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:
In this episode, we explore:
Let’s dive in!
As longevity is becoming mainstream, many discussions around the optimal diets and supplements to promote healthspan & lifespan started popping out.
This review is an interesting effort at separating the facts from fiction.
Background
Reduced caloric intake without malnutrition is the oldest known life span–extending intervention. Laboratory studies throughout the 20th century established and confirmed the benefits of caloric restriction (CR) in multiple model systems. CR not only increased life span across evolutionarily distant organisms but also reduced age-associated disease burden and functional decline in these studies. Epidemiological data from human populations is also generally consistent with the idea that lower caloric intake is associated with increased life expectancy. In recent years, numerous diet modalities that are purported to be “antiaging” have sprung from these observations. These diets restrict particular macronutrients (carbohydrates or protein) or feeding intervals and can be divided into those that impose reduced caloric intake versus those that are isocaloric to control diets.
Advances
We evaluated several of the most popular antiaging diets, including CR, intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and essential amino acid restriction. By characterizing these nutritional interventions in comparison with classical CR, we gained numerous insights. Many studies fail to control for reduced caloric intake in the diet group, making their effects impossible to decouple from CR. Although often presented as uniformly beneficial, the effects of CR on life span are highly dependent on genotype and, in some cases, cause reduced survival. Despite their limitations, these studies have greatly improved our understanding of the cellular response to low nutrient availability. A picture is beginning to emerge of a complex network composed of multiple signaling pathways that converge on key molecular hubs; foremost among these is the mechanistic target of rapamycin (mTOR). Because mTOR and other components of this network are well-studied drug targets, there continues to be considerable interest in pharmacologically targeting this network to increase longevity and health span. Human studies, both correlative and controlled, are consistent with health benefits conferred by a CR diet. However, it remains unresolved whether these benefits are a consequence of modulating the aging process itself or are simply the result of avoiding obesity. Several unresolved questions suggest caution when considering whether to recommend or implement any of these diets among the healthy general public. Among these is understanding how genetic and environmental variation modify diet response, especially in understudied populations and in the context of environmental challenges such as, for example, a global viral pandemic.
Outlook
CR and other antiaging diets have yielded important insights into the complex and evolutionarily conserved signaling pathways that transduce information regarding environmental nutrient availability into a physiological response to promote healthy longevity. This understanding, in turn, has opened the door to a new generation of longevity-promoting interventions that mimic molecular responses to nutrient deprivation. Although CR and other diets hold promise, additional data from carefully controlled studies is needed before broadly recommending or implementing these diets, or other interventions, for otherwise healthy people. Human genetic and environmental variation combined with the challenge of modeling human aging in ultimately dissimilar mammalian model systems pose fundamental limitations to our current ability to predictably translate these findings to people. From a pragmatic perspective, even if these challenges can be overcome, widespread adoption of dietary interventions for healthy longevity seem unrealistic. We therefore suggest that alternative, nondietary strategies with the potential for public uptake should therefore be pursued. In particular, validated biomarkers of biological aging are required to match intervention to each person’s distinct genetic and environmental context and thereby optimize individual healthy life span. Future research directed at clarifying the underlying mechanisms involved in eliciting the longevity-promoting response to CR, and how this differs among individuals, should one day help us realize a true precision geroscience approach.
Abstract
Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative “antiaging” diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids. Despite mainstream popularization of some of these diets, many questions remain about their efficacy outside of a laboratory setting. Studies of these interventions support at least partially overlapping mechanisms of action and provide insights into what appear to be highly conserved mechanisms of biological aging.
On a personal level, I became less and less focused on nutrition as soon as I found the basics that worked for me.
Getting enough protein (1g per lb of bodyweight if you’re lifting weights)
Getting adequate calories to fuel training
Eating my last meal 3+ hours before bed not to interfere with sleep (not easy to do every day)
Mostly whole foods, minimal highly processed ingredients
This might not be the perfect diet, but I think a lot of the efforts to find to so-called “perfect” protocol/ diet/ routine is wasted time that could be invested in mastering the basics of the other health pillars. I’d rather invest that time trying to become a strength athlete or something else.
On top of that, I find that obsessing about yourself too much leads to negative results in other aspects of life, from being too self-centered and not flexible. The sweet spot between extreme optimization and going with the flow & being less controlling is hard to find but might bring the best of both worlds.
It’s the perfect time of the year to re-share this excellent article by Clayton M. Christensen.
Create a Strategy for Your Life
A theory that is helpful in answering the second question—How can I ensure that my relationship with my family proves to be an enduring source of happiness?—concerns how strategy is defined and implemented. Its primary insight is that a company’s strategy is determined by the types of initiatives that management invests in. If a company’s resource allocation process is not managed masterfully, what emerges from it can be very different from what management intended. Because companies’ decision-making systems are designed to steer investments to initiatives that offer the most tangible and immediate returns, companies shortchange investments in initiatives that are crucial to their long-term strategies.
Over the years I’ve watched the fates of my HBS classmates from 1979 unfold; I’ve seen more and more of them come to reunions unhappy, divorced, and alienated from their children. I can guarantee you that not a single one of them graduated with the deliberate strategy of getting divorced and raising children who would become estranged from them. And yet a shocking number of them implemented that strategy. The reason? They didn’t keep the purpose of their lives front and center as they decided how to spend their time, talents, and energy.
It’s quite startling that a significant fraction of the 900 students that HBS draws each year from the world’s best have given little thought to the purpose of their lives. I tell the students that HBS might be one of their last chances to reflect deeply on that question. If they think that they’ll have more time and energy to reflect later, they’re nuts, because life only gets more demanding: You take on a mortgage; you’re working 70 hours a week; you have a spouse and children.
For me, having a clear purpose in my life has been essential. But it was something I had to think long and hard about before I understood it. When I was a Rhodes scholar, I was in a very demanding academic program, trying to cram an extra year’s worth of work into my time at Oxford. I decided to spend an hour every night reading, thinking, and praying about why God put me on this earth. That was a very challenging commitment to keep, because every hour I spent doing that, I wasn’t studying applied econometrics. I was conflicted about whether I could really afford to take that time away from my studies, but I stuck with it—and ultimately figured out the purpose of my life.
Had I instead spent that hour each day learning the latest techniques for mastering the problems of autocorrelation in regression analysis, I would have badly misspent my life. I apply the tools of econometrics a few times a year, but I apply my knowledge of the purpose of my life every day. It’s the single most useful thing I’ve ever learned. I promise my students that if they take the time to figure out their life purpose, they’ll look back on it as the most important thing they discovered at HBS. If they don’t figure it out, they will just sail off without a rudder and get buffeted in the very rough seas of life. Clarity about their purpose will trump knowledge of activity-based costing, balanced scorecards, core competence, disruptive innovation, the four Ps, and the five forces.
My purpose grew out of my religious faith, but faith isn’t the only thing that gives people direction. For example, one of my former students decided that his purpose was to bring honesty and economic prosperity to his country and to raise children who were as capably committed to this cause, and to each other, as he was. His purpose is focused on family and others—as mine is.
The choice and successful pursuit of a profession is but one tool for achieving your purpose. But without a purpose, life can become hollow.
I greatly enjoyed this piece on signaling and imitating high-status people.
This tendency to over-imitate high status people is why there is (was?) a peculiar interest in the morning routines of successful people. A few years ago there were a lot of articles and interviews about how some CEO or billionaire would wake up at a certain time, enumerating the newspapers and books and blogs they read, what they ate for breakfast, what their morning exercise routine was like, and so on. No one wants to read about grueling 100 hour work weeks and all the associated stress and anxiety and doubt. Plus, articles about books, newspapers, and exercise routines helps keep the consumer machine going. Forget about hard work. This CEO reads these titles on innovation and leadership and takes these cutting-edge anti-aging pills (a form of advertisement to the reader).
It’s wise to exercise caution before imitating the personal habits of prestigious people. Drinking the same green breakfast smoothie as your favorite entrepreneur or podcaster probably isn’t going to do much for your own success, but the human impulse to over-imitate still wonders.
The critical idea is that imitating very high-status people can backfire because they are often engaged in counter-signaling, and that works only if you’re already high-status. Think about extreme humility, arriving late to social events, dressing down, not promoting your work, etc.
A better strategy is to imitate people just a few steps ahead of you.
Successful Americans no longer feel the need to signal. So they now demonstrate their status through countersignaling. Other cultures still practice straightforward signaling.
Returning to the level of the individual, if you are trying to level up, the best approach is to borrow the strategies of those a little ahead of you—people who are still signaling. Beware of imitating those who are so far ahead that they can afford to countersignal.
If you are relatively early on your path, it is natural to seek advice from those who have achieved astounding success in your area of interest. You’d be better off, though, asking people who are on a similar trajectory as yourself, but a little further ahead. If you’re a white belt and want to level up, don’t ask the black belt (or red belt) what to do. Ask the purple belt.
A good reminder, especially when hiring.
Pair with: Hire People Who Give a Sh*t
New Goggins book means we stop everything we’re currently reading, and we read/ listen to that instead 😂 (half joking here.)
Can’t Hurt Me is one of the best books I have ever read. So I couldn’t wait to read the second Goggins book!
This is not a self-help book. It’s a wake-up call!
Can’t Hurt Me, David Goggins’ smash hit memoir, demonstrated how much untapped ability we all have but was merely an introduction to the power of the mind. In Never Finished, Goggins takes you inside his Mental Lab, where he developed the philosophy, psychology, and strategies that enabled him to learn that what he thought was his limit was only his beginning and that the quest for greatness is unending.
The stories and lessons in this raw, revealing, unflinching memoir offer the listener a blueprint they can use to climb from the bottom of the barrel into a whole new stratosphere that once seemed unattainable. Whether you feel off-course in life, are looking to maximize your potential or drain your soul to break through your so-called glass ceiling, this is the only book you will ever need.
Pair with: #1906 - David Goggins
Falling productivity is a bad sign for the tech industry, and QE was a big mistake
Degrowth needs to die
It never ceases to amaze me how many stupid ideas manage to catch on and get dressed up with some really big, fancy, meaningless words. I get we all have different values and priorities, but it seems we should all agree economic growth is a really good thing. It is singularly responsible for relieving us from hard labor, the decline in poverty, an increase in living standards, and longer, healthier lives.
And yet, there is actually a viable degrowth movement. And I don’t just mean people shutting down highways and gluing themselves to famous paintings. I’d lump the “we need equal outcomes” and anti-globalization people in with degrowthers, and they have a mainstream presence in both parties of our government. I think they are well-intentioned, but where they go wrong is their belief that the global economy is zero-sum. They think if someone got richer, it’s because someone else got poorer. If the economy grows, it must come at the expense of the environment.
I’ve been an economist for a long time. And one thing that is central to economic thinking is seeing the economy as non-zero-sum. If you innovate and make the world more productive, everyone will be better off, and over time, humanity has thrived because of growth. And you can grow using fewer resources, which is good for the environment.
Contrasting the signaling styles of old elites vs. new elites.
From economic to cultural capital
Elites used to distinguish themselves by what they consumed. Sociologist Thorstein Veblen wrote about how the wealthy bought silver spoons even though they weren't more useful than regular spoons — they were purely a sign of status.
The fact that these goods were expensive and useless is what made them high status, since only wealthy people could buy them. Expensive watches and fancy purses serve the same purpose today.
But over time, manufacturing improvements made goods like silver spoons much cheaper and thus accessible to a wider audience. This meant they were no longer reliable status indicators. As a result, elites stopped buying material goods as much and instead pursued more durable forms of status: what French sociologist Pierre Bourdieu called “cultural capital”
Cultural capital is a collection of a distinctive aesthetics, skills and knowledge usually obtained through education and pedigree: how you speak, dress, and what you read and watch.
Cultural capital is what unifies the poor adjunct professor and the rich lawyer. More importantly though, cultural capital is what separates both of them from the highly-paid plumber without cultural capital. The highly-paid plumber won’t be in the same class as the former two even if he makes much more money than the poor adjunct professor.
Cultural capital came to supplant financial capital as the currency of class mobility. Anyone can accidentally get rich, the logic goes, but it takes years to acquire cultural capital.
Another way of describing this shift is from conspicuous consumption to both inconspicuous consumption and conspicuous production.
Pair with: Status as a Service & Signaling as a Service
I loved this piece about two sailors. One focused on what he wanted, and the other focused on what people thought of him.
The two men, Donald Crowhurst and Bernard Moitessier, are astounding examples of how the quality of your life is shaped by whom you want to impress. Their stories are extreme, but what they dealt with was just a magnified version of what ordinary people face all the time, and likely something you’re facing right now.
Donald Crowhurst was a tinkerer who came up with his own boat modifications. Convinced his innovations could propel him to win the Sunday Times race, he faced just one obstacle: he was broke, and stood no chance of financing the race himself.
Crowhurst struck a deal with an English businessman who agreed to cover the cost of the race under two conditions: They would orchestrate a media frenzy, portraying Crowhurst as a sailing savant. And if Crowhurst didn’t finish, he would owe all the money back.
It’s crazy to see how the same situation can be perceived so differently depending on your inner motivations.
The personality required to spend nine months alone at sea selects people who are fine detaching from society. Moitessier was an extreme version of that, and the idea of sailing for someone else’s pleasure – to perform for the press, the race organizers, the sailing magazines, the fans – was so detestable that midway through his voyage he’d had enough.
He wrote in his diary:
I really feel sick at the thought of getting back to Europe, back to the snakepit … I am really fed up with false gods, always lying in wait, spider-like, eating our liver, sucking our marrow. I charge the modern world – that’s the Monster, trampling the soul of men … returning to [England] feels like returning to nowhere.
But being on his boat, Joshua, was a different story. He loved it, loved being on the water. Moitessier later recalled:
There were so many beautiful days on this beautiful boat that it really made time change dimensions … I was just feeling totally alive. And that was just fantastic.
The conclusion is important to remember:
But their outcomes seemed to center on the fact that Crowhurst was addicted to what other people thought of his accomplishments, while Moitessier was disgusted by them. One lived for external benchmarks, the other only cared about internal measures of happiness.
They are the most extreme examples you can imagine. But their stories are important because ordinary people so often struggle to find balance between external and internal measures of success.
I have no idea how to find the perfect balance between internal and external benchmarks. But I know there’s a strong social pull toward external measures – chasing a path someone else set, whether you enjoy it or not. Social media makes it ten times more powerful. But I also know there’s a strong natural desire for internal measures – being independent, following your quirky habits, and doing what you want, when you want, with whom you want. That’s what people actually want.
Mind-blowing video from the creators of Journey to the End of Time.
I have no idea whether these ideas will be proven right or wrong, but I find them entertaining, and I like Hancock’s outside-the-box thinking (which seems harder and harder lately).
I experimented with magnesium to improve my sleep but got mixed results. Next, I’m trying Glycine. I got good feedback on this brand. As always, I’m sharing my self-experiments and progress on Vital.
“Life is a mountain of solvable problems, and I enjoy that.”
— James Dyson
Thanks for reading!
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Until next week,
Mehdi Yacoubi
