Why I’m getting my DNA sequenced (part 1)

One of the powerful aspects (the most powerful?) of Medicine 3.0 is to use top notch technologies to provide us with valuable, easily accessible, cost efficient, and precise data about our health. Among the many tools allowing us to do that, DNA sequencing is of essence. This article analyses why and how to leverage DNA sequencing to maximise your healthspan.


The (his)story of human DNA sequencing

It’s always difficult to spot the exact chain of events that lead to a scientific breakthrough. The story arguably starts back in 1953, when Crick, Watson, Franklin and Wilkins discover the DNA helix (3 of them receive the Nobel price for this incredible discovery – Crick, Watson and Wilkins). It eventually culminated with the Human Genome Project which started in 1990, and took 13 years, until 2003, when the first Human Genome was sequenced, for a whooping budget of approximately $3 billion, under the leadership of a biotech entrepreneur called Craig Venter, and announced with a lot of media hype by the then President of the United States, Bill Clinton (ahead of time in 2000, 3 years before the final confirmation).

Since then, the process of human DNA sequencing has significantly increased in quality and reliability, and decreased in cost to a couple of hundreds of dollars (see below).

Source here: https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data

This evolution opened the door to a whole universe of possibilities when it comes to Medicine 3.0 healthcare.

Why I’m getting my DNA sequenced and why you should too

Sequencing your DNA is important because it gives you insights into specific risk factors (but also eventual strengths you may have) when it comes to your long term health. You can do many things to increase the likelyhood of you living 100 years or more in good health, but there’s so much on your plate that you won’t be able to do it all (and by the way, even if you could, it may turn your life into a nightmare), so you need to prioritize & optimize your efforts, to focus on the most important aspects. Remember my previous article, the strategy here is to find the weakest aspects of your health (the limiting factors), and to work harder on these (and eventually ignore the aspects where you have a strong family history and low risk).

Here’s a non-exhaustive list of DNA genes and alleles that you want to look at (there’s many more, as you can imagine, and new ones being discovered every year, but the purpose here is just to give you some examples):

– APOE is a gene responsible for creating lipo-proteins which transport fats in your body, and it’s strongly associated with neuro-degenerative diseases There’s 4 alleles in humans, e2, e3 and e4: e2 give you low neuro-degenerative risk, e3 is neutral, and e4 is associated with the highest risk. Since you have 2 versions of the same gene (one from your mother, one from you father), you want to know what are the 2 versions you have in your body, 2 x e2 being the best, 2 x e4 being the worst. Depending on how (un)lucky you are, there’s more or less aggressive preventive measures to reduce your risk profile. If you have 2 x e2, you’d probably do nothing. If you have 2 x e4, you’d probably aggressively optimize your lipid profile (make sure you keep your lipids (LDL) as low as possible in your body).

– KLOTHO is a gene whose KL-VS variant enhances human cognition. If you have it, lucky you, you may focus on other aspect of your healthspan!

LP(a) gene is associated with artherosclerosis. This gene controls the existence and concentration of a small “add-on” for your lipoproteins, which perturbates the body’s ability to handle blood clots and blood vessels repair and maintenance. The bigger the concentration of LP(a), the higher the risk of ASCVD (atherosclerotic cardiovascular disease).

MTHFR is another gene associated with ASCVD. Depending on what alleles you have, you may be more or less exposed to this disease.

Again, there are many genes that tell you a great deal about your risk profile, and help you take informed decisions about what to focus on when it comes to healthspan optimisations. Some additional resources to read if you want to get into this rabbit hole here and here.

Practical aspects

Once you understand how important this self-discovery step is for your healthspan, you still need to get back with your feet on the ground, and find the right company to sequence your DNA, at the right price, with the right level of reliability. The latter is paramount, because your genome has around 3 billion nucleotide pairs, and a single error in decoding it may mean you taking the wrong measures to optimize your health. For this reason, DNA sequencing is being processed by reading your genome multiple times, and using advanced statistical models to make sure it provides the right data. When it comes to “DNA reads”, the golden standard as of 2023 is 100 times – this is what you would use if you have a suspicion of genetic disease. However, the “reasonable standard” as of 2023 is 30 “DNA reads”, which means that your DNA will be read 30 times to make sure it is reliable.

Following some recommendations, I wanted to try Nebula Genomics but as incredibly as it may sound, they don’t send their kits to France (but they do in virtually any other country).

I ended up working with Dante Labs. I do not have any conflict of interest regarding this company. As of now, I’m still waiting for my results to be analysed and sent back to me. I will keep you informed of the results, as soon as I receive them.

Limitations of DNA sequencing

This “breakneck paced” technological and economic evolution of the DNA sequencing has had surprising scientific consequences: initially, researchers thought that the human DNA was the ultimate book of human life, the “Holy Bible” holding all the secrets of human biology. This is what motivated the consortium of 6 countries (France, Germany, Japan, China, UK, USA) to fund the Human Genome Project, unlocking public money to fund the project.

A few years after the first human DNA was sequenced, the scientific community was to discover soon that this was only half of the story. Indeed, the genome is important – because it stores the information the ribosomes use to produce proteins in our cells) – but what is also just as important (if not even MORE IMPORTANT) is our epigenome: in order to work properly, specific and significant portions of the DNA of each cell are silenced, and do not express themselves. The epigenome describes how our genome is properly silenced, and how and what portions of our DNA is effectively expressed. Well, DNA sequencing tells us what our genome is, but it tells us NOTHING about our epigenome (but other technologies – such as methylation profiling- allow us to do this very cost-efficiently, more in a future blog post).

The takeaway

If sequencing your DNA is of essence, understanding that your life and your future is NOT your DNA is just as important! Your epigenome sits on top of your genome, and much of what is written in your genes – good or bad – can be overwritten by your epigenome, in ways that are still poorly understood today but which are determined by the 5 pillars of our playbook to live 100+ years or more in good health: nutrition, physical exercice, sleep, mental health, medication.

In fact, some studies suggest that your genome influences only 25% of how long you’re going to live, the rest of 75% being your epigenome (read more here).

Update 2023/11/02: for those who want to know more about what I discovered about myself from the results of this DNA sequencing, you can read part 2 here.

Medicine 1.0 vs 2.0 vs 3.0

The evolution of Medicine can be thought of as having 3 major waves in the Human History, and we’re in the middle of a new paradigm shift, a major disruption. This article explains what these 3 major waves are, and how we are quickly shifting from Medicine 2.0 to Medicine 3.0.


When you visit a primary care physician, what is the question he/she’s asking you? I bet that question turns around something like this: “What is the problem / what symptoms do you have / what’s wrong / where does it hurt?”. I would also bet that you may be thinking that this is absolutely normal, and there’s no point in discussing about it, right? Well, not so fast, let’s travel together through the ages, and see how different sets of beliefs have given shape to different waves in Medicine (and what that means for our Healthspan). Peter Attia comes with a very interesting framework to explain all of it, which I would like to share with you in this article.

Medicine 1.0

For a very long time, Humanity lacked any scientific method to study any phenomenon. However, the urge of the Human Brain to find explanations for anything and everything led people to invent all sorts of superstitious or in any case scientifically unproven ways of dealing with the unknown. When it comes to human health, even when doctors tried to apply the scientific method, the complexity of the human body was just too high for them to uncover its mysteries, and they just lacked the technological tools to help them really understand what’s going on.

This is how all sorts of ominous “medical treatments” have appeared through History, and how they persisted through entire centuries or even millennia. Here are 2 of the most popular examples :

– trepanning. Trepanning consists in creating a hole in a patient’s skull. When people had various conditions, such as repetitive headaches, or mental disorders, trepanning was thought to allow evil to get out of someone’s head. No need to say that this was based on superstition and false science, but surprisingly, it worked in some situations, because it indeed decreases the pressure in the skull, which in some specific but rare cases can indeed yield some positive results.


-bloodletting. Bloodletting consists in letting a portion of a patient’s blood to spill out of the body. It was believed to heal many diseases. Similarly as with trepanning, this indeed may be appropriate in some very specific situations, but in the vast majority of cases, it was not only useless, but even very harmful to the patients, by weakening them in the very moment when they needed the most resources from their bodies.


Overall, Medicine 1.0 has been the norm until the 19th Century, and was characterized by chaotic cause to consequence associations, which led to catastrophic measures, often worsening the situation of the patients.

Medicine 2.0

It’s only in the late 19th Century, arguably with the work of Louis Pasteur, that Medicine shifted to a new paradigm. He discovered the Rabies vaccine in 1885, and Medicine changed profoundly after that, thanks to the discovery of vaccines of course, but also and most importantly thanks to the wide use of rigorous science and technological tools to study the human body and its diseases.


Medicine 2.0 tremendously improved public health, and let to incredible discoveries which led to a considerable increase in average lifespan :

– hygiene. Scientists discovered that very small life forms, such as bacteria and viruses, were responsible for a great number of diseases and infections, which could be avoided by simply washing one’s hands.

– vaccines. After the Ravies Vaccine, which turned Pasteur into an all-time international star, many other vaccines were discovered, driving to the almost-elimination of some very common diseases (smallpox, polio, etc …).

– antibiotics. Antibiotics were discovered in 1928 (penicillin), and this pave the way to many other categories of antibiotics being discovered since then. Today, there are more than 100 antibiotics.

Overall, in 2023, we still are in this Medicine 2.0 paradigm, which is characterized by :

-a scientific method which allows to assess, analyse, and treat different conditions. The most sophisticated and strong tool to do this is the “double blind clinical trial”, which proves the efficiency of a treatment beyond any reasonable possible doubt.

-an identified symptom/disease, that affects the patient, and can be easily diagnosed. This is very important, because Medicine 2.0 starts with a well identified problem, that threatens the health of a patient in such a way that it makes it easily identifiable, and places some level of urgency on the treatment to apply.

-a short-term cause-to-consequence relationship between the treatment and any possible positive results, which would put the patient into remission. The notion of “short-term cause-to-consequence relationship” is very important, because it emphasises the advantage but also the limitations of Medicine 2.0. It knows how to deal with relatively impactful diseases, when they can be healed by relatively impactful (and quick) treatments.

A great way to see Medicine 2.0 is to imagine a garage that will indeed repair your car, but with huge limitations as very few of the pieces of your car are replaceable, most of the other parts of your car are used beyond repair, and without doing any maintenance neither (only repair with limitations when something is broken). If you car is already old, the repair will tend to be pretty rudimentary, and will only give your vehicle a short additional lifespan before the next time it gets broken again.

Medicine 3.0

This is where things start to get interesting. Medicine 2.0 was a great way to introduce science into the field of human health. It helped us make a huge leap ahead, allowing us to do marvels when it comes to “quick death” (quick death is a shortcut for those situations where a sudden accident threatens the life of a healthy individual, such as for example a car accident, or an arm being cut and then being put back again by surgeons, or people being stabbed or shot, etc …). However, when it comes to “slow death”, that is chronic diseases (a.k.a. neuro-degenerative diseases, metabolic syndrome, cancer, cardio-vascular diseases), Medicine 2.0 is very limited. This happens because of the following reasons:

– chronic diseases start very early in life, and take decades before showing up. Medicine 2.0 does not know how to study such a long-term evolution.

-because of the differences between humans, and the complexity of the human body, very few treatments work for everyone. Most of the time, some treatment will work for a patient, and not for another one. Medicine 2.0 does not deal well with this personnalisation of the treatments, because the double blind medical trials, mandatory to bring a new drug on the market, are very difficult to apply (if not outward impossible) if we take into account that each patient is significantly different from another one.

Medicine 3.0 is the new wave which is coming as I write this article, to stack on top of Medicine 2.0, and bring a whole new standard of care to the whole world:

-the starting point for Medicine 3.0 is NOT a patient that is sick and needs to heal, but a patient that is in good health and wants to stay so for as long as possible. This is a profoundly different mindset for doctors to have!

-prediction and prevention. Medicine 3.0 understands that each individual’s DNA and lifestyle is a great starting point to predict and ultimately prevent some genetic and epigenetic risk factors. It therefore links causes to far-reaching consequences (for example, having a 2 x e4 alleles of the APOE gene, and not taking aggresive preventive measures to lower one’s lipid profile, increases tenfold the risk of suffering from neuro-degenerative diseases in 40 years from now).

-personnalization. Medicine 3.0 takes advantage of the last technological advances, and allows patients to gather huge amounts of data about their body, their biomarkers and their health in general, which was impossible before (for example, glucose used to be measured only during fasting, at a certain point in time. Only recently do we have CGMs to measure one’s glucose levels in real time). The treatments and preventive measures are also highly personnalised, starting from the premise that a trial and error process is possible before we find the best treatment for a patient. This data is then analized in the patient’s interest, allowing him and his doctors assess how efficient that treatment is. We’re relying less on population averages, and cohort analysis, and more on the specific use case of an identified patient.

Wrap up

Do you believe in this adage, that “a picture is worth 1000 words”? If you don’t, you will certainly change your mind when you’ll see the diagram I’ve designed for you to summarise the essence of Medicine 1.0 vs 2.0 vs 3.0.

Above, you have the average evolution of human health, as years pass by, moving us from birth to the inevitable decline and end of our lives. You can see that there’s a “quality of life threshold”, that is a level of overall health below which life is not worth living for (it may mean for example that you’re living but you’re paralysed, or you can’t take care of yourself, or you have Alzheimer’s and you can’t think straight anymore – overall, below the “quality of life threshold”, life is not worth living for anymore). You can easily see that as we age, our overall health decreases, and eventually reaches the “quality of life threshold”. Our purpose is to act in such a way, that our overall health stays above that “quality of life threshold” as long as possible (for HS100 members, that is at least 100 years old, if not more!).

Well, now that you understand the diagram, let’s study the different lines:

-the red line is the “Medicine 1.0” standard of care: basically people got sick, and when that happened, instead of having positive treatments that would improve their health, they would have trepanning and bloodletting, basically worsening their situations, and accelerating the decline of their health. Not cool.

-the black line is the “No Intervention” at all. That means that when people got sick, basically not doing anything, and letting the human body use its incredible resources to heal itself, was still better than “Medicine 1.0”.

-the blue line is “Medicine 2.0”. This is where we stand right now. Our life gets incrementally better than “no treatment at all”, because even though accidents are somewhat rare in our modern societies (gun wounds, car accidents, etc …), in the eventuality where you suffer such an unfortunate even, you’ll have HUGE chances of survival and remission, when compared to Medicine 1.0 or “no treatment”. However, Medicine 2.0 fails miserably to improve our Healthspan when it comes to chronic diseases. It just isn’t designed to fix these. So what is does instead, is to use infinite amounts of money to keep patients alive for a couple of additional years, but in a very poor general health condition, most often leaving them without any joy of living. This is why you see an inflection of the blue “Medicine 2.0” curve toward the extreme right of it, before intersecting 0, which is the end of life.

-finally, the best curve is obviously the green one, “Medicine 3.0”, where 3P measures (Preventive, Predictive and Personnalised) allow patients to take care of their long term health long before they feel any symptoms of any disease, carefully monitoring decades ahead how their biomarkers evolve over time. This data allows Medicine 3.0 to design efficient measures with long-term positive effects, helping patients stay healthy as long as possible. An interesting side-effect of this approach is that it allows to always focus on the “limiting factor”, ans as such, to increase healthspan, but also generate what is called “compressed morbidity”, which means that the amount of time where people are alive but impaired is much shorter than for the other alternatives.

So my dream is that soon enough, instead of “Medicine 2.0” doctors asking you “what problem do you have” when we start a medical consultation, the doctor will tell you “When I look at your biomarkers, I see you’re in good health, congratulations! Let’s work at keeping it that way for another 40 years!”.

How to think about food intake

Food is one of the 5 pillars of Longevity, and arguably the 2nd in terms of importance (right after physical activity). However, the Media is poisoning us with conflicting information about nutrition. All this massive data is either just noise or bad science, if not outward false information. You only need a couple of minutes to cut through all this BS and understand the fundamentals.


Since I can remember myself, every time when I’ve heard or read of nutrition, it was complex, weakly documented, and chaotic. And therefore lacking any interest. If you want to dive into this and study it for good, it’s indeed terribly complex, and honestly, my conclusion is that we know really little about it. But for most of us who don’t want to become professional nutritionists, things don’t have to be complicated. In fact, they’re dead simple. Read below!


The basics

Food is composed of Macro-nutrients and Micro-nutrients. The Micro-nutrients are nutrients that come in very small quantities, such as Vitamins and Minerals (<0.1% of food). The Macro-nutrients are the categories of nutrients that we find in food in bigger quantities (>0.1%).

The Micro-nutrients

What you need to know about micro-nutrients is :

-they come in many forms and shapes, and there’s no point in listing them all.

-you can find them mostly in vegetables and fruits. Depending on your specificity, you may need to take supplements to compensate for lack of different vitamins (for example B complex, or Mg, etc …).

The Macro-nutrients

There are 5 categories of Macro-nutrients:

-fats. Fats are very energy-dense. During intense or prolonged efforts, fats can break down and generate energy for the body. Fats are divided into 3 categories, saturated, mono-unsaturated and poly-unsaturated, but more about this in a future blog post, no need to over-complexify at this stage.

-carbohydrates. Sugar and starch are carbohydrates. Depending on how good your body is to process these, you may be better off avoiding carbohydrates as much as possible. Carbohydrates are quickly digested and released into your blood in the form of glucose. This mechanism, repeated over and over again during decades, may end up destroying your energy sensing mechanisms, and ultimately creating insulin resistance and type 2 diabetes. This is what we’re trying to avoid as much as possible with a CGM.

-proteins. Proteins are very important, because they’re the building blocks of your muscles (among others).

-fiber. Fiber is not a nutrient per se, because the body does not process it, but it’s very useful to the digestive system and is present in large quantities in the foods we eat.

-alcohol. It may come as surprising, but alcohol is a macro-nutrient. It is almost as energy-dense as the carbohydrates. It may be a social enhancer, but remember that while your body can cope with reasonable quantities of alcohol, unlike what you’ll see in articles here and there, it does NOT improve your health. So don’t believe what different lobbies tell you, don’t lie to yourself.

Your goal

So now that you know that food is Micro-nutrients (vitamins) and Macro-nutrients (fats, fiber, carbohydrates and protein), the next step is to understand what you’re aiming for when it comes to daily food intake:

– a daily overall energy intake of roughly 2000-2500 kcal (kilocalories) for men, and 1500-2000 kcal for women. Each macro-nutrient (except fiber) has a caloric value.

– a daily protein intake of 2g / kg (that means if you’re 70kg like me, you’d need 140g or protein / day). This is above the recommended “official” doses of 0.5 – 1g/kg, but recent studies show that this standard daily dose is absolutely insufficient.

– depending on how your body reacts to carbohydrates, you want to limit these, because as explained earlier they turn into glucose in your blood and you want your glucose levels to stay ideally at an average level below 100 ml/dl, with no spikes above 140 mg/dl and a GV (glucose variability) of less than 15%. You can measure this by wearing a CGM. There’s no general guideline as to how many carbohydrates to eat, you’ll just need to adjust it depending on your own body.

– very interestingly, most processed foods are unhealthy even when they contain the right macro-nutrients in the right proportion, so your aim is to eat as many unprocessed foods as possible. Eat vegetables you cook yourself, eat a fruit and not an fruit juice, etc. Not all the processed foods are bad (for example the Whey Protein), but most of the time, it’s easier to avoid them.

Putting this into practice

I’ve been putting all these guidelines in practice for the last couple of weeks, and I must admin it’s awkward and strenuous, but worth it to my eyes.

So it all starts with carefully reading the notice on every food package, where you’ll have the macro-nutrients quantities for each product, an example below :


The plan is to add all the macro-nutrients of the different foods you eat, do the math for a couple of days at least, and make sure that numbers add up to roughly the desired quantities (in terms of calories and protein intake, see above).

If you do this right, you end up with something similar to this:


In my situation, you can see that I’m roughly at 2000 kcal / day, which is ok, and around 120g of proteins / day, which is slightly sub-optimal (I should be at 140g). The quantity of carbohydrates is roughly between 50 and 100g / day, which is the maximum amount that my body can bear without releasing glucose in excess in my blood. Remember for you it may be more (lucky you!) or less.

On the longer term, once you get an intuition of what to eat and how much, you can discard this process of measuring everything, but first you need to get a sense of how this is working.

Indeed, later on, you’ll be able to monitor your food intake in a much more comfortable way, that is through measuring how much you weight on a monthly basis, and how much fat and lean mass you have with a DEXA scan every 3 months or more (but more on this in a future blog post).

A couple of practical observations

You’ll see that eating 2g of protein / kg / day is very hard (especially when you limit the overall energy). This is why I take some form of concentrated protein shake, called “whey isolate”.

I was also terribly surprised to notice that eating healthy in restaurants (even the more sophisticated French restaurants) is close to impossible. Indeed everything is filled with sugar and starch (sauces, soups, french fries, fruit juices, even gazpachos!). I’m not saying that it is absolutely impossible, and I’m sure in Paris for example, there may very well be some niche restaurants where you can eat a longevity-friendly meal, but it’s not mainstream, it’s not practical, it’s not the snack in the corner of your street, you need to be a connoisseur.

Another interesting observation is how marketing is distorting the message on healthy foods. In almost every restaurant you’ll have some “veggie” meal, and most diet-sensitive people will openly prefer that and think it’s healthy. It’s false, vegetarian food does not necessary mean healthy food (sugar and starch is vegetarian), and meat does not necessary mean unhealthy food (poultry and fish are great for health).

Wrap up

In a nutshell, here’s what you need to remember:
– you need 2000-2500 kcal / day for men, and 1500-2000 kcal / day for women
– you need roughly 150g of protein if you’re a man, 100g if you’re a woman
– you need to keep carbohydrates and processed foods as low as possible
– eating various vegetables and fruits will give you the necessary micro-nutrients

That’s all! Isn’t that easy?

PS1. Please note that my goal is to share with you what I discover, I’m not a doctor nor a nutritionist, and most likely, the article contains some approximations which would sound dissonant to an expert. However, I want to help as many people as possible understand the most fundamental mechanisms of nutrition, and provide them with insights that are easy to understand and apply today.

PS2. I hear some of you think outloud “Where’s the pleasure of eating delicious foods? French specialties? Exotic tastes?”. While I totally respect this point of view, the food industry has evolved in the last century to optimize for price, volume, regularity in production, and palatability, not long-term health. While a mix between both may be possible (healthy + tasteful), you really need to understand the rules of the game, and adjust accordingly.

Time is Money

Longevity and Money Management are 2 sides of the same coin. Once you understand that, you can easily apply all the lessons you’ve learned so hard during your life about finance and business in your Longevity Journey.



The Law of Compound Interest

Einstein has famously stated that “the people who understand compound interest will earn it, and those who don’t will pay it”. The general idea is that a small amount of money invested today, which generates a small interest every year that passes by, will eventually grow very big with small effort, if we keep the money invested long enough.

Well, when it comes to Longevity, it’s the same: the earlier you start, the greater the benefit, and the small effort you put today will eventually compound itself over the years and reward you with huge returns. Recent studies tend to prove for example that plaque in your arteries starts to accumulate as soon as in your teenage years, and this process continues under the radar for decades, until you get older and your arteries eventually get clogged. Preventing this from happening when you’re young takes a small amount of effort, but pays big decades after you’ve made this investment in your health.

There’s no “one size fits all” solution, no magic bullet

If I’d ask you how to get rich, and ask you to guarantee the success of that method you’ll come up with, you’d find this ridiculous, you’d probably laugh, and you’d certainly be right to do so! Succeeding in investment or business depends on your psychological profile, your education, your knowledge, how early you start, your risk aversion, your patience, and the other so many parameters that make you YOU. The world we live in is complex, and at least partially unpredictable. You have to make your bets, take risks, and find the right balance between persistence and flexibility.

Well, it’s the same for your Longevity Journey. The human body is just as complex as our economy, partially chaotic, and impossible to predict. In addition, it’s different for each one of us. So far, science has uncovered only a small fraction of how our biology works. So the solution in such a situation is to deal with uncertainty, follow a process of trial and error, until we get things right, accumulate knowledge about ourselves, and complete it with new discovers as they come along. Just as in business, there’s no easy way towards success, it’s going to take time, failures, there’s no magic recipe. But just as in business, work and consistency will eventually usually pay off.

Advice is cheap

I may sound controversial, but do you leave your wealth, you hard earned money, in the hands of so called “experts”, blindly trusting them to act “in your interest”? I’m not saying that you don’t have to listen to other’s opinions, be stubborn and take decisions in a vacuum. I’m saying that the healthy attitude when it comes to your money, is to listen carefully to everything everyone has to say, do your best to understand their point of view, and then do your homework by analysing everything, and then taking what seems to be the best decision for you. Financial advisors may have or have not conflicts of interest, but even if they don’t, they’ll never be as concerned as you by your own success.

Well, investigating and trying to understand as much as possible when it comes to your Longevity Journey is the right attitude to have also. Doctors have most of the time pure intentions, but :
– many times, they’re don’t agree with each other, which means that there’s no absolute truth, so that’s fine for anyone to have opinions, but you’re the one to make the final call
– they may have conflicts of interest, with Big Pharma educating them to prescribe certains treatments
– they don’t know you well as you know yourself
– they won’t be the ones suffering the consequences of the decisions they take for you

I don’t want to criticize doctors, I think they do the best they can given the complexity of their mission and the resources (time, money, knowledge) they have to do their job. However, just as you’re ultimately in charge of controlling your Money, you’re also ultimately in charge of controlling your Health. And there’s no one better suited than yourself to take the hard decisions for yourself.

Save for retirement

Most of us have a long-term financial plan. If we’re employees, our “Friend the State” may take care of this, through mandatory pension contributions on our wage. If we’re business owners, most of us have some sort of saving / investing plan for the long term (for example in the form of real estate, a low ROI / low risk investment). I can hardly imagine any responsible serious adult not thinking about their financial wellbeing in the very long term in one way or another.

Well, if you manage your financial capital for retirement, there’s no point in not managing your health capital for that time of your life also. The situation you want to find yourself in at that stage in your life is to be financially wealthy and at the same time physically and mentally healthy. And who knows, with a little bit of luck, you’ll have an interesting job and maybe you won’t have to retire anyway!

The 4 Angels of Death and How to Escape Them

Our Healthspan is limited by 4 Major Age-Related Diseases. In this article we learn what these 4 diseases are, and how we’re escaping from them.


Medicine may seem complex (and it really is, when explored in detail), but this doesn’t mean we can’t get a plane view of what’s going on, and how to use this knowledge to our advantage. Indeed, the ICD (International Classification of Diseases), the world reference to date, created and published by the WHO (World Health Organisation), lists more that 55 000 diseases. However, make no mistake, this complexity is unnecessary to most of us, we need to focus on the fundamentals: if you want to optimise for healthspan (that is, the number of years you’ll live in good mental and physical health), and unless you have some specific/rare/particular condition, you need to pay attention to only 4 chronic diseases, which I have called “The 4 Angels of Death”.

Now, the fascinating part is that these 4 Angels of Death play a different game with each one of us. That is, they start in different positions, and come for us at different speeds. It’s like a huge life-long Pacman game. And if we’re good enough, just like in Pacman, we can escape from our ennemies, and get to the next level … So our job is first to study them in general, and then allocate our efforts and resources escape from them efficiently. Indeed, out of the 4 Angels of Death, our strategy is to always focus on and avoid the one who is closest to us, and moving the faster in our direction. There’s no point in spending too much energy on the ones who are far away, we need to fight the one who is actively threatening us the most.

So let’s start by listing our 4 ennemies. For each one of them, I’m giving some preventive measures which allow us to avoid these diseases. This is very complex, so I’m barely scratching the surface of this, and by the way I’m not a doctor, but the only reason I’m doing this is to send a message of self-responsibility and hope. We’re not powerless in the face of these diseases, we have tools to fight back and escape them.

Metabolic Disorder

In a nutshell, Metabolic Disorder is a cluster of diseases which have all in common the fact that your body can’t properly manage energy anymore. That means it can’t store it properly, can’t process it properly, or use it properly. Most of the time, it’s diabetes type 2 (your body can’t control the glucose levels in your blood), but also other conditions such as hyperinsulinemia (too much insulin in your blood), fatty liver disease, insulin resistance, etc.

I’m starting with this disease, because most of the time, people don’t die from it, but it is in some sort a very favourable “bedrock” for all the other chronic diseases. So avoiding it is a great strategic move.

Some examples of how to avoid this category of diseases:

– optimise your glucose levels

– optimise your BMI (Body Mass Index)

– physical activity (but not any activity, more in a future blog post)

Cardiovascular and Artherosclerotic Diseases

This is the number 1 cause of death. Everyone has had a friend, or a family member, who died of heart attack, or stroke. This is not coming from anywhere, each one of us may have a hereditary predisposition, but this is totally avoidable with the right preventive measures (more of it in a future blog post).

This category of diseases starts attacking our arteries decades before any symptom appear. Some examples on how to avoid cardiovascular diseases :

– sequencing our DNA to find out if we have a mutation which significantly increases our risks, called LP(a). If we have it, we have to aggressively reduce our LDL (Low Density Lipo-Protein, common called Bad Cholesterol).

-monitoring the general health of our arteries (for example using a Computer Coronary Tomography Angiography – CCTA).

– regular lab tests to monitor our LDL, HDL, ApoB, triglycerides (a bit technical, will come back in a future blog post). These results have to be be interpreted by a doctor, but you don’t have to wait to feel sick to do them.

– adapting one’s diet depending on the results of the 2 aspects aforementioned.

Cancer

If Cardiovascular Diseases is the number 1 cause, then Cancer is definitely number 2. Everyone knows what cancer is, no need to further explain it, however I think it’s important to mention some less-known facts about this disease:

– it’s not a disease, but a cluster of many diseases, each cancer is different, and this is also one of the reasons why it’s so difficult to treat it

– we all have cancers all the time, which is not a problem most of the time, it’s just that our immune system is so efficient at addressing cancer cells we are not even aware of them

– despite huge amounts of money and R&D effort poured into cancer, we still haven’t found strong treatments to fight it, especially when it is metastasized (which means that the cancer cells are not in one place anymore, but have moved basically everywhere else in your body).

There are some very interesting treatment for cancer (most of them still in clinical trials), most of them related to monoclonal antibodies and/or gene therapies, but for now, the best strategy we have at hand is to:

– keep our immune system as healthy as possible

– screen for cancer on a regular basis, through MRI and a new disruptive test called GRAIL, which detects more than 50 cancers from a simple blood sample

Neuro-degenerative diseases

This category of diseases encompasses Dementia and Alzheimer. It’s not the death of our bodies, but of our minds. There is a lot of mystery around this disease, and we don’t really understand it well. It seems to be caused (or at least associated with) high levels of 2 proteins in our brains, called “amyloid beta” and “tau”.

Different mechanisms are explored for neuro-degenerative diseases, but what is important to know for our purpose of maximising healthspan is that:

– there’s a mutation called APOE, which multiplies by around 10 the likelihood to suffer from neuro-degenerative diseases. A simple DNA sequencing test can identify that.

-possible routes towards neuro-degenerative diseases are: either through metabolic disorder (because your neurons don’t process glucose as they should), either arthero-sclerotic (because your neurons are not properly provided with the necessary nutriens, which cannot properly travel through your clogged arteries), either cognitive (in short, improper brain stimulation/no purposeful in life/insufficient social interaction).

What you can do to prevent neuro-degenerative diseases:

– fulfil your life with meaningful social interactions.

– stimulate your brain through intellectually challenging activites.

– optimise your physical health against artherosclerosis and metabolic disorder.


This article may seem depressing, but on the one hand, understanding the rules of the game we’re playing will allow us to resist longer, and an amount of 20 or 30 additional years of healthy life is an absolute win in itself. On the other hand, by extending our healthspan, and staying alive as long as possible, we increase the probability of getting cured from these diseases thanks to new discoveries and breakthroughs coming in the next decades. We have a plan here!

What’s a CGM and why you need it

If you want to reach a Healthspan of 100+ years, you definitely need to play with a Continuous Glucose Monitor (CGM) at least a couple of times in your life. Read below to understand what it is and why it is so important. I’m not a doctor (and I assume you’re not either), so I’m over-simplifying the complexity of the human body to explain everything.


The CGM

A CGM looks like a small white coin (see below on my arm).

The one I’ve chosen is called Frestyle Libre 3 from Abott Technologies (I have absolutely no stake, no hidden interest whatsoever in this company), it costs roughly $75. It lasts exactly 14 days from the moment you install it on your arm until it expires and you have to take it out and throw it. Its job is to measure the concentration of glucose in your blood every minute.

The role of Glucose in your Body

In a nutshell, Glucose is the fuel of your cells. When you eat, your digestive system breaks down food into different components, and glucose is sent into your bloodstream. If there’s too little of it, your cells don’t have enough energy. When there’s too much of it, serious and dramatic consequences may occur (such as loss of vision, kidney damage, etc …). So your body has an efficient lever to maintain your glucose level under control, a hormone produced by your pancreas, called insulin. Insulin may be considered as “the hormone of abundance”, because when you’re eating more than your body needs (abundance), the production of insulin will tell your body to store that additional glucose in your cells (mostly fat cells, liver and muscle cells).

So what?

You eat sugar, it flows into your bloodstream, then insulin tells your cells to absorb it, end of the story, so far so good right? Well, not quite, and this is where things get tricky and interesting!

During your first decades of life, this glucose / insulin system works perfectly, fine-tuning your glucose levels 24/24 and 7/7 to keep you healthy. However, as you grow older, your cells may become resistant to insulin, so that your pancreas needs to produce more and more insulin to keep your glucose levels within the desired limits, which is called “insulin resistance”. Most of the time, this happens because of decades of excessive quantities of sugar you ingest, associated with glucose spikes in your blood, which generates insulin spikes to compensate. Eventually, this vicious circle of your pancreas producing more and more insulin, and your cells becoming more and more resistant to insulin, ends up into diabetes (or more generally metabolic disorder), which means your body just can’t control glucose in your blood anymore.

If you want to live long and healthy, you want to avoid this at all costs. Metabolic disorder is the “foundation” of all the chronic diseases, which means that people suffering from this will have a skyrocketing probability of suffering from every other age-related major chronic disease (neuro-degenerative, cancer & cardio-vascular).

From Theory to Practice: Flatten the curve!

Now that you know how important it is to keep your glucose levels within a normal range, let’s get from theory to practice! So ideally, you want a fasting glucose level between 60 and 99 mg/dl (in the morning when you wake up, before having breakfast), and during the day, a glucose level as flat as possible. When you eat, depending on your diet, the glucose level will rise, then insulin will bring it back down, but you want small rather than ample variation around the mean.

Each individual will react differently to different foods, so this is why a CGM is essential, you can’t rely on how an average person reacts to a specific food. You need your own user’s manual!

So you have 14 days with a CGM on the back of your arm, this is the one time in your life you can eat the most delicious but unreasonably unhealthy food, just to see how your glucose levels spike (or not). Try everything, junk food, sugar, cake, soda, you name it. Let’s roll baby!

My personal use case

I’ve been wearing my firs CGM for 4 days now, and I’ve tried around 30 different foods, and here’s some examples of what I’ve learned about myself:

– fast-food skyrockets my glucose levels, I mean really crazy, above 230 mg/dl (which is huge), I’ve tested a Quick Giant + a big Coca-Cola + nuggets + lots of ketchup and mayonnaise. Yummy, so delicious, what a pitty!

– those delicious Liegeois with whipped cram send my glucose level to the sky also

– curiously, Taboulet Oriental (Tabbouleh) and Corn also triggered a spike, even more so than a that delicous but super-sugary chocolate “Toblerone”

– orange jus, fruits, potatoes, and pasta seem to be well tolerated, generating no spike of glucose

– 1h of moderate effort like jogging does not seem to influence my glucose

I’ll still test: different types of alcohol, and also sleep deprivation to see how it affects my body’s ability to control blood glucose. It seems from some studies that on average, sleep deprivation reduces your body’s ability to control glucose by as much as 40%. I can’t wait to test this!

Watch out for prediabetes

In addition to helping you understand what food to avoid, a CGM may also teach you something even more important, which is what your diabetes profile is. Oh boy could you have a big surprise (read below)! Diabetes is when your body can’t deal with glucose, because the insulin is either not produced in enough quantity, either because your cells don’t respond to it anymore :

– a glucose level of <100 mg/dl is OK

– a glucose level of 100 – 125 mg/dl means you may be prediabetic.

– a glucose level >125 mg/dl means you have diabetes

Knowing a couple of things related to prediabetes are of essence for your healthspan:

– prediabetes is most of the time asymptomatic, you don’t know it, you don’t feel it – until it is too late!

– prediabetics have an order of magnitude of 5 years of delay between their prediabetic condition and “type 2” diabetes. This is 5 years they won’t event be aware of, because as explained below, this is asymptomatic.

– this condition is extremely common, 80 million americans have it (out of 330 million roughly), which is almost 25%!

Prediabetes: if I may have it, you may have it!

Now, I’ve kept the most interesting part for the end of this article: during my first 4 days of CGM usage, my device has consistently measured a glucose level above 100 mg/dl, with variations between 100 and 200 mg/dl, and most of the values being around 110 mg/dl. If you’re carefully read what I’ve written above, you should understand that this means that I may be prediabetic.

I thought of myself as being almost perfectly healthy, and I invest a great deal of time and effort into staying into shape: I don’t drink, don’t smoke, I’m not overweight, I eat healthy (or so I think), I sleep well, I’m not stressed, I practice sports 5 times / week, etc …

It’s true that I have one diabetes “type 2” case in my family, but I thought it was because of a lack of care.

I have to do additional exams, before I consider this as a certainty, but my takeaway here for you is double:

1. if I have prediabetes, you may have it, don’t sleep on it before it is too late. Remember that 1 in 4 people have it.

2. detected and acted upon early, prediabetes is reversible. Don’t waste your time, don’t act like like an ostrich hiding its head in the sand, and hoping for the best.

Because I do care so much about your short and long term health, I want to ask 2 questions: Are you going to look elsewhere and hope for the best when it comes to your diabetes profile? Or are you going to start finding out as much as possible about your body by ordering a CGM today?

Practical Steps to Improve your Healthspan

Some readers (thanks Gene!) told me the recent discoveries in medecine were fascinating, but most of all, they were interested in having actionable insights into what they could do TODAY to improve their Healthspan. I’m giving a couple of prioritized measures to take. Let’s dive into it!


The Youth Pill

I will maybe dissapoint you, but just as there is no silver bullet to get rich, there is no magic pill to keep you young and healthy today (by the way, I’ll write a dedicated post about how similar longevity and money management are, stay tuned!). What we do have, however, is the ability to explore one’s health and body, and come up with a personalised, risk adjusted, long term plan to follow in order to reach 100+ healthy years. Depending on how quickly science moves forward, new breakthroughs are expected to help us improve even more our strategy and tactics, and eventually increase our odds to leave even longer and healthier lives (there’s a very interesting concept related to this, called Longevity Escape Velocity, which I’ll explain in the very following weeks).

First step: find a Medical Doctor specialized in Longevity Medecine

Every time when I think of Longevity, I first think of Money Management and try to evaluate how I would react in a similar situation. How to start in Longevity? Well, how did I start Investing in first place? A year and a half ago, I was a total ignorant in Money Management. One of the very first things I’ve done, was to get some professional help (from Finance Advisors and Investment Banks). I have considered none of what these Experts say as “Guaranteed 100% Verified Knowledge”, but I have questioned each one of their assumptions, statements and theories, and built mine on top (and most times against) those constructs. What resulted from this exploration process was a personal set of principles, convictions and an encompassing strategy which consistently guides my steps when it comes to Investing, that are sometimes similar but sometimes opposite to the so called “expert advice”.

Similarly, when it comes to Longevity, if there was only one thing you had to do to start your Longevity Journey, that one single step is, without any doubt, to find a Longevity Expert to assist you! The Human Body is a marvel of complexity, and what you’ll want to avoid at all costs is to hurt yourself by taking decisions based on an over-simplified version of what’s happening with you and how your body works. A Medical Doctor will assist you, help you take informed decisions.

Just so that you understand what to expect from such an Expert, this is how he will be able to help you:

– help you list the lab exams (blood, urine, etc.) you need to do, the ideal frequency for you, and interpret them. For example, if you have a cancer family history, you’ll want to do some detection tests more frequently. Same for Calcium Plaque for Artherosclerosis. This is highly technical, and unless you’re a health professional yourself, you’ll need guidance on it.

– help you find a Long term Longevity Strategy for you to execute. This amounts to finding the weak points in your health (current or to come), and build long term strategies to downplay them. For example, if you have a certain predisposition for Diabetes called LP(a), you’ll probably want to keep your LDL as low as possible (way below the commonly admitted threshold agreed upon in “standard medecine”).

– help you with tactics to improve (or maintain) your health, which means practical stuff to apply today. This may consist in a plethora of measures, just to give you a couple of examples: specific diet changes, physical activity, drugs, etc … This is where it gets tricky, because you’ll probably have the option to take some drugs that are commonly used for specific conditions, so they’ll improve some aspects of your health, while deteriorating some others, which may still be a good deal for you. The deeper you’ll go into it, the more this will be subject to a trial and error process, and risk adjustment.

– help you in real time with the dynamics of the whole process, how to adjust your strategy to the new scientific breakthroughs, the new problems that may arise in your health, what additional tests to do (or what to stop doing), etc. You are a living human being, you evolve, just as does the scientific knowledge associated with your body. Setting it up once and for all is great, but it’s not enough, you need to keep yourself updated!

As you see, the key word for the Assistance you’ll get from a Longevity Doctor is “help”, he will assist you, guide your journey, but you’ll have to make the final choices for yourself. You’re the CEO of your own health, nobody decides for you when it comes for such important decisions.

Important caveats here:

– just as there’s no absolute investment strategy, as each one of us evaluates and reacts to risk in different ways, there is no absolute Longevity action plan for you to execute blindly. No doctor will ever give you that (in fact anyone can tell you what to do, but that will be most likely sub-optimal). You have to find your own balance between short terms vs long terms risk, efforts and rewards. Just like in Investment, there are some no-brainers to apply with maximum confidence, but once you’ve executed that, you’ll never be able to sleep on your 2 years, you’ll never be 100% sure that you’ve taken the absolute right decisions. But you’ll improve systematically towards that goal!

– as of 2023, you’ll have a hard time finding Medical Doctors who understand what Longevity is and how to help you with it. This field is brand new, reaching some basic level of awareness in some countries and less in others. Things aren’t easy. When you’ll find such a Doctor, they may be overly expensive (I mean $30k / week), or pain incompetent. This is definitely harder that just visiting a doctor for a sore throat consultation. I’m taking about this in one of my previous posts. It’s going to be tough, but it’s definitely worth it! I’m openly sharing who’s my doctor and others I was able to find, with whoever wants to know more. Just write me and I’ll help you with that.

Next steps: some examples

I’d say that being assisted by a Longevity Medical Doctor is more or less the only aspect that should be common to everyone, and you should do prior to any concrete initiative to Improve your Long Term Healthspan. Once you have that in place, congratulations, you may be interested in taking other more tactical measures according to your preferences, lifestyle, and goals, such as:

– use some wearables. For example, I use an Oura Ring, which tracks a bunch of biomarkers, such as HRV (Heart Rate Variability), temperature, sleep quantity and quality, general physical shape, etc…

For me, the Oura Ring was a game changer, because before wearing it, I was overtraining and putting more pressure on myself that I was able to bear. This resulted in poor physical performance, a weakened immune system, chronic stress. All of these were blind spots before I was able to understand them thanks to my Oura Ring. The balance between effort and relaxation is a very important factor when it come to long term health.

– read as much as possible on longevity and functional medecine. Just as you sometimes have difficult Investment Decisions to take, and no one is more suitable than yourself to take them for you, there will be similarly difficult Health Decisions you’ll need to take. In order to be best prepared for such situations to come, you’ll have to read as much documentation as possible, on how the body works, and focus on your specific weaknesses. There are books, films, clinical studies, experts, new technologies coming down the road, in those fields. Find out as much as possible about them. Depending on how serious some condition is in your case, you may be tempted to test more or less experimental treatments (depending on the laws in your country of course).

– other tactics include CGM (Continuous Glucose Monitors), Epigenetic Clocks, Glycan Age Clocks, various invasive and non invasive tests, HBOT, Red Light Therapies, etc … but I’ll elaborate on those in detail in my next blog posts.

Overall, at first sight, it may seem a bit conceptual, daunting and blurry, but again, just as with Investing, after some time and effort to understand how it works, you’ll end up creating your own style, strategy and tactics with your own appropriate amount of regular adjustments and allocated time to it. It will most likely come down to specific measures to take in terms of food intake, physical activity, sleep/rest, lifestyle, and maybe (this is the trickiest) preventive supplements or drugs you’ll maybe take.

The Yamanaka Factors

It looks like science-fiction, but it’s actually fact-based science. Shinya Yamanaka got the Nobel prize in 2012 by turning differentiated cells (also called somatic cells) back into stem cells. This opened a whole new R&D universe to explore, whose practical applications should be starting to appear in the very next years.


Crash course in Cellular Biology

For accessibility purposes, I’ll make some approximations here, because I want the content to be easy to understand, so that everyone gets how disruptive this major scientific breakthrough is. Please don’t kill me if you’re an expert in microbiology 🙂

Stem cells are undifferentiated cells (similar to the ones that grow once a sperm and an ovocyte met). As the foetus grows, the inner structure grows more an more complex, and mechanisms we do not fully understand today contribute to the specialization of stem cells into neurons, muscle, skin, etc… During our lifetime, stem cells continue to exist though, disseminated everywhere in our bodies, ready to take over in case of accidental or systemic cell damage. When this happens, stem cells follow a complex process of migration and differentiation, which ultimately allows them to replace the damaged tissue.

Once a stem cell specializes into a somatic cell, that cell will fulfil its function, live and probably die at some point. It’s a one way ticket decided by Mother Nature for that cell, which will normally never return into a stem cell again.

The DNA of a stem cell differs from the one of a somatic cell by what called the methylation of the DNA, which is a mechanism by which some portions of the DNA become “blocked” or unreadable and only the portions of DNA which are relevant to that specific category of cells will be expressed again. It makes total sense, as you want a neuron to behave like a neuron, and not like a skin cell, or the other way around, etc.

This is a very simplified version of how Mother Nature works.

The Yamanaka Factors

Yamanaka discovered that there are 4 genes, called the Yamanaka Factors (Oct3/4, Sox2, Klf4, c-Myc), which, when over-expressed to different degrees and combinations, result in any differentiated “adult” cell turning back into a stem cell. That stem cell can then be multiplied at will, and then be differentiated again into any other kind of somatic cell. In plain words, this means taking for example a skin cell, turning it back into a stem cell, and then turning it into a neuron – for example. Mind blowing!

Ongoing Research Projects related to the Yamanaka Factors

There are numerous ongoing projects, I’ll just give a couple of examples, just to barely scratch the surface of such an extensive and fascinating field of research:

– stem cells based therapies. The idea is either to inject stem cells in damaged issue, so that it regenerates faster and better. Another idea is to extract somatic cells, turn them into stem cells, then turn them into specialized cells, and then again provide them locally where they’re most needed. Although not yet approved in US & EU, meet 40 world-class athletes who are using or have used stem cells therapies (Rafael Nadal, Cristiano Ronaldo, etc.)

– create and grow organs in a flask, and then transplant them into human bodies. The process begins with your own cells, which are then differentiated into specialized cells, then multiplied, through a complex process as you can imagine, and then ultimately grown into full sized functional working organs. All of this would have never been possible without using the Yamanaka Factors. For example, meet your future heart if at some point you’ll need a new one.

– last but not least, it seems possible to apply a partial “mild” activation of some of the 4 Yamanaka factors, so instead of totally reverting a somatic cell from its current state all the way back to a stem cell, that cell is just partially rejuvenated. It keeps its specialization, it does not become a stem cell, but instead of being old and damaged, it is just gets youthful again. This is called “epigenetic reprogramming” and is currently the most promising field in aging research. Altos Labs (arguably the best founded longevity company today, sponsored by Jeff Bezos amongst others) is working specifically on this cellular reprogramming technology, and they’re betting big on it.

Caveats and current limitations

The main problem today, when it comes to reverting somatic cells to stem cells, is that during this process, some of the resulting stem cells become cancer cells, quickly multiplying and creating tumors.

One other problem is that while scientists know how to take a single cell and manipulate it “in-vitro” with regard to these Yamanaka Factors, doing the same thing with multiple cells, and making sure that each and everyone of them corresponds to the expected differentiation stage, is a challenge. Doing so “in-vivo” is even more of a challenge.

However, when it comes to practical applications to come, there are so many companies, and so much money has been invested into this technology, that it is one of the most (if not THE most) promising research domains today, the hottest topic in the field.

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!

Numbers and Facts about How Food is Impacting your Lifespan

Main takeaway: statistically speaking, healthy food can get you more than 12 years of additional lifespan (and probably much more in terms of healthspan).


Today I’d like to talk about food, but not in the way you read about it all day in glossy magazines or TV shows. We know we need to eat healthy. We roughly know what this means. But then, all this is usually presented in a very impractical and clumsy format: a very explicit (and hard to follow) rule of how and what to eat, and then, a very blurry, long term, shady benefit, to “improve one’s life when you’ll be older”. In other words, do a sacrifice NOW, and for a hopeful long term, weakly defined, benefit.

I knew how hard it was to restrain myself from unhealthy (but so tasteful) food, so in order to motivate myself to follow these recommendations, I also needed to evaluate and quantify the future benefit of this effort. By chance, a friend told me about an interesting app to ponder the “effort to benefit” ratio (thank you JB 🙂 ). Under a unsexy and very basic design, this small app is exactly what I needed: you type in some data about yourself and what food you eat right now, and it computes how many additional years of life you get if you start eating healthy food, statistically speaking.

Before I let you know the app, so that you can play with it yourself, a couple of takeaways to remember:

– the difference between eating “average food” and “optimized for longevity food”, is a whooping 12.2 years of lifespan (statistically speaking). If we speak about healthspan (that is years of healthy life, without major diseases), the difference may be even bigger (more about this in future my future posts). Eat junk or “average food” and live 77.8 years (probably in a pitiful shape in the last 10 – 15 years of your life). Eat healthy food and live 90 years old (probably with what is called a compressed morbidity in the last couple of years of your life – which means you’ll be ill a short amount of time before you pass away). Now THAT is a quantified equation I can use to motivate myself to eat healthy in the present.

– the food to eat as much as possible is, with no big surprise: vegetables and fruits

– the food to eat in a moderate quantity is: whole grains, fish and milk

– the food to avoid at all costs (bring it to 0 is possible) are processed meat, red meat and sugar

– one very interesting way to see it (and think of it, when you ponder whether to eat or not a specific product), is to see how many years you’re gaining (or losing) when playing with one or 2 parameters at once: for example, if you don’t eat your vegetables you lose 2 years of lifespan, if you don’t eat vegetables and fruits altogether, and lose 3.8 years of lifespan. And then, taking the right decisions on each category of foods, one by one, adds up considerable years to your lifespan.

The app I’ve used to help me understand how impactful healthy food is for longevity is https://priorityapp.shinyapps.io/Food/. I hope you’ll like it and by playing with it, it will help you decide what makes sense for you in terms of healthy vs tasteful food, between the short term pleasure (eat a tasteful meal), and the long term benefit (live longer healthier).