The most important things to know about aging.

I believe the field of aging research is in a similar place as driverless cars were around 2004. By that time universities like Carnegie Mellon had been researching the concept for a decade and the U.S. Defense Advanced Research Projects Agency (DARPA) had begun funding competitions to accelerate progress. It would be another 5 years before Google would launch its driverless car business - Waymo - in 2009, and catalyze awareness that it was no longer a question of if, but when they were coming. My best guess is that the general public will be converted to the belief that it is only a matter of time until aging is cured somewhere around 2027-2032. However, there is a big difference between driverless cars and aging.

Belief in the inevitability of driverless cars has had minimal influence over local and geopolitics, and it has not engendered passionate and combative debates among politicians and the general public. Aging will be different. When the paradigm shift about aging finally reaches critical mass the world will start to change very quickly. It will be something everyone talks about all the time. Politicians will make aging research the cornerstone of their campaigns. Others will stake their careers on making sure it never succeeds. Geopolitical conflicts will become a side-show relative to the focus given by countries to the debate around what to do about aging.

This post will touch on the science and introduce some people and places for you to dig further if interested, but mostly it’s about the big questions that have come up repeatedly over the countless conversations I’ve had with people about aging. Unlike my other posts, this post does not need to be treated like an essay. You can read section 1, 5 and 7 if those are the questions that interest you. There is no over arching theme, or messages that require reading the whole post to capture. Each section is designed to stand on its own and provide an answer (or at the least, key considerations) to one specific question. So, feel free to read straight down the list, but also feel free to jump around and just read the topics that interest you.

Over time I intend to keep adding to this. Whenever I come up with a new interesting topic I will add it to the Table of Contents - this will let you know that it’s on my list to address. However, only the items that are bolded in the table of contents have already been addressed below, everything in italics are topics I have on my list to add in the future. If you have any suggestions for topics to cover, better ideas about how to address a topic than I have below, or interesting research or content that you think would fit into this post please send it to me via comment, email or by finding me on twitter (@01core_ben).

Now on with the post.

Table of Contents:

1. Isn’t trying to cure aging - a natural phenomenon - an attempt at playing God?

2. I don’t want to live forever in the decrepit body of a 100 year old.

3. Is Aging Curable?

4. Humanities’ long history of thinking that totally fucked-up things are completely normal.

5. Aging is the number one cause of pain and suffering and it’s not even close.

6. Nobody dies of old age anymore and this is a problem.

7. If people stop aging won’t the world become over-crowded and/or run out of resources?

8. Is death an effective motivator for human progress, without which humanity would stagnate?

9. Will governments try to stop aging research or will they support it?

10. Won’t treatments only be available to the rich?

11. What are some of the craziest aging treatments we might see first?

12. Does cryogenic freezing have a shot at working?

13. Thoughts on the clone and consciousness transfer equivalence.

#1 Isn’t trying to cure aging - a natural phenomenon - an attempt at playing God?

First, let me point out that there are many “natural” things humans have fought against, including:

• Cystic Fibrosis

• Spinal Muscular Atrophy

• Polio

• Cancer

• Alzheimer’s

• Cholera

• The Bubonic Plague

• Macular Degeneration

• Black Mamba Venom

• You get the point…

Are anti-venom, chemo-therapy and wearing glasses attempts at playing God? Is vaccinating against polio an attempt at playing God?

If “playing God” means altering the natural order of things, then humans (specifically, hominids) have been playing God for at least 300,000 years and maybe up to 1,000,000. This is the timeframe of possibilities for the earliest use of fire.

Neanderthals played God by painting caves with red hand-stencils 64,000 years ago, forever altering the naturally khaki-colored walls. Homo Sapiens followed suit at least 45,000 years ago. Not Satisfied with this answer? Let’s keep going.

Farming started around 12,000 years ago, but farming was pre-dated by hunter gatherers pro-actively spreading seeds to accelerate the growth of fruits and other edible foliage. Surely farming is an alteration of the natural order of things. After all, farming is what enabled humans to live in extraordinarily dense populations and hence take over the world. Let’s keep going anyway.

Around 5,000 years ago Egyptians were not entirely satisfied with the natural location of their water, so they started digging canals.

A question is begging: what is natural? Are man-made physical structures natural? Is art natural? Is disease natural? Are wounds caused by accidents natural?

The earliest examples of amputations date to 31,000 years ago. If a foot had been bitten by a Black Mamba and the poison was spreading, was the poison natural? Should humans have intervened? Why not just stand around and watch the poor soul die from the natural order of things?

Humans have been interfering with nature for as long as we’ve been around. We never succeeded in building a Tower of Babel but SpaceX does regularly send people to the heavens. Today people are actually spending money to figure out how to clean up space trash. We humans have launched so many artifacts (satellites, etc) into the heavens that we need garbage people to clean it up so that our satellites and space station don’t accidentally run into them at tens of thousands of miles per hours.

If humans were like every other animal then anything they did would be considered natural. Because we’re not like every other animal people tend to believe that everything we do is un-natural.

I don’t think there’s much value to the debate of what’s natural and what isn’t. The important point is that humans have been striving to make their lives better for countless millennia, and that’s a good thing. It’s what makes us human!

The purpose of healthcare should be to keep people healthy and happy for as long as possible, even if that means a reallllly long time…

Let me fill you in on a secret: it is impossible to cure diseases without curing aging. Let me state this again in a different way because it’s important to understand: If humans cure all diseases, they will have cured aging as a bi-product. The two are inextricably linked. Aging might be cured without curing all disease, but you cannot cure all disease without curing aging by default.

When you hear me reference a “cure” for aging, I’m not talking about a single pill or treatment. I’m using the term cure as a catch-all for the combination of treatments that will collectively allow us to stop and reverse aging. In essence, each of these treatments will be fighting against one “disease”, and collectively they will be a cure.

#2 I don’t want to live forever in the decrepit body of a 100 year old.

This is the most common “gut reaction” I get when introducing the topic of dramatically longer lifespans to people (sorry folks, you aren’t the first person to make this joke). Nobody is asking you to live forever in an old body. While it is likely that in the very beginning our first treatments will delay or slow the aging process, an outright cure doesn’t mean you get frozen in time at whatever age you happen to be - it means you get to pick your biological age. A cure for aging means we have essentially figured out how to program the human body. If you get tired of living then it will be your right to end your life, but for as long as you are alive you will be in the body of a healthy 26 year old.

Here is a graphical representation of what a cure would do to our quality of life curve over time (it might be more accurate to call it a Quality of Health Curve):

I often hear that people don’t want the burden of “choosing when they die” - which is what would have to happen if they didn’t age or fall victim to a catastrophic accident right? Not really. Feel free at any point to stop taking the treatments that keep you from getting cancer, Alzheimer’s, dementia, etc. When you do succumb to one or more of these diseases, sign up for hospice and let nature do the rest. You will have options beyond forced suicide… In practice, by the time we have cured aging there will be many people interested in removing the burden of choosing when to die and I expect the free market to come up with creative solutions.

#3 Is Aging Curable?

George Church thinks it is. Recognized by Time Magazine as one of the 100 most influential people in the world, Church is widely considered to be the “Founding Father of Genomics” and is one of the world’s foremost experts on personal genomics and synthetic biology. He is a professor at both Harvard and MIT and runs a research lab at Harvard which has spawned dozens of biotech companies over the years. He is on record stating that gene therapies capable of slowing or reversing the aging process could hit the market by the 2030s. This isn’t such a far out idea. Gene therapies attempt to do one of four things:

1. Replace missing genes

2. Put in new genes

3. Delete genes

4. Turn genes on/off (just because you have a gene doesn’t mean its expressed)

Gene therapies already exist. Zolgensma is one such therapy used to treat spinal muscular atrophy (SMA) - one of the most debilitating diseases on the planet. It works by replacing missing or non-functional SMN1 genes at a cost of $2m. Interestingly, as George Church explains in this interview, the technology used to deliver Zolgensma is very similar to that used to deliver the Covid-19 mRNA vaccine, the implication being that costs will come down over time ($2 is the estimated delivery cost of an mRNA vaccine for Covid) as the number of people receiving treatment grows and the R&D dollars can be amortized over a larger population.

The results have been remarkable and gene therapies in the future will only get better.

The trickiest thing about gene therapies is that genes can have multiple functions & multiple genes can work symbiotically to perform a single function. For example, there are around 15 genes known to impact eye color. It isn’t safe to mess with any particular gene until you understand the interactions between that gene and the other 20,000+ genes we have. Fundamentally we have the tools, it’s just a matter of spending the time and resources required to figure out these interactions. Advances in machine learning and AI will surely help, as they have recently with the decades old problem of predicting protein shapes - which was finally cracked by a company called Deep Mind (owned by Alphabet).

Studies like this aim to figure out which genes are associated with extreme longevity (living past 100). Two things impact our lifespans: genes and experiences (nature and nurture). Obviously healthy living isn’t enough to get to 110 years old or more people would make it. Genes are playing a role. Once we figure out what those genes are (or aren’t) we’ll have everything we need to start gene therapy trials. The first treatments won’t be cures but they will buy us time.

I want to make a point here. In section #2 above I made the comment: A cure for aging means we have essentially figured out how to program the human body. In-vivo gene therapies ARE “programming the body”. Our genes are like the operating system a computer runs on. A computer getting a virus is very similar to a child having a broken SMN1 gene. So, we are already today re-programming.

Another person working hard to cure aging is Arthur Levinson. Levinson is the current chairman of Apple, and the CEO of a company founded by Alphabet called Calico. Before Calico Levinson was the CEO of Genentech from 1995 to 2009, a company he lead until it was sold to Roche for $47 billion. Here is a link to Calico’s leadership team. Calico says their goal is to “develop new interventions aimed at aging and age-related diseases.”

Altos Labs is the newest and highest profile presence on the “aging is curable” scene. They just broke records by raising a $3billion seed round. Their leadership team is as impressive as Calico’s. Hal Barron is the CEO and a co-founder. Prior to Altos he was President and Chief Scientific Officer of R&D at GSK, a $57billion biotech company. The rest of the executive and scientific leadership reads likes a “Who’s Who” of biotech, pharma and academia.

Calico and Altos have been able to attract dozens of the world’s brightest minds across fields including biology, chemistry, physics and AI. These are not groups of mad scientists operating on the fringe…

Here’s a great talk given by Robert Signer, Ph.D., and Shiri Gur-Cohen, Ph.D., two professors from the University of California San Diego about the potential of programmable stem cells. Robert’s talk is at the beginning and starts off with a slew of fascinating statistics, including many on the economic consequences of aging.

If you’d like to go further down the rabbit hole there are two books which will get you started. The first is Ageless: The New Science of Getting Older Without Getting Old:

Scientists, on the other hand, know that aging is not a biological inevitability. Ageless introduces us to the cutting-edge research that is paving the way for a revolution in medicine. It takes us inside the laboratories where scientists are studying every aspect of the body: DNA, mitochondria, stem cells, the immune system, even ‘aging genes’ that have helped animals enjoy a tenfold increase in lifespan - and which could, in the not too distant future, lead to treatments which could forestall our own bodies’ decline.

Ageless was written by Andrew Steele. Andrew was a physicist with a PhD from Oxford before switching his focus to computational biology. Now he is a full time science writer and authority on the most cutting edge research happening around aging.

The second book is called Lifespan: Why We Age and Why We Don’t Have To. It was written by David Sinclair, a professor at Harvard Medical School and codirector of the Paul F. Glenn Center for the Biological Mechanisms of Aging. David has also been recognized by Time magazine as one of the 100 most influential people in the world.

Another path down the rabbit hole is to just start googling “University Name (e.g. Berkeley) + aging research”. You will find that virtually all major universities have established departments focused on aging.

The fact of the matter is that credible scientists have stopped debating whether aging is curable. The only thing they debate now is the timeline…

#4 Humanities’ long history of thinking that totally fucked-up things are completely normal.

The only reason aging isn’t perceived as the most horrific atrocity ever to befall humankind is because it has been a fact of life since the beginning of time. That said, for all of history humans have been totally fine with things that we in the present look back on with horror. Here are three examples.

It was common practice for Ancient Greek nobility to engage in the practice of pederasty. Pederasty in Ancient Greece was the practice of an adult male engaging in a deeply meaningful but also sexual relationship with a pubescent or adolescent boy. In these relationships the adult male (called erastes) was a trusted mentor of the adolescent (called eromenos). The family of the eromenos saw it as a great honor to have their son attended to and groomed by a member of the Greek nobility, and nothing was done without the strict approval of the eromenos’ father.

These relationships didn’t last long and were seen by society as a “coming of age” or “rite of passage” ritual. The eromenos himself might not have been thrilled with the sexual aspect of the relationship, but at worst they would have seen it like a hazing ritual they needed to tough out to become a member of a prestigious fraternity. Undoubtedly when the eromenos himself became a father he would have sought out an erastes for his own son.

The following two images are of famous Greek artifacts illustrating the practice of pederasty:

Women (girls!) at the time usually had their arranged marriages consummated between the ages of 12 and 16. Different times eh?

Bloodletting. People debate what illness (or illnesses) the United States’ first president George Washington caught that led to his death, but everyone knows the proximate cause was a loss of blood. “Bloodletting” to rid the body of bad humors was a standard of care for over 3,000 years. Doctors bled an estimated 40% of Ole’ Georgy Boy’s blood before he finally died.

Doctors slinging cancer sticks. This is one of my favorites.

What causes humanities’ perspective to change? Why did child brides seem okay in the past but not now? Why did bloodletting last for 3,000 years? Why were doctors permitted to promote cigarettes?

Simply put, past horrors were made possible by a lack of information. Once things become understood our opinions about them change. New information leads to the updating of belief systems. Unfortunately information doesn’t go from zero to 100 overnight. Instead it spreads like a virus with varying degrees of contagion, held back by the joint immunities of inertia and prior belief paradigms.

In 1828 Pierre Charles Alexandre Louis was one of the first physicians to openly criticize bloodletting, but it wasn’t until the late 19th century that it was widely discredited.

Humans will look back on healthcare in the 2020s with the same horror that we look back at blood letting. Our healthcare system today will be seen as unfathomably primitive. You mean to tell me you fixed diabetic foot ulcers by amputating? (130,000 per year in the US alone) You mean to tell me that the standard of care for treating cancers was to just try and kill a bajillion of the body’s cells indiscriminately (chemo)?

#5 Aging is the number one cause of pain and suffering and it’s not even close.

An age curve chart shows you the incidence rates for various diseases across different age ranges. Here is the age curve chart for all types cancer combined:

From Cancer.gov: Advancing age is the most important risk factor for cancer overall and for many individual cancer types. The incidence rates for cancer overall climb steadily as age increases, from fewer than 25 cases per 100,000 people in age groups under 20, to about 350 per 100,000 people among those aged 45-40, to more than 1,000 per 100,000 people in age groups 60 years and older.

According to the most recent statistical data from NCI’s Surveillance, Epidemiology and End Results (SEER) Program, the median age of a cancer diagnosis is 66 years old.

The median age of a breast cancer diagnosis is 62. Here is the aging curve:

The average age that someone is diagnosed with Lung Cancer is 70 years old! Here’s the aging curve:

Are these age curves unique to cancer? Hardly. Here’s the aging curve for Dementia (which includes Alzheimer’s):

The chart doesn’t even start before the age of 60!

The curves look the same for: heart disease, chronic respiratory diseases, stroke, flu and pneumonia, nephritis (kidney disease), diabetes, blindness, loss of hearing, limb amputations, and even the severity of Covid-19. In case you’re wondering, this list includes ALL of the top causes of death except for “accidents” which is number 4.

The data is unequivocal. You don’t need a deep grasp of the biological science of aging to know that it is the primary cause of disease and suffering - you just have to be able to interpret a graph.

#6 Nobody dies of old age anymore and this is a problem

In the western world people stopped dying of old age around 1951.

The following excerpt is from a letter written by Scott Sattler, a doctor who received his medical degree from Stanford and now lives in Eureka, CA. He wanted to get “Old Age” back on the death certificate.

It turns out that as a country we eliminated dying of old age back in 1951 when a federal Public Health Conference on Records and Statistics standardized causes of death throughout the nation and defined 130 acceptable diagnostic causative conditions. Old age was specifically omitted… The World Health Organization, impressed by our nation’s success in conquering old age as a cause of death, soon adopted this same policy, thus making it essentially impossible to die of old age anywhere in the civilized world…

It’s time we move on from the currently embraced 1951 mentality surrounding death. It’s time to put “Old Age” back on the books and into the research arena as one of the essential causes of the physical body’s demise. Maybe if we gave it a sophisticated title it would be more acceptable, like “Ordinary [O] Legitimate [L] Death [D] - Apoptosis [A], Genetically [G] Encoded [E].” Then we could just use the acronym.

The letter is worth reading in full.

Scott believed there were three reasons it was important to keep “old age” as an option on death certificates:

1. The science supported it. He lists genetically programmed cell death and other examples that have been strictly tied to aging.

2. Without it physicians are forced to write in something else for cause of death. He lists as one example a 107 year old who died of “heart disease”, which is one of the common go-to responses physicians use when there isn’t an obvious alternative. This matters because research and medical funding dollars are allocated in part based on cause-of-death statistics.

3. People are more likely to push their relatives (or themselves) to take drastic measures (surgery, chemo, etc) to fight a “disease” even when it’s obvious there is no hope, whereas accepting that it’s time for palliative care is far easier if there is no enemy, just the natural aging process.

While the amount of funding being allocated to aging research is growing exponentially, it is still just a rounding error compared to total healthcare R&D.

There’s another important point to make here. If aging is not designated an official disease then it won’t be covered by insurance. If insurance doesn’t cover something then the market is limited to “out-of-pocket”, which is barely a blip by comparison.

Is it such a stretch to add “aging” to death certificates? Not really.

The below image is from the guide on how to fill out a death certificate in Florida, published by the Florida Department of Health Bureau of Vital Statistics.

I’ve highlighted the key instructions in red. Basically, the directions currently state that you are supposed to list the most direct cause of death, then any underlying conditions that lead up to it. In the case of their example a “Rupture of myocardium” was caused by an “Acute myocardial Infarction” which was caused by a “Coronary artery thrombosis” which was caused by “atherosclerotic coronary artery disease”. All four of these problems will find their way into the statistics aggregated in Florida and across the United States.

Another example - in layman’s terms - of someone who died of lung cancer might state: “asphyxiation” was caused by “fluid buildup in the lungs” which was caused by “lung cancer”, which was caused by “a combination of tobacco inhalation and the general deterioration of the human body from aging”.

Given our age curve data, is it so unreasonable to add an additional line that attributes lung cancer or coronary artery disease to aging? I’m not saying aging should be on all death certificates, but why not list it for any death that is attributed to a disease where 80% of the sufferers are over the age of 60? Surely if 80% of the sufferers of a disease are over 60 then age is the primary underlying cause…

#7 If people stop aging won’t the world become over-crowded and/or run out of resources?

This graphic is a little outdated but the point stands. The world doesn’t have a space problem:

The graphic shows how much space within the United States would be occupied if 6.9 billion people were living with the same population density as various cities. For example, if the entire world lived in a city with the population density of New York, then that city would be the size of Texas.

What about resource scarcity? Won’t the world run out of natural resources?

Various humans have had this fear at least since the time of Thomas Malthus in the 1700s. A little bit of deductive reasoning tells us that we have nothing to fear though.

The only input you need to have an abundant supply of virtually any resource, and certainly food - is energy. I found this interesting post on landartgenerator.org which calculates how much space would be required to satisfy 100% of the world’s energy needs with solar panels. Here’s an excerpt:

According to the US Department of Energy, the world consumption of energy in all its forms is projected to reach 678 quadrillion Btu by 2030…Converting energy demand into kilowatt hours and assuming a conversion of 400 kWh per square meter (calculation in link) we can calculate that we would need an area roughly equal to the size of Spain (496,805 square kilometers). Let’s put this in perspective.

According to the United Nations 170,000 square kilometers of forest is destroyed each year, if we constructed solar farms at the same rate, we would be finished in 3 years.

There are 1.2 million square kilometers of farmland in China. This is 2.5 times the area of solar farms required to power the world in 2030.

Here’s a graphic:

You can barely even see the little boxes…

Abundant energy would give us unlimited water (desalinizing the ocean) and hence unlimited food. Abundant energy is possible, it’s just an issue of getting the investment. So far humans haven’t needed to make this investment, but when we do we will, the free market and politicians looking to keep their jobs will make sure of that.

MORE QUESTIONS WILL BE ADDED OVER TIME, PLEASE CHECK BACK EVERY FEW WEEKS!

#8 Is death an effective motivator for human progress, without which humanity would stagnate?

There are a few different ways to go about addressing this question. One could easily make the argument that it’s an incredibly selfish viewpoint to believe that the many tens of billions of humans to exist over the coming centuries should have to suffer and die so that people in the future might have fancier gadgets and faster spaceships.

But the best argument is the most logical one. Cracking immortality will come in a near-AGI or post-AGI world.

If humans have already figured out how to create artificial intelligence on non-biological (or synthetic) substrates - then we humans in our meat bodies will not be the ones driving progress - it will be the machines.

The people who make the doomer argument that death is the fuel for motivation are not making the argument that humans would lose all interest in progress if we weren’t racing against the clock of life. They’re making the argument that putting in insane work hours requires a level of motivation that might not exist without a fear of death.

IF human effort will be required to make progress in the future it will not be the kind that requires 80 hour workweeks. Rather, it would be more in the form of guiding and suggesting to the artificial intelligence what it should work on. Effort that hardly requires a fear of death for a catalyst.

#9 Will governments try to stop aging research or will they support it?

China has recently moved from a 1 child policy to a 2 child policy to a 3 child policy.

South Korea and Japan see declining populations as one of the biggest threats they face.

A country's power is in no small part dependent on the size of it's population.

The health of a country's balance sheet is largely a function of the ratio of that country's Working Population (taxpayers) to Retirees.

In a world where people can move freely - is there any situation whereby people don't migrate to the place that enables them to stay healthy?

When it becomes obvious that a cure for aging is coming - what percent of the population is going to vote for the politicians who want to make pain and suffering optional?

Imagine there are two people running for president, one wants to enable you to live in the body of a healthy 26 year old for as long as you desire - the other wants you to spend your last decade in a retirement home, incontinent, immobile and in pain.

We'd see the biggest landslide in history.

All of the incentives - both economic, personal and humanitarian - point in the same direction. Governments will not only support a cure for aging - when the time comes they will be providing the funding that turns the effort into a full-scale MOONSHOT.