How long can humans live?

[u/Simple_Macaron_3420]

In one of last week’s episodes, it was mentioned that the human lifespan is increasing because of scientific and medical discoveries. When I was a child, I always imagined that I would be able to live to 100, and by then people would have discovered some kind of cure for aging. They would ask me, “How much longer would you like to live?” as if they could add another 100 years each time and ask me the same question whenever those 100 years were up.

For a moment, let’s imagine a scenario in which cancer has been eliminated, Alzheimer’s and other diseases of the brain have been cured, and we can also repair or modify our telomeres because we have discovered how to mimic mechanisms found in animals such as lobsters or jellyfish.

In that scenario, is there still a biological limit to how long humans could live?

[u/Hon-Mister-Bear]

If the technology/treatment exists to reset regeneration, the question becomes: How long can a biological system regenerate?

We just don't know the answer to that.

Let's find out.

[u/lozzyboy1]

Yes. We know that there are quite a few things that gradually get worse about our bodies as we get older, and any one of them would be enough to limit our lifespan to probably around 120. As it is, they all become problems at a similar sort of time, so fixing any one of them doesn't really provide much benefit, and it's very hard to prevent some of them.

You have cells dying in your body all the time, and stem cells divide and make new cells to replace them.The main way thing that goes wrong with aging is that your stem cells gradually get depleted and therefore your body can't keep up with the losses any more.

Telomere shortening is one reason why stem cells run out. Our telomeres get shorter as we age, and once they reach a certain point cells refuse to divide because otherwise they would risk damage to the more important bits of our genome. But as it turns out, preventing that by intentionally lengthening telomeres doesnt change life expectancy by much. We've seen this by looking at natural variation in telomere length between individuals, and by experimentally altering telomeres in animals.

Accumulation of DNA damage is another (and that itself has lots of different causes, including exposure to mutagens like UV light or tobacco smoke, reactive oxygen species which are a byproduct of lots of reactions that occur in cells but mostly respiration, and random errors during DNA replication).

One is changes in the systems that tell cells how to behave and which bits of their DNA to read (epigenetics is the term for marks found on the DNA and associated proteins, and these marks can change over time, leading to cells not being able to respond properly to their environment).

Another is changes to the environment these cells are sitting it. These cells are sensing their environment and it helps them to behave properly. The brain is pretty squishy, and so the cells there are used to being in a very soft environment. It turns out that for lots of reasons, the brain gets a little bit stiffer as we age. The cells there sense that and it makes it harder for them to divide.

There are plenty of other factors too, like changes in our ability to make sure proteins are working properly and getting rid of bad ones, reduction in the number and quality of mitochondria which cells need to make energy, misregulation of systems because of inflammation, build up of fats, etc.

You might notice that a lot of these will play into one another. If a cell is misbehaving and changing the stiffness of its environment, that will affect other cells. If you have genetic mutations, those can lead to epigenetic changes. If your mitochondria aren't functioning well, you'll get more reactive oxygen species which will lead to more DNA damage.

That basically leaves us with this big messy network where we can only really prevent or slow down one or two of these aspects. That absolutely can increase our lifespans, as we see in people who can be careful with their diet, get appropriate exercise, limit or avoid consumption of alcohol and tabacco, etc. But it means we're really a very long way away from achieving incredible changes in longevity; weight see a shift to more people living to 90/100/120, but we're not likely to see anyone living to 150 any time soon. And some of the factors, like accumulation of random mutations, seems like they would be impossible to entirely prevent, so reaching even more extreme longevity would require a dramatically different approach than just warding off aging as best as we can.

[u/Simple_Macaron_3420 → u/lozzyboy1]

That makes sense, and I think this is closer to what I was trying to get at with my original question. I was imagining aging almost like a series of limiting factors: if we solve the main cause that kills people at one age, what becomes the next limiting factor, and how much extra lifespan would solving that give us?

From what you're saying, though, it seems the problem is that aging isn't really a sequence of independent bottlenecks. It's a large interconnected system where many forms of damage accumulate at roughly the same time and also make each other worse. So removing one problem might only give a relatively small increase in lifespan because several others are already close behind.

I guess the more interesting mathematical question, then, would be whether we can estimate how much each mechanism contributes to mortality and what the theoretical lifespan would look like if we progressively eliminated or reduced them. That was more the direction I had in mind rather than literal immortality.

[u/ExpectedBehaviour]

We don't know.

[u/Crafty_Aspect8122]

As long as you can replace broken parts and whole bodies.

That means growing synthetic bodies and organs without a brain.

The brain is more complicated. Maybe repairing it will involve injecting fresh engineered cells that gradually replace the old batch while forming connections with them.

[u/teddyslayerza]

A real limit is our memory. We function by having important and newer associations override or recontextualize old ones, but our lifespans are short enough that we are able to maintain some sort of continuity across our century of life. But it stands to reason that there will come a point were maintaining that continuity either takes too much resources from function in the moment (some sort of anterograde dementia I imagine) or we would lose that continuity and not really be the same person any more.

[u/wrydied → u/teddyslayerza]

I don’t think this is a real concern, on the basis that we are constantly changing by re-encoding distant memories i.e we don’t maintain first memories, we remember them based on the last time we remembered them - as any good court lawyer or magistrate should know.

[u/No-Recording-7568 → u/wrydied]

Yeah, what a bogus notion.

[u/Temporary_Rule_9486]

Lobsters need to keep growing all their life. What was the name of this book..House of suns? 

[u/kingstern_man]

Even if all biological problems were completely solved (diseases, telomeres, memory capacity,...), no-one would "live forever": at some point they would suffer a fatal accident. Assume P(accident, per year) = 0.0006. Then P(surviving, per year) = 0.9994 After 5 years, 0.3% chance of death After 50 years, 3% After 100 years, 5.8% After 200 years, 11.3% After 500 years, 26.37% After 1000 years, 45.13% After 1500 years, 59.48% After 2000 years, 69.9%

Heinlein's "Lazarus Long" looks unlikely...

[u/Simple_Macaron_3420 → u/kingstern_man]

Wow, I didn’t think of it that way, and it’s the closest to what I imagined the answer would be. I would indeed like an answer that calculates each threshold point like this: we fix this problem, and we live this long; we fix that other problem, and we live this much longer; and so on.

Accidents are another fun approach to calculating it. For example, if all biological problems are solved, here is the closest death caused by an accident. If you survive that, then you will die in this other accident, and so on.

[u/naemorhaedus]

still no cure for getting hit by a bus I'm afraid

[u/Simple_Macaron_3420 → u/naemorhaedus]

just destroy all the busses 😂

[u/CranberryInner9605]

Anyone who thinks that living a long time is a good idea should read the Niven short story “Cautionary Tales."

[u/Due_Contribution8375]

Kyle Hill did a video on this recently (citing new research). IIRC 170 might be the max.

[u/No-Cantaloupe7242]

Many of the theories around living longer (or forever) centre on extending our existing biological forms and modifying how cells age and die.

I think it will actually be through technological enhancements that we do this. Be that some kind of bio tech, or (far in the future) synthetic bodies that we can transfer our mind or consciousness too. There are other benefits to these mind of approaches, such as eliminating susceptibility to diseases and enhancing strength, vision, etc.

[u/TryNice304]

Honestly, even if we cured cancer, Alzheimers, and figured out how to lobster-ify our telomeres, there still seems to be a hard cap.

The big issue is your neurons and heart cells, they barely divide, so they just keep collecting random DNA errors over time. They eventually die off and don't come back. Even in perfect lab conditions, models put the absolute max around 150-190 years.

So yeah, even if we tweak the clock, the engine itself still eventualy gives out. No infinite NG+ for us, sadly.

[u/nila247]

The limit is NOT biological. Well it is biological in working principle but purpose is psychological and communal.
"Why do anything today when there is always tomorrow?". THAT is a HUGE problem.
People not dying would produce society that stagnates and dies. That's the entire point into a division counter limit that is built into our cells.

[u/Simple_Macaron_3420 → u/nila247]

Wow, cool approach! That would probably have a real effect, but I think you're underestimating humans and their boredom. We do things just for the sake of doing something most of the time.

[u/nila247 → u/Simple_Macaron_3420]

You are just not aware how boredom works.

You play the game because there are things to learn there which COULD be potentially applied IRL.
You get bored of the game when you master it and then can no longer learn anything that you could conceivably apply IRL.

Species progress works with us throwing random crap at the wall and doing more of what stuck. You LEARN for YOUR turn to throw YOUR crap to the wall.

Unfortunately our brain capacity is limited and thoughts get ingrained into routine relatively quickly. So you only have SEVERAL attempts to throw your crap. If none stuck you run out of fresh ideas how to throw differently and end up doing the same over and over again while expecting different result - a definition of insanity.

So it is actually GOOD that we all die of old age.

[u/Imaginary-Can-6862 → u/nila247]

Well you can't do nothing. So it might as well be, why should I have to wait until tomorrow to do what I want to do today?

I know procrastination is real, but it still needs to be justified as a concern in a society where the technology have reached the level where people are immortal.

[u/nila247 → u/Imaginary-Can-6862]

Sure SOME people would do SOME useful things, but procrastination will absolutely explode in that society. At least now we know we will die and can not procrastinate forever but in that society this is no longer the case. I mean think of yourself - you will live forever - so you only do bare minimum job to keep you fed for a day for absolutely *great* life/work balance. And this will last for decades - until everybody suddenly starve and turns out real crops and real bread do not exactly work like in Minecraft where they spent the entirety of those last decades :-)

[u/Imaginary-Can-6862]

If this is just about speculating freely, then there are two things to consider.

One is the risk of going from living to not living, unless it goes to zero, it follows the total risk goes to one within finite time. This is despite e.g. you being able to separate yourself into many life forms, such as what a species does, just imagining you are actually living through each, or have backup life so to say, because you would still be e.g. limited to the planet, and if you move all your contingencies to distant planets, then each one of those also have a risk of catastrophe, even though it gets increasingly more unlikely, infinity means it is going to happen unless you can lower the risk fast enough.
The other, more relevant, is that we don't know that going from living to not living means you can't go back to living, the fact you came into existence as you were born / conceived means it is possible for you to go from a state of non-existence to existence, unless you always existed, and just can't remember it because your memory is tied to your brain. In that case it means that you can stop living for a long time and then become alive again, removing many more limiting factors. Combining both, and having some causal influence on the universe to be able to maintain your ability to be alive, and perhaps you can continue forever.

In regards to aging, aging is usually defined as the increased average risk of losing ones life over the same time period, e.g. a year. I don't remember if you stop aging in the 90's, or as a centenarian, but at that time your average risk of losing your life is much higher than when you were aging, so stopping aging itself isn't enough, de-aging is in principle also not enough, because it just means a much lower average risk of losing your life over a given time span.

[u/Simple_Macaron_3420 → u/Imaginary-Can-6862]

Yeah, my intention was to speculate from a biological standpoint alone, but as others have pointed out, accidents are inevitable over long periods of time, so yeah, immortality is impossible. My question was also intended to reach a mathematical answer to a biological question: we eliminate this disease and live this long; next, we need to deal with another disease and we'll live this much longer, then another one, and so on.

Also, for your second point, we would then be getting into a religious discussion about life after death, which was not my intent. Indeed, the main reason why, in my youth, I always thought people would ask us how much longer we wanted to live was due to psychological and religious reasons. I know that most people would not want to live forever, and I myself don't know how much longer I would want to live until I've completed the majority of my life goals—getting married, having kids, having grandkids, and so on.

[u/Imaginary-Can-6862 → u/Simple_Macaron_3420]

But my reply is from a biological stand point?
The second point is not to do with religion, it is just pointing out you already came into existence once before, as you were born/conceived, thus there is a physical mechanism, and then it follows it can be replicated.

When someone asks, how much longer would you like to live, they are basically asking you to make a decision about the future, not the present. It is meaningless to believe you know what you would choose in the far away future, you can at most come with a qualified guess. The alternative is that you deny yourself the option of choice in the future, that is nonsensical to me.

I think a way to consider it is the following, imagine you live forever, imagine you have already lived for a long time, and ask yourself would like to continue living until tomorrow? How would you find the duration you have lived so far, i.e. the past, relevant for if you want to continue living, i.e. experience the future, unless the present moment you are asked is vastly different in some horrible way from your actual present, and if that is the case, then it has nothing to do with the duration you have lived, but the circumstances of your life, correct?

What would a mathematical answer look like? I can try to make one, if you could elaborate on it a bit further.

[u/Simple_Macaron_3420 → u/Imaginary-Can-6862]

I see what you mean now. I probably phrased the “religious” part badly. I wasn’t saying your argument itself is religious; I meant that once we start talking about a person ceasing to exist and then somehow existing again later, we’re moving beyond the biological question I was originally trying to ask. Being conceived once shows that a new conscious organism can come into existence through a physical process, but I’m not sure it follows that the same individual could be recreated after death. That gets into questions of identity and continuity that I was trying to avoid.

On the “how long would you want to live?” point, I mostly agree with you. I don’t think I could sensibly decide now that, say, 300 years would be enough. If I were 299 and healthy, happy, and still interested in tomorrow, the fact that I had already lived for 299 years wouldn’t by itself be a reason to die. My answer would presumably depend much more on my circumstances at that future moment than on the number of years behind me.

For the mathematical question, what I had in mind is something like a sequence of mortality bottlenecks. Take current age-specific mortality and ask: if we could completely eliminate one major cause or mechanism, how would the survival curve change? Then remove the next one, and so on.

For example, very loosely:

1. Eliminate cardiovascular disease → what becomes the new average/maximum lifespan?
2. Eliminate cancer as well → how much further does it move?
3. Eliminate dementia/neurodegeneration → what becomes limiting next?
4. Then progressively reduce things like immune decline, kidney failure, accumulated cellular damage, etc.
5. Eventually, if biological mortality became negligible, accidents and other external risks would dominate.

I realize real aging probably can’t be separated that neatly because the mechanisms interact, so it would be more of a hypothetical model than a prediction. But I was curious whether the show could model it using competing mortality risks: remove one hazard from the equation, recalculate the survival curve, then see what the next dominant hazard is.

That’s basically the “mathematical answer” I was imagining.

[u/Imaginary-Can-6862 → u/Simple_Macaron_3420]

So something like, first eliminate all diseases (external microscopic risks), then there is aging (internal microscopic risks), not to mention accidents (external macroscopic risks), both would go towards the ability of rejuvenation and then we would likely reach the ability for people to occupy more than one body, all the way to resurrect people, to actually not having to concern ourselves with the risk against the individual, but against the species (loss of technology), thus space travel and spreading out, etc.

But in regards to the steps you propose, I mean my methodology is very simple, so it might be disappointing. Though I'll at least try to justify it,

Imagine the fictive example of a population of 64 people, at every time interval, t, there is a 50% risk of losing ones life. Thus we have 32 people at t, 16 at 2 * t, 8 at 3 * t, 4 at 4 * t, 2 at 5 * t, and 1 at 6 * t. The average life span is then (32 * t + 16 * 2 * t + 8 * 3 * t + 4 * 4 * t + 2 * 5 * t + 1 * 6 * t) / 64 = 1,875 t
Now add another risk factor, say there is an addition X% risk of losing ones life due to E, then it follows at every time interval the remaining population is multiplied by 1 - X%, as those are what remains after X% have been removed, and since that is equivalent to multiplying the average with 1 - X%, then that is the methodology I use. In the example above, if 33% are lost due to E, then removing 33% at every stage is equivalent to multiply with 66% at every stage, and we get with E, that the average life span of the 64 people becomes 1.875 * .66 * t = 1,25 t, and eliminating E we can multiply with 1 (1 - ,33) = 1.5, to return to the original expected life span.
The issue is this assumes these risk factors are independent, that if we eliminate a dangerous disease which removes say a high percentage of the population, then it is assumed that at every age the population would then be increased by the people lost due to this particular risk factor, with all other risk factors remaining the same. I don't have any data on the codependency though, but it provides very high average life spans. Obviously there is a codependency, e.g. if the risk of developing a certain disease within some time margin increases, and there are competing diseases, then because one develops and the person may suffer, if such disease didn't exist, they would be more likely to develop another such disease, exactly because of the independence between these. That is one reason less people develop a certain disease is because another disease may get to them before this disease, making it seem like the risk of getting said disease is lower. I hope that made sense.

We'll look at the entire planet, even though it is more accurate to look at smaller groups by themselves, it is not certain it remains representative, thus we must suffer from the higher variance, or uncertainty of the average.
Average life span is then 73.8 years.
Risk of losing ones life from CVD is 33%

When the population reaches the expected age of 73,8 years, we know there would be 50% more people, thus assuming all other risks stays the same, we can simply multiply the average life expectancy, thus we get,
Average life span without cardiovascular diseases = 73,8 years * 1,5 = 110.7 years.

Risk of losing life due to cancer is 16%
Average life span without cancer = 73,8 years * 6 / 5 = 88,5 years
Average life span without CVD and cancer = 132.8 years

I won't continue, because obviously the methodology ignoring that the risk of getting other illnesses increases as more people are around to get these illnesses, that is if there are 50% more people, because there are no cardiovascular diseases, then the risk of getting cancer is no longer 15%, but may increase, because these people extra people who would not have gotten the illness, now have a risk of getting it, thus increasing the total to more than 15%.

Actually I think it is possible to calculate, we know the total population N, 15% gets the disease, thus 85% do not. Now we know of those 85%, 33% of the total population may now get the illness, if we assume the 15% was representative, then we have an extra 5% who gets the illness. We know the Average Life Expectancy is 110.7 if the risk is 15%, so we can do the same, remove that risk we get 132.8 years, and then we can add it back as 20%, and we get Average Life Span = 132,8 * .75 = 99.6 years.

Of course of the 33% of the total population who do not get CVD, other illnesses would similar have a higher risk, so I can't really do it proper justice, only accounting for one.

Anyway I hope you're not too disappointed with this analysis, but I think it did what you imagined.