What’s New?

A billionaire's ambition to feel biologically 18 when he turns 50 certainly garners significant media attention.

Why Does This Matter?

The aspiration to conquer aging and evade death encounters two fundamental laws of nature, which are often overlooked by billionaires. Attempting to defy these laws is futile, yet adapting to them can greatly enhance the aging experience.

What Comes Next?

You, too, can challenge the billionaires. This scientist’s personal experiences and research provide initial evidence, not of a mythical fountain of youth, but of achieving a vibrant older age at a fraction of the billionaires’ costs.

“It’s more than just a joke when I say that Jesus Christ is my main rival.”

Tech mogul Bryan Johnson dismisses the idea that death is an inevitable end, viewing it instead as a solvable problem. His motto, “Don’t Die,” encapsulates his desire to halt the aging process.

If you’re questioning whether we’re part of a Monty Python sequel, you’re not alone. The resemblance in names is certainly amusing.

Given the fascination with billionaires’ eccentricities, let’s delve into their latest obsession: biohacking aging. Bryan Johnson's “Project Blueprint” stands out as the most transparent self-experimentation effort in this realm. Before we explore that, let’s clarify what ‘biohacking’ entails.

Biohacking — A Trendy Term for a Common Practice

Hackers typically seek access to a system they don’t understand, probing until they manipulate it to their advantage.

Engaging in varied exercise intensities to boost sprint performance? That’s biohacking. Experimenting with beetroot juice to manage blood pressure? You guessed it — biohacking. Adjusting protein intake for optimal muscle gain? Biohacking again.

That’s what everyday individuals do.

Billionaires, however, think on a grander scale. Why not eliminate the entire process of aging and dying altogether?

For individuals like Bryan Johnson, the human body is just as hackable as any other system.

The Life of Bryan

After selling his internet start-up Braintree to PayPal for $800 million in 2013, he began to question why he couldn’t trust his “unreliable brain” to make healthy lifestyle choices.

Overindulgence had caused him to gain 25 kilograms, compounded by his struggle with depression.

To address this, he opted to delegate control to artificial intelligence.

Project Blueprint involves an AI algorithm dictating his lifestyle decisions, while a team of 30 experts and various monitoring devices constantly track his bodily functions.

As a result, Bryan rises at 4:30 AM, follows tailored workout routines, and maintains a strict meal schedule of three daily meals, two of which are identical.

He dines by 11 AM, takes over 100 supplements each day, and retires by 8:30 PM — alone, of course.

Additionally, he utilizes a device to monitor the frequency and strength of his nightly erections.

Each month, he undergoes a series of routine medical tests, including full-body MRIs. By 2030, he aims to feel biologically 18, believing he will have successfully halted his aging.

Bryan is notably transparent with his methods, sharing a detailed list of supplements on his website.

Spoiler alert: Not all of these are accessible to the general public. Acarbose, Metformin, and Rapamycin require prescriptions. However, having a few hundred million dollars in your bank account helps.

Here’s a list of the supplements and their current Amazon prices:

I can imagine your thoughts right now:

“Alright, I’m in. If I can maintain this for the next millennium, life will be exhilarating.”

I hate to burst that bubble, but I genuinely doubt that any of this will make Bryan the first 120-year-old athlete competing against individuals 80 to 100 years younger.

After all, isn’t the goal to remain as fit and capable as a 20-year-old?

Two Fundamental Laws Will Challenge Bryan's Efforts

When it comes to aging, two natural laws are universally applicable, even to billionaires.

The first is the second law of thermodynamics, which involves entropy.

Before you disengage, stay with me. I understand that entropy can be a dry topic in physics, but it doesn’t have to be. Forget the disarray metaphor and the other confusing aspects. I promise to simplify it in a way that will leave you wondering why it seemed so complicated.

The second law is even more intriguing. It states that the whole is greater than the sum of its parts, originating from the study of complex systems.

I will explain how this relates to your rejuvenation efforts, why modern medicine’s indifference to it hampers health, and how you can address it. And yes, this law also has a name: emergence.

So, prepare to impress your next dinner guest with a discussion on entropy and emergence, without putting them to sleep.

The Party Pooper Called Entropy

According to the second law of thermodynamics, every living system inevitably experiences progressive functional decline until total functional loss (death).

This decline is termed entropy, manifesting in human biology as an accumulation of senescent cells. Think of them as non-functioning “zombie” cells that linger and cause trouble.

I’ve elaborated on this topic in more detail at the end of this post and in an international journal.

Living systems possess unique repair mechanisms that help mitigate some entropy, replacing or recycling those aging cells and their remnants. While this reduces entropy, it can never completely eliminate it, as the repair systems themselves are also subject to the second law.

“If you accept this brief explanation of entropy, great. If not, I’ve included an Easy Entropy Primer at the end of this post.”

Whatever Bryan does to his body aims to optimize these repair systems and slow decay. Allowing an AI algorithm to manage that process is akin to letting AI design an airplane. It may excel at aerodynamics, but it cannot overcome gravity.

That’s why Bryan's billionaire peers are pursuing a different approach. They aim to replace all senescent cells and the debris that entropy leaves behind. This endeavor will lead to another hurdle.

The Unpredictability of Complex Systems

Most of medical science operates on the premise that by comprehending the smallest components of our bodies—molecules and cells—we can manipulate the entire organism. This reductionist approach in medicine and science often falls short.

Out of ten molecules that show promise in preclinical research, at most one makes it to pharmacy shelves. The other nine fail during the transition from phase 1 to phase 3 clinical trials.

A prime example is the drug torcetrapib. Pfizer developed it to elevate HDL cholesterol (the so-called good cholesterol), believing that increasing HDL would effectively prevent heart attacks in at-risk individuals.

On November 30, 2006, Pfizer’s CEO, Jeff Kindler, proclaimed that this molecule would be “one of the most important compounds of our generation.”

Just two days later, Pfizer halted the trial, withdrew the drug, and acknowledged that, despite a significant increase in HDL levels, heart attacks surged by 60% in the intervention group compared to the placebo group.

The relatively new field of complex systems science terms this phenomenon emergence.

It describes when a complex system demonstrates properties or behaviors that are unpredictable and unexplainable by merely analyzing its individual components. This characteristic is a defining trait of every complex system.

A system is deemed complex when it consists of multiple interconnected parts (nodes) that interact within networks to yield a functional output.

To clarify, a Boeing 747 is complicated, not complex. Your mother-in-law, however, is indeed complex (and potentially complicated?), but you likely know this by now.

Two fascinating traits characterize complex living systems:

1. The more complex they are, the more resilient their defense against functional failure becomes.
2. What enhances their resilience also renders it impossible to predict the outcomes when one interferes with various nodes (molecules, cells, tissues, or organs).

How the Billionaires Miss the Mark

The human body is extraordinarily complex. Yet billionaires mistakenly believe they can make unpredictable interventions without falling into the trap of reductionist research that dominates medicine.

Since gerontologists identified 11 molecular and cellular hallmarks of aging, billionaires have attacked them with reckless abandon. In particular, eliminating senescent cells is at the top of their agenda.

Aubrey de Grey, a leading figure in this field and founder of the Strategies for Engineered Negligible Senescence Foundation (SENS), stated,

“The first person to live to 1,000 might be 60 already.”

He claimed that rejuvenation would be achieved in mice within a decade and in humans within another decade.

Spoiler alert: he made that statement in 2004.

Today, not a single aspect of the project has shown success in mice, let alone in humans.

To his credit, 14 years later, Dr. de Grey adjusted his timeline. The fully rejuvenated mouse model is expected to be available in another 10 years (2028) and for humans in “Fifteen years from that point.”

We shall see, but as with torcetrapib, addressing one seemingly evident issue (low HDL) might lead to the opposite effect (more heart attacks instead of fewer).

Nothing in Biology is All Bad or All Good

Replacing senescent vascular cells in aging mice not only failed to rejuvenate their blood vessels but also accelerated aging and led to earlier deaths.

Senescence, like many biological phenomena, is not entirely negative. It plays a crucial role in embryo development and wound healing. The immune system tags cancerous cells for senescence before they can progress into a cancer issue.

Evolution has had millions of years to refine how our bodies deal with entropy, developing ingenious methods to incorporate some senescent cells for self-preservation.

While I’m not opposed to the billionaires’ research initiatives, I find them intriguing and believe they will uncover ways to make aging a more enjoyable experience for many.

However, I am equally convinced that today’s individuals over 40 are unlikely to see substantial benefits from this line of inquiry.

This is why my team and I are pursuing a more practical and realistic strategy that allows everyday people to challenge billionaires.

DIY Lifestyle Medicine

Think of it as biohacking for the average person. It’s a method of transforming oneself into a clinical trial, experimenting with whatever has shown potential in research.

Naturally, healthcare bureaucrats disapprove of this idea. However, I view it as entirely legitimate.

A healthcare system that acknowledges its recommendations may be effective for some, ineffective for many, and even harmful for a few, must also accept that we “test drive” these health recommendations.

Here’s how my family and I are currently faring. None of us take medication or have any conditions requiring it.

In contrast to the reductionist approach, we treat the human body as a black box. Each individual has their own unique black box, distinct from anyone else’s.

We don’t need to grasp its molecular mechanics to “poke” it with lifestyle interventions (different exercise routines, supplements, diets, etc.). We also incorporate two additional features: We monitor the effects of our interventions on biological aging and analyze the data using a method (N-of-1) that turns an individual into a clinical trial.

My team has created an algorithm that translates pulse wave velocity data (PWV) into biological age and aging rate. PWV measures how quickly the pressure wave travels through the arterial system.

I’ve discussed the rationale for using PWV in relation to the Early Vascular Aging syndrome (EVA) and its ideal counterpart — Supernormal Vascular Aging (SUPERNOVA). You can even download an Excel file from this post to calculate your biological age using different methods.

The N-of-1 method refers to a clinical trial involving only one participant. It is the FDA- and EMA-recognized gold standard for single-case clinical experiments.

I’ve explored this method in detail in another post. Why medical practice continues to ignore it remains a mystery to me.

In brief: in the N-of-1 study design, a single subject serves as their own clinical trial, acting as both the control and intervention “group.”

The quality and significance of an N-of-1 study depend on the frequent (typically daily) measurement of a relevant biomarker (e.g., vascular aging rate) during successive control and treatment phases (AB phases; A = placebo, B = active treatment), each lasting several days or weeks.

Special statistical methods can then determine the effectiveness of the intervention and its magnitude.

My team and I have operationalized this method for laypersons. No statistical expertise is necessary.

Here's the kicker: You don’t need a billionaire’s wealth to afford this. The only tool required for PWV measurement is the Withings Body Cardio scale, which costs around $150 to $190. Coincidentally, it’s the same scale that Bryan uses.

To clarify: I have no commercial ties with Withings. I utilize their scale for my clients and research because it’s the only accessible technology for measuring PWV, and it has been independently validated.

Of course, I have access to clinical devices in my lab, but they are too expensive and cumbersome for general use.

Compare that cost to the roughly $900 Bryan spends each month just on the over 40 supplements and medications he consumes daily.

Here’s his perspective:

“I suspect that in about 60 years, we will see the first individuals who achieve immortality.”

We shall see.

Until then, I’m eager to compare Bryan’s biological status and age in 20 years, when he will be my current age.

If he surpasses me, my wife, and my son in the race to stay youthful, so be it. If you want to join this competition, let me know, and I’ll gladly include you in our ongoing trial.

For now, Bryan faces a formidable challenge. The last time I checked, his “main rival,” Jesus, had a few billion more followers than he does. But who knows? Even Jesus started small.

Easy Primer on Entropy

Imagine a small organ composed of 10 cells, numbered from 1 to 10. Let’s say this organ regulates your blood pressure. It can exist in one of two states — functional or dysfunctional. We’ll label these states as the two macrostates.

Each of the organ’s 10 cells can also be in one of two states — juvenile (fully functional) or senescent (the cellular equivalent of aging). As long as at least 6 of its cells remain juvenile, the organ is in the functional macrostate.

Let’s explore how many different configurations can lead to this functional macrostate.

There’s only one configuration for all 10 cells being juvenile. With one cell in the senescent state, there are 10 possible configurations. For a setup with eight juvenile cells and two senescent ones, there are 45 configurations. Lastly, for a 6-to-4 split, there are 210 configurations. Substitute “number of configurations” with entropy. That’s the essence of it. Entropy represents the possible configurations (or microstates) that yield the same macrostate.

Consider this: of the countless chemical reactions occurring in our cells every minute, some inevitably go awry. This is why cells cannot maintain perfect condition indefinitely, leading to an increasing number of cells transitioning from juvenile to senescent. The diminishing distance to the point of system failure (death) is known as the entropy reserve.

Therefore, the second law of thermodynamics asserts that in any system, including this tiny organ, entropy can only increase, never decrease or remain constant. Entropy reflects a system’s level of decay — an unavoidable phenomenon, much like gravity. Believing in gravity won’t spare you from its effects.

Fortunately, we possess repair mechanisms that export entropy away from the system and into the environment, replacing senescent cells with new ones.

However, these repair systems are also governed by the second law, which means they can only delay, not prevent, the inevitable decay and demise of the body.

Cited References

[1] Kraushaar LE, Bauer P. Heart Lung Circ 2021.

[2] Wong CH, et al. Biostatistics 2019;20:273–86.

[3] Honey K. J Clin Invest 2007;117:282.

[4] Cohen AA, et al. Nat Aging 2022;2:580–91.

[5] López-Otín C, et al. Cell 2023;186:243–78.

[6] BBC NEWS | UK | “We will be able to live to 1,000” n.d. http://news.bbc.co.uk/2/hi/uk_news/4003063.stm.

[7] Living to 1,000: The man who says science will soon defeat ageing n.d. https://www.cambridgeindependent.co.uk/business/living-to-1-000-the-man-who-says-science-will-soon-defeat-ageing-9050845/.

[8] Grosse L, et al. Cell Metab 2020;32:87–99.e6.

[9] European Medicines Association. Guideline on Clinical Trials in Small Populations. 2006.

[10] Nikles J, et al. Contemp Clin Trials Commun 2021;23:100826.