Are you looking forward to age?
How often do you think about what will happen to your mind and body in the coming decades?Once you are in your thirties, you can most likely forget to take up any new sport competitively — but even for moderate sportive activities, your muscles will become weaker, less mobile, and have more trouble recovering from injuries.
At that age, you also have to hurry up if you want to have children as the chance of infertility increases year by year. This declining reproduction ability shouldn’t only concern women, as older men tend to have more mutations in their sperm, leading to a range of potential genetic abnormalities and significantly reduced fertility. (Source)
When you arrive in your fifties, the risks of all kinds of diseases such as cancer, heart disease, and diabetes start to increase exponentially (see graph below). You will also realize that more and more of your friends are dying of these diseases. Just going from 40 to 70 increases your risk of dying from cancer by about 40-fold, heart disease 30-fold, and Alzheimer’s disease by a whopping 300-fold. (Source)
With a more frail body and the experience of losing your friends over time, the risk of depression will more than double, which might further accelerate the decline of the physical health of your body. And apart from physical deterioration and mental health problems, your cognitive performance will likely decline on all levels with worse memory and processing speed.
In the (not unlikely) event that you will survive to the age of 85, your connection to your loved ones and society will also be severely impacted by hearing loss and dementia.¹
The aging of our bodies is the cause of most misery and death amongst the human population. It was estimated that more than half of the global health burden among adults could be attributed to age-related diseases in 2017 and that this number is growing. (Source). Despite this, there is an astonishing lack of funding for research to understand and potentially combat the “climate change of health care” — in the US, for example, less than 1% of the total National Institutes of Health (NIH) budget.
Life mission
Aging is a misery, so in this article I want to share my view on why fighting aging is feasible and desirable. I propose that becoming an “ageless society” should be one of the primary pursuits of humanity in the coming decades.There are now numerous shows, articles, and podcasts on this topic, many launched only within the last 1–2 years. You may find information on fighting aging by looking for geroscience, longevity, rejuvenation, or biogerontology. I am writing this piece to give my perspective on the field
Who am I? I worked in various technology roles and recently left my own startup working on robotic assistants to perform tedious manual work in life science laboratories. Since then, I have reflected on my experiences in founding a software company and pondered deeply on what potential life mission I can contribute towards.
The topic of fighting aging came on my radar again after listening to David Sinclair and reading his lifespan book. I had heard about Aubrey de Grey before but somehow never gave the topic much attention as his character and theories were so controversial amongst my friends working in biology and medicine. When diving deeper, I found numerous scientists backing up the claim that it’s likely possible to slow down aging, such as Brian Kenedy and Joao Pedro Magalhaes, whose content managed to convince me that it might just be possible in our lifetimes.
When talking with friends about stopping aging, just like many other folks, I found the topic to be very controversial at times. One major cause of controversy is the concept of creating biologically immortal beings, a view fueled by ideas such as the Longevity Escape Velocity (LEV). It describes a hypothetical situation where advances in rejuvenation technologies are developed faster than we age (at least 1 year of age reversal in 1 chronological year). While I think the concept is interesting and I also call for an “ageless society”, I would rather spend the efforts and discussions on the actual advancements and see how much we can reduce age-related suffering rather than dreaming of immortality.
Pro-aging trance
For many people, fighting aging sounds outright crazy, impossible, or like a dystopian fantasy of rich dudes. This is not surprising as the most prominent news about fighting aging is either about crazy beauty hypes or “snake oil” scams.The narrative is that aging is an unstoppable force. Hence, “resistance is futile” seems to be a rather popular view among journalists, who completely misinterpret data leading to headlines like “Ageing process is unstoppable”. As professor Matt Kaeberlein retorts: “Ageing process is unstoppable until we do something about it.”
The same narrative is reflected in most pop culture, from crazy practices such as blood boys in Silicon Valley to evil rich people controlling the world with eternal life in Altered Carbon. Usually, these stories focus on a singular pursuit for an eternal life of a privileged minority — going as far back as the Epic of Gilgamesh — instead of a healthy delaying of aging for the masses. I suspect (and hope) that there will be more stories in the future offering a counter perspective, as for example this indie film that is being developed.
Gerontologist Aubrey de Grey’s thesis is that the reason for the resistance to anti-aging research is that most people don’t believe it’s possible and are in a pro-aging trance. They are forced to find interpretations for why aging is good for us, putting potential age reversal in the same category as time travel. The situation is described in this fantastic fable by Nick Bostrom as a dragon that kills around 100'000 people every day, and we have come to accept “that it was part of the very meaning of being human to end up in the dragon’s stomach”.
My hypothesis is that most people would agree on spending more time & resources if they believed it would be possible, which is backed by several studies; two examples:
- When guaranteed mental and physical health, 797 of 1000 people wanted to live to 120 or longer (source)
- A majority (65%) of American adults endorse research supporting life extension (source)
So if this article helps even just one person to wake up from the aging trance, I am delighted to have written this article
What is the goal?
There is the ancient myth of Tithonus in which the goddess Eos asked Zeus to make Tithonus immortal but forgot to ask as well for eternal youth. Tithonus lived forever, but his body would become crippled by age, making him beg for his death — this is often called the “Tithonus Fallacy” or “Tithonus Error”.
The goal of fighting aging is not to live forever in an old body but to live as long as possible in a young one — maintaining peak performance as much as physically possible.
While death will probably be inevitable for centuries to come, we can still try to extend the period in which we live healthily — called healthspan. For the development of effective interventions, I believe we should see the maximum years — called lifespan — as a by-product of our efforts and not the primary target. That said, I find it unlikely that improving healthspan would not also improve lifespan.
So what does it actually mean to work on improving healthspan? Between 1900 and 2010, the leading causes of death in the USA have shifted from a majority of deaths (53%) being caused by infectious disease to a deadly combination of heart disease (33%) and cancer (32%) (Source). So it’s easy; we just focus on fixing these, right?
Unfortunately, it was estimated back in 1990 that curing all forms of cancer would increase the life expectancy for a typical 50-year-old woman in the United States by only 3–4 years (Source, also for the plot below). Even with all cardiovascular diseases, cancer, and diabetes fully cured, we are only looking at a lifespan extension of around 16 years.
Why is this the case? It is because the risk to develop any of the known lethal diseases increases by a thousandfold between the ages of 20 to 70 (Source), so even if we are able to cure one disease after the other, there will always be another one coming to get us.
This property of human mortality also explains the fact that while the median age has moved from 50 years to over 80 years between 1840 and 2000, the maximum recorded lifespan has barely moved (see graph below)²
So what is the solution to this misery? We need to find the common culprit causing the exponential mortality, which, according to the “geroscience hypothesis”, is a set of foundational biological mechanisms of aging. 40 years after the start of the war on cancer, we now need a war on aging.
A new norm for preventing diseases becomes even more important if you consider that drug development costs seem to double every nine years (Eroom’s law) and the search for treatments of common diseases such as Alzheimer’s disease has shown a failure rate of nearly 99.6%.
If you are a proponent of fighting age-related diseases, like cancer or Alzheimer’s, consider that targeting aging itself might be the best approach. The most significant difference to traditional medicine in aging research will be that we will focus on people’s general health by intervening in age-related processes instead of waiting until they become sick and frail (also jokingly called “sick-care”).
Is it possible to become ageless?
So far, we have talked about the apparent observable effects of aging on our bodies (some of its “phenotypes”), why we haven’t done anything about it, and how combating aging might be the only solution to live a longer, healthier life. The obvious next question is if it’s even imaginable that we can fight this dragon or if we better just give up on this pointless mission.The most straightforward way to assess the feasibility is to look at nature. Several living organisms outlive humans by millennia. The oldest known living plant individual of King’s lomatia has been dated at least 43'600 years.
Another example of a seemingly non-aging plant is the bristlecone pine that has been estimated to live up to more than 4'000 years. Similarly, fungi such as Armillaria Ostoyae show age estimates ranging from 1900 to 8650 years.
When analyzing animal longevity, the picture isn’t as impressive, but we still find species that show considerably longer lifespans. A long-lived invertebrate example is the Ocean Quahog, with a maximum record of 507 years. Getting closer to our evolutionary tree, Greenland sharks are the longest-lived vertebrates with a lifespan of at least 272 years. Finally, bowhead whales are considered the longest-lived mammals, with individuals being reported to clock 211 years.
In addition to massive differences in mortality between species³, even the same species can change their aging rate drastically through evolutionary changes. For example, smaller dog breeds can live as long as 15 years, while larger dogs such as Saint Bernards only have a maximum lifespan of 8 years.
As explained in previous chapters, we humans experience an exponentially increasing risk of death over time due to aging (known as Gompertz’s law)⁴, and while this law seems to hold for other species such as mice or honey bees, it doesn’t seem to be an ingrained law of biology, as some species are speculated to be biologically immortal (also called negligible senescence) — meaning the rate of mortality is stable or decreasing, as opposed to increasing.
Proving that a species is biologically immortal is impossible, though, as aging could always kick in at a later stage. But if we can pursue long-term studies that continuously don’t find any indication of an aging pattern, that can give a strong signal that it might indeed be possible. This is the case for the simple, jellyfish-like organism, the Hydra, for which researchers didn’t find any senescence pattern in a four-year study in 1998 and an eight-year study in 2015.
For other impressively long-living animals, we are still at the beginning of our research journey; for the Greenland shark, we simply don’t have enough data, and for the resilient naked mole-rat, scientists have intense discussions ongoing, for example. There is still a lot to uncover from our animal friends, and more and more researchers are turning to nature for inspiration in the spirit of Biomimetics.
Note that if we look at the cellular level, the case for biological immortality is more evident.
The famous human (cancerous) HeLa cell line is known to be immortal in the sense that, given the right environment, the cells will divide indefinitely without any observable (further) damage. In addition, our stem cells must be immortal as they have reproduced indefinitely since the beginning of life — recently, this was explained by a rejuvenation event happening in the embryo (Source).
Another way to analyze the feasibility of slowing down aging is to look at successful experiments. Conclusive results have so far only been achieved with animals, as humans live for too long to have effective trials to measure differences in health- or lifespan.⁵
Luckily, numerous experiments in the last decades have shown conclusively that biological aging is at least medically delayable in animals. For example, the record of any lifespan intervention is a mutation of a single gene in the most studied worm on earth, C. Elegans; the resulting lifespan increased tenfold! You can find a whole database of tested drug interventions in the DrugAge database and Laura Deming summarised the data on mouse studies on her website.
A new type of drug categorized as “Senolytics” shows the striking difference in health that is possible through therapies that target aging. Developed at the Mayo Clinic in 2016, it has been shown to extend the healthy lifespan of mice by up to 30%.
It is clearly possible to slow down aging in animals — but what about the timing of the intervention? Contrary to popular belief at that time, it was shown that the popular compound Rapamycin (FDA-approved for organ transplants to prevent immune rejection) increases maximum lifespan by at least 9% even when taken late in life, roughly equivalent to a 60-year-old-person. (Source)
A notorious problem in drug discovery is that many experiments working on “animal models” fail to have the same effect on humans. Hence, the results are always to be taken with a grain of salt. However, successful animal trials still increase the likelihood of success — especially if the mechanism is well understood. Indeed, most if not all drugs approved for human use came from particularly promising animal model research. (Watch this great talk by Dr. Jan Gruber)⁶
As mentioned, there are no conclusive experiments for Humans yet (that I am aware of). Still, there are several clinical trials ongoing, and it seems likely that we will have another breakthrough moment in 1–2 years that yields strong evidence that slowing down aging is possible (also check the excellent Rejuvenation Roadmap):
- The Targeting Aging with Metformin (TAME) trial will test whether metformin can delay the onset of multiple diseases of aging simultaneously ($75 million, 6-year trial beginning 2021)
- Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL): 200 participants over 12 months testing four different Rapamycin dosing regimens.
- TRIIM-X Trial: Testing a combination of growth hormone (somatropin), metformin, and DHEA, following up on the success of the previous TRIIM trial that gave first hints that biological age in humans can be reversed
A famous example of this was the widely publicized experiment by David Sinclair’s lab that used “epigenetic reprogramming” to drive damaged optic nerves to restore themselves, effectively rejuvenating the cells. (Source) Given that both our understanding and the surrounding technologies for gene editing evolve rapidly, this is a very exciting field; recently, Intellia announced that they can already edit genes directly in patients via the CRISPR technology, for example.
In summary, some animals age considerably slower, certain organisms are biologically immortal, and we can slow down aging in animals in laboratories worldwide. We are also already testing interventions on humans. Given the evidence and developments, it seems pretty likely that we will have various technologies at our disposal to slow down our aging process within the coming decades — and maybe even become an ageless society.
Lastly, the more we believe in this mission and the more urgency we can apply to ourselves, the less we will suffer from aging in our future.
Explosion of Interest
Given the developments in the aging field, the interest has exploded in the recent 4–5 years, at least compared to previous decades. Most of my favorite science YouTubers created pieces on slowing/ending/reversing aging, which initially sparked my interest as well; Kurzgesagt (Part 1, Part 2), ColdFusion, and Veritasium are all excellent to watch. Major television channels, such as CNBC, are also airing shows on the topic, although they can not resist the usual lurid headlines.
On the political spectrum, the problem of an ever-increasing aged population — more than 2 billion people 60 and older by 2050 — has been recognized worldwide through specific programs by the World Health Organization (WHO). However, these programs, such as the UN Decade of Healthy Ageing, usually only look at traditional care systems and don’t consider targeting aging as a disease.
Luckily, historical changes are on the horizon, as the UK just mentioned “Addressing the underlying biology of aging” as a primary mission target of their 10-year strategy for the life science sector (Source). More and more advocates for longevity research are entering the political realm and joining initiatives such as the European Longevity Initiative. Stanford was already thinking one step further and created a design challenge for “longevity-ready environments”, how physical spaces should be designed for humans that live for more than a century.
The promise of longevity research hasn’t escaped investors. Michael Greeve, a well-known German investor, invests 300 Million EUR into “rejuvenation” startups (check his presentation). Sergey Young built the 100 Million USD Longevity Vision Fund (also gave a cool talk). This influx of capital is matched with an ever-increasing number of companies working in the field, which you can find on this or that list.
Another notable development was the biggest fundraiser ever towards the Strategies for engineered negligible senescence (SENS) foundation. The blockchain community donated over 20 Million USD within the so-called “PulseChain Airdrop”.
Personal involvement
Investigating the state of anti-aging research and commercial offerings opened a Pandora’s box of content, ranging from crazy biohackers to shady supplement companies. It is even more paramount in this field than in others to have a clear focus. I want to focus on technologies that, in combination, have the potential to radically extend our healthspan, let’s say at least 50%+. It seems like currently available lifestyle interventions (exercise, food intake, limiting drug abuse) and drugs on the horizon (rapamycin, metformin) might buy you 10–20 years of median life expectancy. That’s certainly nice and useful, but I hope we can work on a clear roadmap to significantly more healthy years.⁷An alternative to stopping the biological aging of our bodies would be to stop caring about our biology and just upload our minds to some artificial neural network. Or, instead of developing technologies in our lifetime, we can freeze ourselves through Cryonics and hope a future civilization will resurrect us. I consider these futurist approaches too far out (if ever possible) to be relevant for my life or others currently alive.
So what do I want to work on? I think that possibly the biggest accelerator to aging research both in academic settings as well as for citizen scientists is a good toolset of measuring biological age (Great summary of current aging clocks), which are also approved by regulatory bodies. As Celine Halioua writes in her article, one of the biggest problems in the aging field is that it’s unclear what the endpoints for an aging trial are and that entrepreneurs must usually look for “proxy diseases’’ to measure efficacy against.
There are already commercially available clocks (e.g. myDNAage), but they have to become cheaper, more accessible, and better researched.
Once we can measure biological age, the effect of interventions can be analyzed much more effectively. On a massive scale, individuals can effectively do self-experiments with compounds generally recognized as safe (GRASS), and “biohackers” will actually start hacking instead of just guessing based on feelings and looks.
A great example of a company built with these concepts is Humanity, which uses a combination of so-called “digital biomarkers” (such as heart rate and walking speed) and genetic and blood tests to estimate your biological age and correlate it with lifestyle and supplement choices. (Note: No endorsement from my side, didn’t try their app yet)
The activities in the coming months from my side will be:
- Keeping up with longevity news, educating myself, and writing articles about my journey (will be linked to the ageless society publication)
- Helping to create a centralized knowledge base for longevity research at Longevity Wiki, as this will be paramount for any effort
- Joining communities and conferences, currently following VitaDAO, for example
- Finally, my goal is to find a career in the longevity space combined with my technical know-how in software development and automation/robotics — pointers welcome
TL;DR Aging sucks, aging can be slowed down or even reversed — let’s try it!
[1] Admittedly, this description draws a very bleak picture and is also compiled just from the negative statistics I found — positive aspects include that it seems like older people, despite all the circumstances of aging, show the same happiness as younger ones (Source)
[2] In the US, the average life expectancy recently even declined (Source)
[3] There is ongoing research into why the lifespan between different species varies so much, see for example this interesting project
[4] Interestingly, the mortality rate actually stabilizes late in life, but obviously at a number too high to be desired (Source)
[5] This can be solved by using clocks such as the Epigenetic clocks, which will be discussed in another article
[6] When analyzing medical studies, one needs to be aware of the “Mouse Trap”; baseline data might be wildly skewed because the control group of animals is unhealthy. For example, drastic life extension achieved with caloric restriction can just mean that the control group was overweight
[7] With regards to already possible lifestyle interventions, there is quite some research analyzing “Centenarians” (People over 100 years of age) who are found with the highest concentration in the so-called “Blue Zones”
