The Long Game 50: Epigenetic Age Reversal, Don't Try, Mental Health at Startups, Languishing

👨‍🚀 The Expansion of the Universe, The Sovereign Lifter, Nuclear Energy, Poolside FM, and Much More!

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

Greetings from Montenegro 🇲🇪

If you missed the past episodes, you could catch up here.

In this episode, we explore:

  • Reversal of Epigenetic Age Using Lifestyle Interventions

  • Languishing and How to Feel Good

  • Don’t Try

  • Mental Health at Startups

  • The Expansion of the Universe

Let’s dive in!


🥑 Health

⌛ Reversal of Epigenetic Age Using Lifestyle Interventions

I read this study this week, and it’s worth sharing. Here’s the abstract:

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72.

The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention.

Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013).

The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009).

To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.

I strongly believe that this will be the future of health optimization. No need to be dogmatic about what health practices work/don’t work anymore. People will be able to try some lifestyle intervention and monitor the effects on their epigenetic age. This way, people will manage to age much slower, waiting for more anti-aging therapies to be developed.

Bringing bio-feedbacks to people to help them make the right health choices will be a game-changer.

Here’s the example of Michael Lustgarten showing how he manages his own optimization. The process is still relatively complicated, but we will make it much simpler in the future.

📈 Related to this, we talked about testosterone optimization last week. If you’re interested in optimizing your testosterone levels using nutrition, exercise, sleep, and supplements, fill in this form.


🌱 Wellness

🧩 Languishing and How to Feel Good

I found the concept of languishing explained by Adam Grant in this piece to be worth sharing. Having the right words to talk about how we feel is essential. Lately, words like “depression” and “anxiety” are used a lot, but people often use them outside of their clinical significance. Languishing is a good addition to the mental health vocabulary:

In psychology, we think about mental health on a spectrum from depression to flourishing. Flourishing is the peak of well-being: You have a strong sense of meaning, mastery and mattering to others. Depression is the valley of ill-being: You feel despondent, drained and worthless.

Languishing is the neglected middle child of mental health. It’s the void between depression and flourishing — the absence of well-being. You don’t have symptoms of mental illness, but you’re not the picture of mental health either. You’re not functioning at full capacity. Languishing dulls your motivation, disrupts your ability to focus, and triples the odds that you’ll cut back on work. It appears to be more common than major depression — and in some ways it may be a bigger risk factor for mental illness.

According to psychologists, the first step to feeling better is to name your emotions and your feelings. After that, a solution to languishing might be to seek moments of “flow.”

A concept called “flow” may be an antidote to languishing. Flow is that elusive state of absorption in a meaningful challenge or a momentary bond, where your sense of time, place and self melts away.

A lot of other things might help people to feel better and be generally happier. Justin Kan has a great guide detailing things you could try to feel better.


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🧠 Better Thinking

🚫 Don’t Try

After achieving fame, German-American poet, novelist, and short-story writer Charles Bukowski had one piece of advice for other writers seeking literary success:

Don’t Try

Bukowski was adamant that the writing should burst out without coercion or commercial ambition.

You don’t try. That’s very important: not to try, either for Cadillacs, creation or immortality. You wait, and if nothing happens, you wait some more.

I thought about this for the whole week. It’s very different from the usual advice we often hear: hustle, try harder than everyone else, etc. Yet, I think there’s a lot of truth to this advice. You can try as hard as you want, sometimes you need to wait to be ready. It doesn’t mean don’t do anything, though:

“Don’t Try” is not about embarking on a hedonistic lifestyle like Bukowski’s for the sake of it. It’s about taking time to let your creativity speak to you. It may arrive through activities and environments that make you elated, or angry, or through putting yourself in situations that are new, perhaps even uncomfortable. Or it may arrive from just sitting still and taking a break.


⚡️ Startup Stuff

🧘‍♂️ Mental Health at Startups

Here are some sobering facts:

If you are an entrepreneur, you are 50% more likely to report having a mental health condition (Michael Freeman Study). The same study revealed that founders are:

  • 2X more likely to suffer from depression

  • 6X more likely to suffer from ADHD

  • 3X more likely to suffer from substance abuse

  • 10X more likely to suffer from bipolar disorder

  • 2X more likely to have psychiatric hospitalization

  • 2X more likely to have suicidal thoughts

There are a lot of reasons for this, among them:

  • Delegating/letting go. Letting other people take over jobs you’ve been doing is a scary thing. Your startup is your baby, and you want to tell your story. You are essentially “firing” yourself from a part of your job when you hire someone, and that is frightening.

  • Balance. Founders tend to throw themselves into their work 150%, and things outside of work may fall to the wayside (relationships, health/exercise, and hobbies that bring joy). When relationships suffer, stress can manifest.

  • Fundraising. You will experience a lot of rejection and many “keep in touch” messages. Your startup is your baby, and your baby will get rejected on a regular basis. Being “on” all the time is exhausting. Managing your team and investor’s expectations is exhausting. Getting investors to move forward as a “herd” is exhausting.

We could keep going and list many more reasons, but you get the idea, being a founder is particularly hard. The first essential thing is to remove the stigma around this. We need to get rid of the idea that talking about struggles is a sign of weakness that has no place in the entrepreneurial world.

Thinking about preventing rather than curing is what motivates everything we do at lifetizr, but this preventive mindset should also be adopted for everything else. You want to be playing the long game and still be around in 20+ years. To get there, you have to find the maximum sustainable output you can deliver.

You’re obviously not going to have a 9—5 mindset (although there’s nothing wrong with that if it’s your style). Still, it would be best if you tried to listen to how you feel and be careful with things like relationships, family, etc. because some things are irreversible. Finding a group of peers also building a company, getting a coach/therapist, and putting your health first are things that can help a lot.

I’m not sure I agree 100% with Jack here, but he’s raising an interesting point.


📚 What I Read

🏋 The Sovereign Lifter

This article reignited my dream of building a home gym where I will settle. After being out of the gym for 15 months, I was recently able to return to weight training, and, to me, nothing feels better than this.

Every strength athlete knows how important consistency is to making and preserving gains. Missing a little as two weeks of training can be a major setback, especially if you're advanced. When COVID-19 came to America, many state and local governments ordered gyms to close. As cities started to lock down, lifters were forced to preserve what gains they could by doing bodyweight exercises and creating makeshift weights using random heavy objects around the house.

What I find particularly interesting is that it’s not expensive as people might think. What’s expensive is the place, if you live in a big city.

The part of a home gym that can actually be quite expensive is not the equipment, but the floor space. Cost of floor space is completely dependent on where you live. Almost no one can afford space for a decent home gym in Manhattan or San Francisco. But most people who were living in these hyper expensive places pre-COVID can now work remotely.

Finally, I welcome companies trying to bring tech to fitness, but that’s not for me. I like to keep it simple and use the time-tested ways of building strength and muscle.

☢️ Isabelle Boemeke is the Nuclear Influencer the World Needs

This is a great interview of Isabelle Boemeke, the first of, I hope, a new concept of influencers advocating for science, progress, and human excellence.

The world is currently decommissioning many nuclear plants when nuclear would be the perfect solution to curb climate change.

All energy creation comes with some degree of risk. So does energy failure. The recent freeze in Texas killed more people due to lack of electricity than the death toll at Chernobyl. When people say “I believe the science,” it tends to mean, “I believe in everyone agreeing with me.” A data model is an essay rather than an unimpeachable truth. Yet the slow, brutal devastation of fossil fuel emissions needs to be confronted. “I think we’re going to look back and ask ourselves how did we let at least five million people die from air pollution every year?” says Boemeke. “It’s totally obscene.”

For more:


🎙 Podcast Episode of the Week

The good episodes of the week:


🍭 Brain Food

🌌 The Expansion of the Universe

I found this article fascinating. It explains that if we wait too long to explore the Universe, we might never be able to do so because of the accelerating expansion of the Universe.

We can wait a while to explore the Universe, but we shouldn’t wait too long. If the Universe continues its accelerating expansion as predicted by the usual model of cosmology, it will eventually expand by a factor of 2 every 12 billion years. So if we wait too long, we can’t ever reach a distant galaxy.

In fact, after 150 billion years, all galaxies outside our Local Group will become completely inaccessible, in principle by any form of transportation not faster than light!

On a personal note, I can’t help but think that our understanding of physics will be so radically different even in a few decades from now that predictions in the far future may not make a lot of sense. It’s very hard to imagine that all of our current theories will be proven wrong at some point, but a quick look at 16th-century physics will bring you to the same conclusions. Two or three centuries of new physics with the increasing power of our tools will create a world we can’t even begin to fathom.

Still, if you want to visualize space-time exploration, this is, by far, the most amazing video I ever watched.

Another cool fact I learned this week: all planets can fit between the Earth & Moon.


🎥 What I’m Watching

🍄 How to Change Your Mind

A great exploration of Michael Pollan’s ideas and work on psychedelics. His book How to Change Your Mind is on top of my list, but I haven’t read it yet. This video is a good intro.

For more on psychedelics, I recommended The Immortality Key by Brian C. Muraresku a few months ago in the newsletter. It’s an exceptional explanation of how ancient psychedelics rituals led to today’s religions.


🔧 The Tool of the Week

🤽‍♂️ Poolside FM

The sunny days are back. It’s time for Poolside FM to make a comeback on the newsletter. I got bored of Endel this week and wanted something on a different note. I naturally went back to Poolside FM to get the right soundtrack during my working hours.


🪐 Quote I'm Pondering

Feeling insignificant because the universe is large has exactly the same logic as feeling inadequate for not being a cow. Or a herd of cows. The universe is not there to overwhelm us; it is our home, and our resource. The bigger the better.

David Deutsch


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👋 EndNote

Thanks for reading!

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Until next week,

Mehdi Yacoubi

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