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 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).