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From “Planning the Execution” to “Executing the Plan”: 2024 Q1

As most of you know, I’m on a mission to help Humanity defeat aging by 2060. This is a bold, even unreasonable lifetime commitment. In order to maximise the odds of success, the very least is to find like minded people and execute seamlessly toward our common goal. Here I’m elaborating what has been achieved during the 1st Quarter of 2024, the failures and also what I’ve learned along the way.

The action plan

To summarize the overall structure, the plan is to build from the ground up a 3 layer ecosystem (from the top to the bottom):

– Layer 1: the “2060 Foundation”, whose purpose is to work on “longevity oriented” long term initiatives, such as fundamental R&D, federating the ecosystem, public and political advocacy.

– Layer 2: the “Longevity Startup Studio”, whose purpose is to generate profit through the creation of successful startups in the longevity space (both biotech and preventative health). The profit generated by the Startup Studio will fund the 2060 Foundation, because no matter how pure our intentions to help Humanity live longer and healthier are, nothing can be achieved without money.

– Layer 3: successful startups in the longevity space, created by the Longevity Startup Studio

The bad news is that this is a very complicated plan to put in place. The good news is that I’m not alone anymore, we’re already a small community of highly competent and motivated people who work together to make this happen.

Read below how far we’ve come in 3 months!

The 2060 foundation

– we’re roughly 100 members already, scientists, entrepreneurs, VCs, political activists, etc… all of them has specific skills, and is motivated by the same goal: defeat aging. This has been achieved with minimal to no communication or budget, which is very encouraging as to the potential of the mission to motivate a great number of people.

– we’ve created the Longevity Investment Club, federating startup founders and investors in the longevity space, and had our very first pitching session on the 5th of April, with 30 people signed up for this event.

– we’ve got serious discussions with one of the most renowed experts in longevity in the world (can’t disclose his name yet), to be part of the initiative and support our foundation. We’re working with him to build the foundation in the best possible way, with the right connections, the right advisory board, the right strategy, in order to avoid traps as much as possible.

The Longevity Startup Studio

The Longevity Startup Studio is the most complex project, but also the most promising, this is where profit will come from, this is what will create enough value for the Foundation to execute its mission:

– we’re 3 in the founding team, one of them a highly respected and successful biologist, medical doctor, and also entrepreneur in the medical field, and another one having worked with Elon Musk in one of his biotech initiatives, with a considerable expertise in venture capital.

– we have discussions for funding and partnership with the BPI France (the French Soverign Fund so to speak, responsible for funding innovation), and 2 biotech and health startup studios, who are interested by our expertise and our project.

Ikare

Ikare.ai is supposed to be the very first startup created by the Startup Studio. It’s an online service for longevity consultations, where Medical Doctors and Health Coaches with deep expertise in Longevity help patients reach a Healthspan of 100+ years:

– we already have 15 patients being assisted by our doctors and coaches in their longevity journey. Interesting point, one of the patients is a principal scientist working for one of the best funded research facility in longevity in the Bay Area (for confidentiality reasons I can’t disclose names). But it’s funny that we’re so early on, but still taking care of the longevity of one of the best longevity experts in the world 🙂

– we’re a team of 4 cofounders, one of them being Dr Denys Coester, one of the best doctors in biohacking and longevity in France

The end game for Ikare.ai:

-1 longevity medical consultation / month for every human being aged 40+ (3 billion people worldwide as of today, but the demographic dynamic will bring more and more people in this category in the next years/decades).

-an AI longevity doctor, monitoring the overall health of billions of people, and issuing recommendations on what exams to take, at what frequency, recommending what preventative measures to take to preserve their long term health. Think of it as a huge AI-driven dashboard with green, orange and red lights for each patient, monitoring, and taking care of people’s health well before any disease or symptom appear.

Failures & Lessons Learned

When working on such a complex project, if we don’t have failures along the way, it means we’re not pushing hard enough. But rest assured, we’ve had some failures along the way also:

– we’ve lost a highly selective startup competition called Wilco, because we were not able to explain the vision and the product well enough in our slides (and also apparently because the slides looked unprofessional ?!? – that one hurt me a lot, I’ve put my heart in those slides 🙂 ). Next time I’ll “test” the pitch deck on more people, make it bulletproof, and take a professional designer to create world class visuals.

– one of the most professional and important potential investors in the Startup Studio told me that I was not qualified enough to be credible as the cofounder of such a structure. It seems they only consider serial-entrepreneurs in biotech. I’ll have to work more in order to explain why I’m the right person for this job.

Stay tuned, more is coming for the Second Quarter of 2024! Thanks for following the adventure, and for some of you, even getting involved in it!

The “2060” Foundation: 40 years to change everything

I have recently created the “2060” Foundation with a small but visionary group of highly determined people: https://2060.life . Our purpose is to help Humanity defeat ageing by 2060. I describe in this article the rationale behind the creation of this Foundation, and also some details on the status and progress of the work being done by our team.

The World Today

The Modern Western Civilisation has been suffering from a chronic disease for the last 5 decades, and it’s only getting worse: it’s terrible and it’s called short-termism. It has become harder and harder to plan and execute any major long term project that spans on more than 5-10 years. We see it in Venture Capital: I’m over-simplifying, but no VC would invest in a startup having the potential to offer 1000X returns in 20 years. We see it in Politics: no politician will sponsor a project which will have results in 20 years from now, when his election term will be long gone. We see this short-termism everywhere.

There are some countries which are able to execute long term visions, and envision and plan for the future decades, such as Saudi Arabia, Arab United Emirates and China, to name a few. But winning the war against aging is one of Humanity’s biggest challenges, and need to be considered at the global scale.

The “2060” Foundation Vision

We have created 2060 to thwart short-termism: the Foundation will bear projects that promote longevity, and are not directly profitable or offer too long-term ROI horizons to make them fundable by public or private funding. We’re here to push and accelerate Humanity towards the tipping point beyond which the Longevity field will inevitably become mainstream.

We tend to overestimate what we can do in a year, and underestimate what we can do in a decade. Audacity, grit, determination and long-term resilience will pave the way towards major breakthroughs in the Longevity field. We will support all the initiatives and execute all the long-term projects that no one wants to focus on, but which are nevertheless of essence to move forward in Longevity.

“2060” is a Foundation and not a company because by definition a foundation doesn’t make profit (or the profit is reinvested by the Foundation back in Longevity projects). We want to be very explicit about the fact that our organisation is about adding years of healthy life to oneself, to the ones we love, and to Humanity as a whole, not for profit.

Thinking globally and long-term, acting locally and short-term

Having set the vision of the 2060 Foundation, we execute our plan with daily small and practical steps. No place for daydreaming! Here’s the projects we’ve started working on at the Foundation these days:

– legal paperwork for the “2060” Foundation. For now, in legal terms, “2060” is a “association loi 1901” incorporated in France, not yet a Foundation. This gives us a legal entity on the short term, until the more complex paperwork allows our Foundation to officially come into existence.

– a Longevity Investment Club. Finding Investors who understand and are interested in Longevity is still rare nowadays. Finding credible Startups and Entrepreneurs in the field is even harder. We’re gathering both groups of people around our Longevity Investment Club, to increase efficiency and transparency in the ecosystem. We want to see as many startups and investments as possible in Longevity. The Longevity Investment Club is up and running.

– a Longevity Community. We’re offering whoever wants to know more about longevity, a community of like-minded people (now Slack), with online and offline events about this fascinating topic.

– a Worldwide Longevity Network. Online presence is great, physical presence is even better. It’s not enough to meet online. The longevity community needs physical places to meet, hang out with like-minded people, do some blood tests, use some specific machines (like a DEXA scan for example, impossible to find in Marseille for example to my knowledge).

– as the team grows, and more and more people resonate with the Foundation goals, many other projects will be initiated by the Foundation during the weeks, months, years and decades to come. Stay tuned!

2060 and you

If our goal resonates with you, and you want to get involved in the Foundation, you can do a couple of things:

– sign up as an investor or entrepreneur in Longevity here, it’s free.

– sign up as a member in our foundation, and find out more about longevity and the fascinating people who push the field further every day, here

– last but not least, talk about 2060 and invite your friends to join for free

See you soon!

Rapamycin may be the first “youth pill” in the History of Medecine

Rapamycin is an immunosupressant drug, mainly used today after organ transplants. However, recently, scientists have discovered that it may have “gero-protective” properties, arguably offering between 9% and 14% of additional lifespan in humans.

The story of Rapamycin

Rapamycin is a molecule produced by a bacteria called “Streptomyces hygroscopicus”, and was first discovered in 1964, by a Canadian scientist in the Easter Island (do the mysterious staring eyes statues ring a bell?). This molecule was firsthand intriguing by its unusually strong antifungal properties.

A couple of years later, the pharmaceutical company which was financing the research, called Ayerst, closed their canadian lab, and formally requested all rapamycin cultures and extracts to be destroyed. However, one of the researchers, called Suren Sehgal, did not obey orders, and hid the samples from Easter Island in his personal fridge.

A few years later, the Sehgal’s new management team agreed to resume the research on Rapamycin. It proved useful in healing all sorts of fungal conditions (athlete’s foot, body rash, etc.), but also in partially suppressing immune reactions to organ transplant rejection (mainly kidneys and liver), for which it has been approved by the FDA (Food and Drug Administration) in 1999.

However, this is where things get really interesting: back in 2006, Rapamycin has been shown to lengthen the lifespan of eukaryotic cells, that is, cells from multi-cellular organisms such as humans (experts out there please pardon me for the extreme approximation of this definition).

Why this time it may be different

Discovering the “youth pill” has been a human obsession since the most ancient times. It has inspired myths, writers, poets, explorers, and charlatans throughout the ages. It is said that selling so-called magical “eternal youth potions” has been the 2nd oldest profession on Earth 🙂 Juan Ponce de Leon (1474 – 1521), was such an utopian explorer, who is said to have devoted his life to searching the “fountain of youth“. Of course, none of them came anywhere close to it.

Well, today, scientists have valid reasons to consider that the time has finally come for such a groundbreaking discovery. Before explaining how this molecule works in complex multi-cellular organisms, let me tell you why this time it’s different:

– Rapamycin has been tested in various animal models (yeast, worms, flies, mice) and worked in all of them, which is extremely rare for any drug. Is now being tested on primates (a short-lived monkey called “marmoset“), dogs, and even elder humans with yet to be formally confirmed but promising and encouraging results so far.

– Rapamycin “makes sense” as a gero-protective molecule, by inhibiting a specific pathway in the eukaryotic cells. This cellular mechanism appeared so early in the evolution of life on Earth, that it is common to a big proportion of life forms as of today. More on the scientific explanation below in this article.

– This is by no way a scientific proof of anything , but many world renown scientists and doctors who study the aging processes take Rapamycin and publicly admit it, even disclosing how much and frequently they take it. They’ve made their choice, decided not to wait until FDA approves it, they have “skin in the game”, they eat their own dog food 🙂

How and why Rapamycin works

Mammals have a mechanism called mTor (mammalian target of rapamycin), which works like an “organism growth manager”: when nutrients are proficient, the mTor pathway is activated, and the organism goes into “growth mode”, cells divide, the cell metabolism increases. When nutrients are scarce, mTor is inhibited, and the organisms tends to go in “survival mode”, and each cell tends to “recycle” its waste, save energy, instead of spoiling resources.

Well, what Rapamycin does, and this is why it seems to work as an anti-aging drug, is that it inhibits mTor, forcing the organism and each and every cell within it, to go into “survival” mode: less nutrients waste, more recycling, less cell division, more cell repair.

Caveats

While there are very strong reasons to consider that Ramaycin may be the first gero-protector in the History of Mankind, we need to take into account that as of today, the scientific community has not finished the work on this very promising molecule:

– studies on humans are still incomplete

– optimal posology is still unclear (how much, how frequently should one take it?)

– the FDA has not yet approved this drug as an anti-aging treatment

– this drug has some minor side-effects (called mouth ulcers, which may be easily treated however and are insignificant given the advantages)

– even if unlikely, this drug may have yet unknown adverse effects

– you cannot buy this drug without prescription, and you won’t get a prescription as an anti-agind drug in many countries (France being one of them). It seems you can buy it in Spain without prescription, but I haven’t yet investigated enough to be sure of it.

– remember that the stakes here is “only” 9% – 14% of additional lifespan, which is at the same time a lot and very little. It doesn’t prevent us all from all the other longevity measures (healthy diet, physical activity, etc …). Also, it doesn’t prevent us from pressing the pedal to the metal and discover more efficient gero-protectors, pushing the human healthspan even further.

Me?

Some people asked me if I was taking Rapamycin. Given my promise of transparency, let me share my conclusions when it comes to this drug:

– I have personally talked to many scientists and doctors from the longevity ecosystem, many of them take Rapamycin. Some of them were very convincing in explaining why. They don’t want to wait 20 years for the FDA to approve this drug, they’ll be dead by then. Surprisingly, even the most cautious of them take it, under the assumption that even if it’s not useful, at least it’s not harmful.

– Almost all the credible trials related to Rapamycin, and scientific papers, show the same positive conclusion, being published on a regular basis. Sometime in the future, the FDA will approve the treatment when it will be 99.99% certain (not sure of the exact percentage, I just want you to get the idea). Well, as more and more papers and clinical trials results get published, the certainty will go from 90% to 95%, then 99%, and so on, the whole process taking decades. As I read those papers, it’s an ongoing process, where at every step, certainty goes up. At some point, I’d take now a drug that is 99% certain, rather than wait 15 years for it to be 99.99% certain. The numbers I’m using to explain my point are imprecise, but the rationale behind it isn’t. It all comes down to a risk management problem.

– I’m not taking this drug as of now, because I want to set up a biomarker “before – after” tracking protocol, I have too much of an engineer mindset to test stuff on myself just on “believing” it might work. Measuring is an absolute necessity for me. I want to identify the right biomarkers to measure before taking Rapamycin, decide how much I’ll take and how frequently, during how much time, and after that time span I’ll measure the same biomarkers again, to see the difference. Another reason why I’m not taking it yet is that I have to find the right way to buy it, no doctor will prescribe that in France 🙂

When I’ll move forward with this drug, I’ll let you know!

The Hallmarks of Aging

Intuitively, for each one of us, aging is “when you grow old and ultimately die”. However, aging is an incredibly difficult phenomenon to define precisely, and no general consensus has yet been reached by the scientific community as to what exactly it means. Today, the best framework we have to describe and understand aging is a set of 14 biological mechanisms, called “The Hallmarks of Aging”. Addressing each one of these mechanisms is the best action plan we have today to slow down aging.

Before 2013, there was a permanent fight between scientists, in a “there can be only 1 of us” conflict, each one of them trying to prove that his theory of aging was the right one, at the detriment of the neighbour’s. However, as some theories were able to explain some observations related to aging, none was able to reasonably explain all of them. Eventually, scientists came with this “Hallmarks of Aging” framework, which encompasses the complexity of the phenomenon, and determine everyone to collaborate in good faith again to move the science of aging forward.

This article is going to be a little bit longer, first because as discussed earlier, aging is a complex phenomenon, which even if simplified to the extreme, still needs some focus and time, and secondly because this post is going to put in place the general knowledge and structure of what’s coming in the news weeks or so, as we’ll do deep dives in each one of the topics below, to illustrate the research that’s being made to address each specific hallmark of aging, and the mind-blowing breakthroughs we expect to come in the next years coming from these specific directions.

1. Telomere Attrition

Telomeres are the small bits of DNA at the end of your Chromosomes. Every time one of your cells divide, and your chromosomes within those cells are copied, these bits of non-coding DNA will shorten. After a couple of dozen of divisions, the telomeres are shortened to exhaustion, and any further cell division will end up cropping small bits of your useful DNA information.

2. Genome Instability

There are 2 main reasons why your DNA information is partially lost as you age. The first one is that when your cells divide, the copying of your DNA is indeed incredibly accurate, but not perfect. The second reasons is that throughout your life, your whole body will suffer a certain level of stress, due to internal and external factors: oxydative stress (from so called ROS – Reactive Oxydative Stress), what you eat, sun radiation, even cosmic radiation. Multiple mutations to your DNA generate dysfunctions in your body, as the cells don’t fully fulfil their roles as they should anymore.

3. Proteostasis Perturbation

Your body is a wonderful piece of chemical machinery, with literally thousands of incredibly complex processes at the cellular level, which govern how the whole system works. At the core of these processes are the proteins, which are the basic bricks of human life. How these proteins are produced, maintained in the right balance and the adequate concentrations, is paramount to the vitality and health of your body. As we age, the dynamics and concentrations of these various proteins in our body starts to dysfunction, leading to frailty, diseases and ultimately death.

4. Stem Cell Exhaustion/Degeneration

Stem cells are undifferentiated cells, similar to the ones foetuses are created from. As kids and healthy adults, we all have stem cells spread all across our bodies, which are used by our body to regenerate (as part of systemic physiological processes, as well as in case of accident). However, the proportion and quality of stem cells decreases as we age, resulting in our body being unable to properly regenerate damaged tissue anymore.

5. Epigenetic Deprogramming

It’s common knowledge nowadays, that our DNA dictates how our body works. However, DNA is just half of the story (in fact, some scientists say it’s only around 20% of the story, but more on this later). The rest of the story is that as cells differentiate from stem cells to specialized cells (such as neurons, skin cells, etc.), large portions of our DNA get silenced by a mechanism called “methylation”, and only the pertinent portions of the DNA related to the specialization of each cell are being expressed. This makes total sense, as you don’t want neuron-related portions of DNA being expressed in skin cells, for example. Well, the bad news is that as we age, this “methylation” mechanism gets chaotic. Thus, you end up having cells in certain tissues behaving as cells in other tissues. No surprise that this partial loss of cell identity ends up in a big mess 🙂

6. Altered Energy Sensing

When you’re young and in good health, your cells have a remarquable capacity to adapt to a wide range of energy and resources related situations. It senses how much oxygen you have in your blood, what the demand in terms of energy production is, how urgent and critical it is, how much glucose and insuline is in your blood, etc … As you age, the performance of the whole “energy sensing” system decreases, with cells taking the wrong decisions as to how much energy to produce and what to do with it, which leads to dysfunctional mechanisms (as for example insuline resistance, related to Diabetes).

7. Altered Intercellular Communication

Cells communicate with each other, and it has even been recently discovered, as incredible as it may sound, that in extreme situations, “better off” cells will create nano-bridges/nano-tubes to connect with other stressed cells, to send them parts (such as mitochondria) and nutrients, to prevent them from dying. As we age, this communication is more and more disturbed. Not only cells don’t help each other anymore, but stress signals emitted by certain cells end up contaminating the cells around them, in a snowball effect.

8. Cellular Senescence

Cells are meant to fulfil a certain function, and reproduce as part of the natural regeneration tissue flow. However, when the DNA baggage of a certain cell is damaged or the overall disorder in that cell goes beyond a certain threshold, this leads either to cell death (called apoptosis), either to cell senescence, which may also be remembered as “zombie mode”: the cell is not dead, but is not working properly anymore, is not dividing anymore. Therefore, not only does it use resources at the detriment of other healthy cells, but it also sends negative signals to its proximity, contaminating other cells and turning them into zombie cells as well.

9. Mitochondrial Dysfunction

Mitochondria are the energy production factories of our cells. In short, they eat up glucose, and turn it into another product called ATP, which is used as energy currency in the cell. As we age, there are fewer mitochondria, and their quality is also lower, and without proper levels of energy, the maintenance processes of our cells are heavily impacted.

10. Compromised Autophagy

When cells don’t have enough energy, it may actually be a good thing (more on this in future posts). In those situations, cells turn into a particular mode where they’ll recycle and clean up accumulated toxines and unused reserves. This is positive, as these unused waste is at risk to clutter the cells, and increase the disorder in their processes. Well, as we age, autophagy does not work properly anymore, so the damaded parts of the cell don’t get recycled anymore.

11. Microbiome Disturbance

The Microbiome is the whole bacteria and other micro-organism ecosystem, which lives in symbiosis with your body, and is located in your gut. The nature of these micro-organisms, and how they interact with your gut, is closely related to your health: digestive diseases come from microbiome problems, even neuro-degenerative diseases seem to be related to it. Recent studies seem to suggest that as we age, the microbiome changes also, leading to our food being less well decomposed into basic nutrients for our body.

12. Inflammation (also called inflamm-aging – no pun intended)

Inflammation is the way our body reacts to agression. It is a healthy and essential part of how our body protects itself from pathogens. When it’s “business as usual”, you get a wound, a disease, and then that part of your body will swell, 2 hormones proper to inflammation are produced – bradykinin and histamine – and everything is set up for recovery. However, as we age, the inflammation may become permanent (chronic), leading to exhaustion of your immune system. In addition to this, your immune system gets disoriented, and starts attacking healthy cells, further affecting the overall functions of the affected tissues.

13. Altered Mechanical Properties

Our cells do not just plainly “stick” together by themselves. They’re placed in “collagen complexes”, that come in many shape and sizes, which form the basic “scallfolding” structures for our bodies. For example, the degradation of our collagen structure accounts for our skin being less and less flexible as we age, and wrinkles appearing on our faces. Collagen is produced by a specific category of cells called fibroblasts. Well, chaotic collagen creation and preservation generates not only aesthetic discomfort, but also functional damage, in our bones, our muscles, heart, etc.

14. Splicing Dysregulation

Splicing is the process by which the DNA gets transcripted into mRNA. In order to understand it, let’s get back to basics (remember your high school biology classes). Your DNA lies within the nucleus of your cells. When your cell needs to create a protein, the first step is to unfold the DNA from the chromosomes, and to copy the portion of relevant DNA in the form of mRNA, which is then sent outside the nucleus of the cell, to manage the creation of that protein. The process by which DNA is turned into mRNA is called the transcription. However, the mRNA is not an exact replica of the relevant DNA. Before it is sent outside the nucleus of the cell, it suffers a process called “splicing”, which consists of cutting portions of the copied DNA, and linking them back together. Well, this process of “splicing” works less well in old cells.

Tadaaaaaa, this is it! Now you have the big picture of what’s going on in your body as you age, and also what the scientific community is working on as I write this, in their laboratories!