy friendships; increasingly difficult friendships; and bad, gut-wrenching, toxic friendships. The pleasures and benefits of good friends are abundant, but they come with a price. Friendship, looked at through a clear and wide lens, is far messier and more lopsided than it is often portrayed.

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🧠 Better Thinking

🗯 Understanding the Assumption Stack of your Mentors

I often come back to the idea that giving advice doesn’t really work in many cases. It’s a mix of a survivorship bias and giving advice to ourselves that we make universal when it should not.

While listening to Bryan Johnson last week, I really liked his perspective on advice. He explains:

Listen to advice and see it for what it is: a mirror of that person, and then map and know that your future is going to be in a zeroth-principle land. What you’re hearing today is a representation of what may have been the right principle to build upon previously, but they’re likely depreciating very fast. I’m a strong proponent that people ask for advice but they don’t take advice.
So how do you take advice? It’s in the careful examination of the advice. The person makes a statement about a given thing that we should follow. The value is not in doing that. The value is in understanding the assumption stack they built around that body of knowledge.

We tend to love “recipes,” frameworks, and playbooks, but you can’t follow something blindly and expect it to work.

⚡️ Startup Stuff

💼 What You Do is Who You Are

I read What You Do is Who You Are by Ben Horowitz over the last couple of weeks, and it’s a great read on company culture. At the time we’re starting to shape Vital’s culture, I enjoyed having the perspective of Ben Horowitz on this matter.

Here are a few notes on the book:

Every business owner and CEO knows the importance of workplace culture, even if they might struggle to define it. Creating the perfect environment for people to work in and making sure the whole company approaches work with the right attitude can be just as important—and just as hard—as developing the perfect product.
Culture isn’t the same as values—values are more like aspirations, while culture means something in practice. Culture varies a lot from one company to the next.
The example of Toussaint Louverture: the man who abolished slavery in Haiti. Through big decisions that clearly communicated values and culture, he was able to shape a special culture in his army. He understood that his decisions had to demonstrate his cultural priorities.
One idea I liked: using shocking rules. Amazon’s frugality, or starting every meeting 5 minutes in advance, are examples of this.
On acting right: when it comes to doing difficult things like delivering hard truths, why you do good isn’t as important as the simple fact that you do. Regardless of your motivations, it’s our actions that define us.
I loved the prison story of Shaka Senghor: while being the boss of a prison gang, he shaped a better culture through constant engagement.
The story of Uber is very interesting: the insane value put on competition led to very bad internal behavior.
On choosing the right virtues: it’s difficult to generalize because they have to come from you and your business. But there are some broad points you should consider. First, your new hires should embody these virtues. Then, the virtues should be actionable. Finally, your virtues should distinguish your company from the competition.
Culture is not static. It needs to be redefined when necessary. A wartime CEO has to place victory ahead of protocol on occasion and needs to act fast. A peacetime CEO focuses more on good protocol and longer-term success.
Trust and loyalty should be universally maintained.

Finally, always remember that staying calm is a superpower : )

📚 What I Read

🚂 Why do we need to know about progress if we are concerned about the world’s large problems?

Another one from the great team at Our World in Data on why it’s important to focus on our biggest problems.

Progress means solving problems. This makes it necessary that anyone who wants to contribute to solutions needs to study both:
If you care about problems you need to study progress. The progress we achieved gives us the opportunity to learn how we solved problems in the past and – most fundamentally – to know that progress is possible.
If you want to make progress you need to study problems. Every problem we identify is an opportunity to make progress. To make the world a better place the first step is to understand the problems we are facing today.

⭐ Silicon Valley’s ‘Mission Protocol’ Revolution Is Beginning to Attain Critical Mass

On being a mission-focused company:

These entrepreneurs have always understood what so many progressives seem incapable of processing: building products that other people will buy requires not only hard work, talent, and a spirit of innovation, but also monomaniacal focus.

🛣 How to Do Long Term

Playing the long game is easier said than done—great piece by Morgan Housel detailing a few essential points.

Your belief in the long run isn’t enough. Your investors, coworkers, spouses, and friends have to sign up for the ride.

🎙 Podcast Episodes of the Week

Too many great episodes were released recently. It’s hard to catch up!

🍭 Brain Food

🖨 The Science Fiction World of 3D Printed Organs

What if we could print new organs for people who need them? This science-fiction concept is not so far from becoming a reality. Bioprinting could end up saving millions of people’s lives each year.

3D printing holds the promise of changing the healthcare industry for the better by offering products such as smarter drugs and hyper-customized prosthetics. However, like something out of the 1990 film Dark Man, in the near future, it might become commonplace for doctors to treat patients with printed organs. In fact, this is already happening. Researchers from various leading universities have 3D-printed functioning human organs. This could help to address the shortages of donor organs around the world, and especially in the United States.

This is an incredible perspective because the demand for organs is very high, and an organ transplant is extremely costly.

For example, according to the National Foundation for Transplants, a standard kidney transplant, on average, costs upwards of $300,000, whereas a 3D bioprinter, the printer used to create 3D printed organs, can cost as little as $10,000 and costs are expected to drop further as the technology evolves over the coming years.

The technology is far from being perfect today, but it will improve with time.

To print an organ, scientists need to deposit cells specific to the organ they are building. For example, to create a liver, they would start with hepatocytes — the primary liver cells — as well as other supporting cells. As the cells are printed and accumulate on the platform, they are embedded in a microgel support matrix (or scaffold) and assume the shape of the organ. Scientists could also start with a bioink (a suspension of living cells) consisting of stem cells, which can differentiate into the desired target cells.

🎥 What I’m Watching

🤖 The Machine

What if people could renounce their life permanently for a virtual life inside a machine? Pursuit of Wonder is very clairvoyant when it comes to understanding the challenges we might face in the future.

📜 The Story of Atrium

Our failures teach us more than our successes. This is a very interesting video where Justin Kan shares his introspection into why Atrium failed.

🔧 The Tool of the Week

👥 Clay—Be More Thoughtful with the People in Your Network

I’ve been looking for the perfect personal & professional CRM for a while. I haven’t found it yet. There are many great tools, but nothing works well with my existing setup. I remember this piece about how Peter Boyce organizes his social connections on Airtable; he does it masterfully. I’m much less organized than this!

This week I found this cool tool: Clay. I haven’t tried it yet, but it looks beautiful, a little bit like Superhuman for CRM.

🪐 Quote I'm Pondering

Infinite players cannot say when their game began, nor do they care. They do not care for the reason that their game is not bounded by time. Indeed, the only purpose of the game is to prevent it from coming to an end, to keep everyone in play.

— James Carse

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👋 EndNote

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Until next week,

Mehdi Yacoubi

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The Long Game by Mehdi Yacoubi

The Long Game 57: Alcohol Consumption …