🔎Betting on the superrich supercentenarian.
In the future, mortality will not be the great equalizer anymore. Instead, it will accelerate inequality and add an entirely new dimension to it.
TLDR Summary
In a world with obscene inequality (that seems to be getting more obscene every day), there is one comforting thought: No matter how much richer some people are on paper compared to you, their clocks tick as fast as yours. If you live a reasonable life, Jeff Bezos’ billions don’t raise his odds to outlive you by much.
I believe this will change drastically in the coming decades. We will see rich people making it far into their 100s en masse and average people likely won’t. Our mortality will not be the great equalizer anymore. Instead, it will accelerate inequality and add an entirely new dimension to it.
Medical R&D typically targets very specific diseases. But if you look at all these efforts in combination, they form a large mosaic that tells the same story. All healthcare R&D ultimately follows one overarching objective: Delay death.
Our mission to delay death is becoming increasingly expensive. We have harvested most low hanging fruits such as proper nutrition and hygiene standards. Additional gains must come from professional longevity management and from breakthroughs in medical R&D, via clinical trials that cost billions of dollars.
Those breakthroughs are happening right now. But it will be difficult to offer them to the population at large. Healthcare providers must generate returns to justify their spending. It will be increasingly difficult for most people to afford state-of-the-art healthcare. Many public social security systems are at their breaking points. Some are already beyond. And AI is disrupting the labor market which causes uncertainty about how much bargaining power legions of white collar workers will have in the future.
Therefore, medical R&D will primarily be funded by the wealthy who will then also be the ones enjoying its results. Individualized, professional & high quality healthcare and lifestyle management will become the ultimate luxury good. If you are looking to serve the most potent consumer of the future, think about the superrich supercentenarian.
From mortality as the great equalizer…
In Time is a 2011 movie starring Justin Timberlake that made a lasting impression on me. In this movie, people were genetically modified to stop ageing on their 25th birthday. As a means of population control, they were also equipped with a biological timer that killed them once it hit zero. Additional time could be acquired through labor or through transactions with others. Time literally became people’s currency. In that movie, Timberlake’s character was initially poor and fighting for survival. He then got the opportunity to become rich and challenge the system.
Unfortunately, the movie degenerated into an uninspired Bonnie and Clyde flick in its second half. But its premise was both fascinating and terrifying. We often say ‘time is money’. This movie explored what that could mean when taken literally.
I don’t know about you. But I find it pretty comforting to know that most of us are equal in birth. As long as we are not born in extreme poverty and as long as we are blessed with being healthy overall, most of us roughly have the same life expectancy. A baby born today in the developed world can reasonably assume to have 80 years in the tank. That’s about 30,000 days. And it’s up to us to make each of those days count. Outsized financial success won’t raise that number by much.
That most of us are given that many days is perhaps the greatest achievement of the modern age. There have been cultures in the past where elites have lived long lives. But the drastically improved life expectancy for the population at large is a fairly new phenomenon. It’s really just a story of the last century.
Social, medical and economic progress made that possible. Many historically important survival risks are essentially gone for most people. There is much less violence today. Safety standards are much stricter. Child mortality is near zero. There are effective medications for many historical plagues.
The result is that most of us have the opportunity today to make it quite close to our naturally given potential. We primarily achieved this through a natural and low cost approach. This approach is close to being fully maxed out. The next logical step is to address mortality with a more sophisticated engineering approach. I doubt that the benefits of that approach can be enjoyed broadly because it will be much more costly and because it coincides with a unique demographic and economic environment.
…to mortality as an accelerator of inequality.
As I have discussed in past articles, our understanding of the human body has started expanding rapidly with the rise of the biotech industry since the 1980s. We started to tackle medicine at a much more foundational level. The primary approach is still to target specific diseases. But it’s also possible to aggregate these disease-specific efforts into a holistic picture. All healthcare R&D ultimately follows one overarching objective: Delay death.
In my opinion, the best way to illustrate that is to refer to The Hallmarks of Aging, a 2013 landmark paper on mortality. In this article (and in a later update), a team of scientists presented aging as 12 categories of biochemical changes that progressively destroy physiological integrity and body function.
Some of these categories are effectively subcategories of others. I have summarized the most important categories below. As you will see, many of them are being addressed right now through commercial R&D efforts, with several themes showing rapid progress and enormous commitment of capital.
Genome instability
Every time our cells divide, there is a chance of unwanted mutations. If too many mutations accumulate, some cells turn rogue. Instead of doing what they are supposed to do, they start sabotaging normal body functions. They become cancer.
The most foundational approach to address this problem would be to edit our genes directly with technologies like CRISPR-Cas. Efforts in this regard are obviously at an extremely early stage. But progress is rapid and this technology promises more breakthroughs in the decades ahead.
More traditional approaches to cancer treatment keep improving as well. Oncology remains as one of the hottest segments in healthcare with vast amounts of capital committed.
Loss of proteostasis
Proteins have important body functions, for example for communication between cells (hormones), as process catalysts (enzymes) or as building blocks for the body. They can only carry out their function if they are folded in precise 3D shapes. As we age, this folding starts failing. Misfolded proteins will then start clumping together into toxic aggregates that prevent the cells from functioning properly. Such protein plaque then causes diseases like Alzheimer’s.
RNA technology is the most direct approach to address issues associated with malfunctioning proteins. RNAs are copies of our DNA used to control the production of proteins. Various companies are currently developing therapies to modify or inhibit wrongful protein production through RNA manipulation. This space is currently heating up without many investors noticing. Alnylam ALNY 0.00%↑ is currently at a $46bn market cap. Have you ever heard of them?
Deregulated nutrient sensing
We have metabolic sensors that inform our cells when to grow/divide and when to hunker down and repair. As we age, these sensors start to malfunction. Repair activity then becomes insufficient. This drives metabolic dysfunction and it leads to diseases like diabetes which then leads to cardiovascular and metabolic failures.
This hallmark of ageing is obviously one of the commercially most relevant themes right now. The obesity drug industry directly fixes nutrient signaling with tremendous health benefits for patients. This industry with a trillion dollar market cap didn’t exist a decade ago.
Cellular senescence
Cells have mechanisms built in that instruct them to self-destruct when they become too damaged to divide safely. They won’t necessarily become cancer when they refuse to do so. Some cells become ‘senescent’ which literally means old. They start secreting toxic chemicals and spread dysfunction through the tissue.
Killing these zombie cells theoretically has great potential. However, the space is currently fairly quiet from an R&D perspective. Trials have so far not shown sufficiently promising results. Something to watch out for with a more long-term view.
Chronic inflammation
In principle, inflammation is a healthy immune response to an infection or injury. However, inflammation becomes chronic as we age because the immune system increasingly reacts to senescent cells, protein debris and other age-related changes. This is called sterile inflammation which over time harms healthy tissue as collateral damage.
Managing the immune system will arguably be central to delay ageing in the future. Its potential is enormous if we can precisely direct it to fight threats while at the same time avoid collateral damage to healthy tissue. Immunotherapy has already revolutionized cancer therapy and it might do the same in cardiovascular diseases and other therapeutic areas.
For example, Novo’s 2023 SELECT trial suggested that semaglutide has anti-inflammatory effects that are somewhat independent from weight loss. There is also potential of repurposing autoimmune drugs for broader use.
Professionalizing dietary and lifestyle management will be big as well to address chronic inflammation. Diets rich in fiber and proteins reduce inflammation.
Being physically active and outdoors does as well. Vitamin D acts as a hormone that modulates the immune system and reduces excessive immune activation. If you are concerned about allergies for your children, send them outside. ;)
Why won’t the benefits accrue to everyone?
Capital intensity
The global pharmaceutical R&D spend currently stands at about $300bn per year. It has grown 8% annually between 2016 and 2024. This is significantly faster than global GDP which has grown 5% annually during that period.
This spending needs to see a return to be justified. There are two main reasons why I doubt the population at large will have the financial resources to afford the products coming out of the global pharmaceutical R&D pipeline.
The first reason is demographics. About 1.3 billion people currently live in what United Nations defines as high income countries. Their income is high enough that they can reasonably hope to enjoy the benefits of current medical R&D.
Now, look at their current age structure:
I am 38. I would have been old AF in most tribes that ever existed. However, today I’m still in the younger half of these people! 59% of us are in productive ages (20-64). This share will likely drop to 50% or lower over the coming thirty years. If longevity R&D surprises to the upside, the share of productive age people will likely fall even faster.
In this context, it will be increasingly difficult to provide high quality medical care broadly. There will be tremendous pressure on healthcare budgets. We will have to negotiate what an additional average year of human life is worth. Many people with a medical need will rely on transfer payments to receive care. Younger generations will be decreasingly able to generate the economic output to enable these transfer payments.
Many healthcare and social security systems are already at or beyond their breaking points today. I wrote about the nightmare of the German system in more detail here:
But the stories coming out of other countries are equally dark. The British NHS is infamous for absurd wait times, even for critical treatments. My fellow Canadians are travelling to the US to get treatment if they can afford it. And Americans are aching under absolutely ridiculous private health insurance costs while Medicare and Medicaid expenses continue to rise rapidly.
The more successful we become at delaying death, the more unaffordable it will become for the majority of people. Let’s say you can realistically work in your job until you are 65 (which is already a stretch). If you die at 75 (which most people did just a few decades ago), you need transfer payments for 10 years. If you live to 105, you need transfer payments for 40 (!) years.
Now, you could of course argue that retirement ages will have to rise. But ask yourself how realistic that is. Which job can you even do all the way to official retirement age today?
This feeds directly into my second point beyond demography: the nature of the labor market. It’s changing structurally for all age groups. Not just for old people, but especially for them.
Every technological revolution redefines what labor means for the majority of people. The more people are doing a job, the higher the pressure will be to automate that job. That was first true for hunters & gatherers, then for farmers and then for factory workers.
The same is now happening for office workers, which account for the majority of the labor force today. Most of what they do is manipulate text and numbers in computers. Some of that will be difficult for AI to disrupt. But much of it won’t. I have argued in the past that AI can’t compete with human reasoning. But the problem is that many jobs don’t necessarily need human level reasoning. Sophisticated pattern matching often suffices.
As in every technological revolution, this raises the bar for humans looking for jobs. Adaptation and more specialization is needed. I doubt that many people are well prepared for that. The education system is utterly unprepared for this disruption and - just anecdotally speaking as a father - the academic performance in school seems to be falling dramatically compared to the past. I don’t know how the majority of today’s youngsters are supposed to make it after school. I worry for them.
Yes, technological innovation creates new types of jobs. But it’s not a given that those jobs raise the bargaining power of those getting these jobs. I fear that the next iteration after the 9-5 office worker will be much worse off in terms of real income and hence ability to afford the latest medical care.
Knowledge gap
It’s not just about what commercial healthcare solutions are out there. It’s also about having the expertise to find the correct treatment and applying it appropriately. This is not a trivial problem. Take GLP-1 for example. There tons of stories out there suggesting that patients either opt out of their treatment or rebound in weight after their treatment.
It’s very hard to evaluate the benefit of a medical treatment as a patient. You don’t see the positive result immediately. Sometimes you don’t see it for decades. Think about how many different ideas about proper nutrition are out there. Compare that to buying a car or a pair of jeans. You know pretty much instantly whether it’s suitable for your needs. Taking care of your jeans is easy. Taking care of your genes is hard.
To navigate this challenging healthcare environment, patients need experts to hold their hand. Modern Value Investing had a great piece touching on that a while ago where he framed WeightWatchers as such an expert handholder.
I don’t know whether WeightWatchers in particular will work as a stock or not. But I’m confident that the overall importance of personal healthcare managers will rise in the future. The more individual their solutions the better. They won’t just manage medical care for their patients/customers, but also their nutrition and overall lifestyle.
In fact, all of this is already happening today. Tech entrepreneur Bryan Johnson allegedly spends $2m per year on his Project Blueprint in which he tries to beat ageing. Billionaires like Jeff Bezos, Sam Altman or Peter Thiel are funding longevity R&D. Athletes like LeBron James, Cristiano Ronaldo, Tom Brady or Novak Djokovic are rewriting what we now about performance maintenance.
Wealthy people will have the time and money to follow their lead. I’m afraid average people won’t.
Sincerely,
Rene