On values: while I share your desire that we could live arbitrary old, we should also take care of the unintended consequences. The one that always come to mind is: how will we spare space for the youths? I do think satisfying solutions exists (for example, elders past 150 could be require to take increasingly long vampire-style naps), but I encourage you to think and write your own solution on how to make ultra-high longevity sustainable at the societal level, as it’ll almost always be the core objection of your most motivated opponents.
On hard reality is a bitch: the biologist in me is very confident that it’s terribly misleading to think biological ageing as a simple accumulation of damages. I suspect you’re making a categorical mistake by confusing what you wish to achieve (that one day we will consider ageing as unimportant as scratching a knee cap) with how simple animal physiology accept to be.
A few paradigmatic counter-points:
Cancer is not just damaged cells: they are subjected to natural selection, which makes fighting cancer look more like trench warefare than changing broken tiles.
In a close vein, we should expect some virus (some of which might be dormant in our own genome, or within the genome of our own microbiote) or bacteria to have learned when the host is old enough it’s time to strike for your own fitness purposes (I suspect that’s the main reason why transfusing young blood benefits older organisms -by fooling the wannabe scavengers into believing you would fight back as hard as if you’d risk missing your most productive breeding years)
CRPS is proof that a minor tissue damage can lead to a disease that is not only far worse, but also persisting long after the initial damage is fully repaired. In the same vein, most chronic back pain persist without any persisting evidence for tissue damage, and you might want to count PTSD as well.
Progeria and menopause strongly suggest that aging is, at least partially, under genetic control.
The one that always come to mind is: how will we spare space for the youths?
I’m unusually chill when it comes to population, both over and under. I’m not enormously concerned by how many people there are, I’m more concerned by how healthy the existing people are, and how healthy the environment is, both of which are mostly orthogonal to population and depend primarily on technological development. It’s important to note that fertility rates are generally declining worldwide, seemingly in tandem with economic development. The most economically developed countries generally have below-replacement fertility rates, and are facing depopulation plus highly inverted population pyramids (high ratio of sick, dependent, aged people) if something doesn’t change. In places where fertility is below two children per woman, you could abolish death completely and population will plateau, since each generation produces fewer children than the one before, so you get a geometric series with r < 1. Thus, the only study I’m aware of that analyses the demographic consequences of rejuvenation therapies predicts only slow and limited population growth (at least in Sweden).
Of course, it all depends how fertility changes. Ending reproductive senescence could allow people to postpone childbirth even further than they already do, lowering fertility rates further, or it could lead to people having more children throughout their greatly extended lifetimes. I suspect the former will occur, but time will tell.
the biologist in me is very confident that it’s terribly misleading to think biological ageing as a simple accumulation of damages
Oh, I hope I didn’t give the impression that this was simple. One of my core points is that ageing cannot be reduced to any single target for intervention, there is no way around the fact that ageing is many-faceted and will require complex combination therapies to address. I only assert that there will be some combination of damage which, if eliminated, will elicit healthy life extension, and that we have some well educated guesses as to what those are and how to go about fixing them, and that doing so can only be good for people even if damage identified by SENS platform is not in fact comprehensive.
Counter-counter-points:
Yes, cancer is hard and I glossed over it. Partly it will be mitigated by immune system rejuvenation, since immune surveillance plays a huge role in cancer suppression. Dealing with mitochondrial dysfunction should also reduce cancer incidence, by lowing the amount of free-radical assault on DNA. Aside from that though, there are exciting things happening in actual cancer therapy: cancer immunotherapy (works very well in blood cancers, might scale to solid cancers), THIO by MAIA Biotechnology (rapidly kills cells that express high levels of telomerase, which most cancers do by necessity), Lou Hawthorne’s NaNots (can safely remove stuff from the blood, can be used to soak up the soluble immune system inhibitors that tumours have to use to protect themselves from the immune system, and finally, Michael Levin’s lab have managed to suppress cancers using ion channel drugs, along with opening a whole new perspective on what cancer fundamentally is.
The effects rejuvenating effects of parabiosis are due to either good things in the young blood, or dilution / removal of bad things (e.g. inflammatory signalling molecules) in the old blood. The debate continues, but I believe consensus is leaning towards the latter, since you can achieve similar results just by diluting the blood with saline-albumin [1,2].
Function follows form. If there are diseases that aren’t associated with any obvious damage, then that only means we’ve yet to identify what the damage is. Machines do what they do because their structure; if they malfunction, then there must some change somewhere in the structure that causes it, and whatever that change is, we call it damage. Remember that damage is defined very broadly, it doesn’t have to be what you’d think of as “wear-and-tear” necessarily—it could be something like over-sensitisation of a particular type of neuron in the case of CRPS, for example.
Progeria (assuming you mean Hutchinson-Gilford syndrome) is a mutation in a critical nuclear envelope protein which causes rapid and widespread damage of many forms, since it’s such a critical component that’s defective. It’s thought of as “premature ageing” since its symptoms resemble accelerated normal ageing, probably because “widespread damage of many forms” is what normal ageing is, but that doesn’t mean that the damage involved in progeria is the same as in normal ageing (though there’s probably some overlap). As for menopause, it’s kind of a moot point to me whether a change is “under genetic control” (difficult to define since everything is ultimately determined by genes anyway) or not. Thymic involution appears to be a programmed developmental change, but we still call it damage, because it causes a loss of function (inability to make new naive T-cells). We don’t much care how damage happens, only how to reverse it.
In places where fertility is below two children per woman, you could abolish death completely and population will plateau
Why would fertility per woman stay the same when childbearing lifespan is increased? It seems more likely to me that fertility per woman per year would stay the same—have a kid or two, then a few decades doing other things, then another kid or two and so on. And this leads to exponential growth (as long as fertility/woman/year > 0).
Is that really conter counter? Levin’s idea on long range communication fits well with the ideas of cancer as learning system, even better than natural selection alone. Also, the impact of diluting blood seems 100% compatible with the idea that it’s diluting an ageing marker (indeed inflammatory molecules are excellent candidates).
If there are diseases that aren’t associated with any obvious damage, then that only means we’ve yet to identify what the damage is
we still call it damage, because it causes a loss of function
These definitions are imho too forgiving.: if we define damage as loss of health, then sure « removing damage » will tautologically cause good health. If we define damage as material defects, which I think is closer to your original intent, then maladaptative memories (of the affective system in PTSD, of the pain system in CRPS, of the immune system….) can cause a loss of function without a lasting role for material damages (beside killing oneself when it’s no longer possible to cope with this level of pain|suffering)
If we define damage as material defects, which I think is closer to your original intent, then maladaptative memories (of the affective system in PTSD, of the pain system in CRPS, of the immune system….) can cause a loss of function without a lasting role for material damages
“Material”? I don’t think it’s useful to distinguish between material and immaterial change, the point is that the change is maladaptive. If your hard drive gets corrupted preventing your computer from booting then we still call that damage, even though it seems less material than, say, shooting the PSU. And ultimately, data and code are material anyway, whether they’re represented by patterns of magnetic polarisation or changes to neuronal sensitivity or connectivity or whatever.
Very good points. The obvious solutions are either really low birth rates and/or aggressive expansion into space. Both of which are hard.
In a certain sense it’s correct to say that resetting the whole body to a 25 year olds level would fix most health problems. The problem with this is that it’s also the solution to fixing a broken vase. Biology has a very nasty habit of turning out to be even more complicated than you expected when you start digging deeper. Cleaning up doesn’t have to suffice—there are various intra- and extracellular (i.e. hormones) interactions, cascades and what not which would also have to be set appropriately.
The biologist in me would also like to point out the existence of zombie genes, which start expressing themselves after death—more as a curiosity than a specific point—animal physiology is fascinating.
Suppose a future technological trick allows our civilisation to magically size and control anything material within a spheric bubble growing at light speed: that means what we own would grow as a polynomial (2 or 3, depending on your TOE). But polynomial growth is not enough to cope with any fixed grow rate of the population (that’s exponential), so that’s why I think amortals should play on time to make space. In permutation city, Greg Egan imagine the uploaded could play with their refreshing speed. In the context of biological immortality, taking long naps could serve the same purpose.
Always glad to see Greg Egan referenced. The important thing to me is that although population growth could be exponential (for the reasons cousin_it gave), it’s going to be very slow relative to the rate of technological progress. Unless fertility rises significantly, it’s likely to be hundreds of years before population would grow by 10x, by which point we’re well into Greg Egan territory and all bets are off anyway. So population could be a concern, but we’ll have plenty of time to address it via methods that don’t involve literally everyone dying.
On second thought, strong upvote for this answer because I think it’s key to pinpoint our divergence.
You think that we will likely be well into Greg Egan territory in a few hundred years, whereas new tools in biology are so fantastic we are a few decades to, yes immortality, but I guess you see that as a direct consequence of reaching biological universality (when we can basically at will make cells do whatever one cell can do).
To me (and, in a sense, echoing Vladimir_Nesov´s comment above) that’s the contrary: not only I expect new biological limitations to show up nearly as fast as we solve old problems (like decoding the human genome was fantastic, and fruitful, but not as fruitful as I was naively thinking at the time), but I also fully expect we will taste Greg Egan territory several decades before we will fully master our own biology.
Late late late disclaimer: I’m toying with the idea of starting a series of post called Road to amortality, so you should expect me to be biased and stubbornly attached to my ideas. 😉
To fight the latter, here’s one result that would move me toward your position: if we can print or grow any complex organ within the next decade. Do you accept this criteria as fair and to the point? Would you mind thinking of some results that would make you strongly update toward my position?
Naps would handle the amount of people walking around, but would probably require some novel approaches to ownership to work properly. Or synchronization of when people wake up? With the current norms, you’d end up with empty cities, because a large fraction of the inhabitants would be asleep at each given moment. Though magically sizing stuff would also handle that issue.
After reflexion I still don’t get your point, e.g. what problems intermittent naps would make us need new approach to ownership. Say we the people agree for sustainability purpose to set a fix number A as the number of people allowed & required to be awake, and P is the total number of people, sleeping or awake. Then everyone would have a right to be awake A/P of the years, or A/P decades within each millennia, and from that we might want to trade synchronisation with Star War MCXIV release for synchronisation with Harry upcoming new biography, the way Smith intended capitalism. What am I missing?
Assume you have a population of 1000 billion people on earth (what with the hibernation tech), with most of them sleeping at any given time, so that you only have 10 billion awake. If everyone has their own apartment/house then at any given time, only 1% of the houses will be in use. This in itself is fine, as people can simply synchronize when they wake up to have empty/full neighborhoods. But it would also require either having 100x more infrastructure to handle the larger cities (or paving over the world, or more exotic solutions), giving everyone a lot less living room (e.g. pod skyscrapers) or having shared accommodations (like hotels or shared bedrooms).
My main point is that the current approach, where a house with a large garden is the default to strive for, would be totally untenable. Which in turn would require a lot of cultural changes (people tend to like having lots of room for themselves). This by no means invalidates the idea of napping, it’s just something that would have to be handled.
I’m guessing compounded interest could also be troublesome in the long run, e.g. you start a savings account now, and someone else starts in a million years—that would introduce some scary inequality. For the same reason that the older the vampire, the more powerful.
Ok, thanks for clarifying (I misunderstood « approaches » as implying new economical system). Yes, that scenario would need us to change some of our habits, for example we could share home with P/A family member, or rent it while sleeping.
compounded interest could also be troublesome in the long run
Interesting thought. On the other hand, the more sleepers, the more capital, the lower the interest rate. And what kind of bank could we trust for one million years?
You may well turn out to be correct—biology is indeed fiendishly complex and still very poorly understood, and it may turn out that clearing the damage types identified by the SENS platform is insufficient for comprehensive rejuvenation. However, I’ve tried to separate that particular claim from a different, more defensible, more immediately relevant one: that damage repair should become our main approach to medical research in a world where infectious disease is largely conquered, and most suffering is due to (mostly age related) chronic illnesses. Most bodily disorders these days are caused not by infection by an external pathogen, but by damage to the body itself, most of which is self-inflected by ordinary metabolic processes. Yet for some reason, we continue to treat the (often arbitrarily defined) diseases themselves, as though they were infectious diseases, instead of even trying to repair the damage that causes them. This must change, and it is changing. To me, damage repair is a first and foremost a new, fundamentally different approach to medicine, one that emphasizes fixing things that are obviously broken, which I expect to work much better than the old paradigm of treating diseases separately. The whole “ageing” thing is almost secondary to me. We’ve literally not been fixing people’s bodies this entire time, and now people are finally trying to fix a bunch of obviously broken things, that’s why I’m excited.
To me, damage repair is a first and foremost a new, fundamentally different approach to medicine, one that emphasizes fixing things that are obviously broken, which I expect to work much better than the old paradigm of treating diseases separately. The whole “ageing” thing is almost secondary to me. We’ve literally not been fixing people’s bodies this entire time, and now people are finally trying to fix a bunch of obviously broken things, that’s why I’m excited.
I like the parts of the post I’ve read so far, and I’m just making a local argument to this specific bit.
People have been fixing people’s bodies insofar as they can, since the dawn of medicine. They’ve been setting bones, stitching wounds, treating or preventing inflammation and autoimmune reactions, and more recently, destroying or removing cancer and transplanting organs.
What unites SENS interventions is that they require sophisticated cellular and subcellular therapies that depend on the stack of biomedical technologies we’ve produced at an accelerating pace over the last century. Cellular senescence was discovered in vitro a little over 60 years ago, and as recently as 1996, a Berkeley cancer biologist was still writing in Cell that “a limited number of in vivo experiments… strongly suggest that cellular senescence is not an artifact of culture,” i.e. that it takes place in the body, not just in a dish, though the potential mechanistic links between senescence as a tumor suppression mechanism and driver of aging were already well-known. We only sequenced the human genome in 2003, and Crispr-CAS9 has only been around since 2012.
Point being that we’ve been trying to fix people’s bodies for millennia, but we’ve only had the scientific knowledge and bioengineering technology that might potentially allow us to treat the cellular and subcellular precursors of homeostatic breakdown (“aging”) for a matter of years.
Yes we’ve always been trying to fix damage—anything that restores function must fix damage somehow—but it’s a matter of what we consider to be damage, i.e. “bad stuff that we should try to fix because it would restore function”. Historically we’ve focused on trauma, infection and cancer, and although we’ve known about age-related changes like lipofuscin accumulation for a long time, it’s only recently that we started thinking of them as potential targets. Gerontology has historically been a field of basic science, with few gerontologists willing to venture that we could even in principle do something about age-related changes until very recently. They were too afraid to challenge the deeply held notion that ageing is normal, natural and fundamentally immutable. I’m not without sympathy though—anyone who had made that claim would have been attacked and likely would have lost their livelihood—Aubrey de Grey was only able to do it because he was financially independent.
If you look at things like atherosclerosis and AMD, both of which have long been known to be driven by the accumulation of toxic metabolites, I think we could and should have started working on the root causes of these diseases much earlier than we did. Sure, we’re only now figuring out how to remove 7KC and A2E, but that’s because we only just started working on it! Likewise, we’ve known about thymic involution for a long time and it’s always been clear that it damages your immune system in the long run, so why is it that only Greg Fahy is working on fixing it, and why does he get so little funding that his trials have to be funded by their own participants? We declared war on cancer long ago, when our models and tools were still hopelessly crude, and because of that we are further advanced now than we would have been otherwise.
Point taken that this is all extremely difficult and ambitious, and it’s not entirely unreasonable that researchers have been intimidated by that. Rejuvenation is indeed highly dependent on very recent technological breakthroughs, and those new capabilities are a huge part of why this shift is occurring. In my defense, there is a bit where I say
I don’t mean to imply that prior researchers had been stupid here; humans don’t come equipped with enzymes capable of degrading A2E so it wasn’t exactly obvious how to get rid of it.
Perhaps I could have stressed that more. To whatever extent there is blame, I place it more on grant committees than on medical researchers. The stuff SENS works on is all high-risk high-reward, which public purse-holders and investors are both cagey about—that’s why it all has to be philanthropically funded. For example, the idea to copy mitochondrial DNA into the nucleus where it is safer (which I ignored completely in the post) has been around for a long time, but SENS had to work on it because no one else would.
Anyway, I don’t want to fixate on whose fault things were. The point is that for whatever reason, we were pursuing a broken paradigm of “one disease one target one drug”, which was never going to work because the diseases were not naturally separable things and their root causes mostly lay in fundamental age-related changes, which we are now beginning to target, and it seems likely to work.
Agreed, I like this elaboration. As I see it, the argument really is that we’ve been neglecting preventative medicine in favor of treating disease after it has become symptomatic. This is a familiar critique that normal doctors and laypeople already subscribe to, and showing that anti-aging medicine is really just another familiar form of preventative medicine (which we have historically neglected) will make more immediate sense than claiming that “we haven’t been fixing people’s bodies” which is only true in the specific sense you just articulated.
Along with that is emphasizing that it’s normal and natural to use preventative medicine. You brush your teeth, you try to eat a good diet and get enough sleep and exercise, you might stake preventative statins or blood thinners or get LASEK. If you’ll do all these things to maintain your health, then why not take low-dose rapamycin? It’s really going to be about normalizing the use of pill-form preventatives at an earlier age, and breaking the association between pills and “being sick.” Instead, it’s about creating an association between pills and “maintaining health.”
It’s both prevention and cure—prevent disease by reversing damage before it gets bad enough to cause problems, but if you already have a chronic disease, then reversing the damage that causes it will be the only way to cure it (though prevention is better of course).
I agree the preventative medicine angle is a good one that people will buy easily, but you can make the same argument against it—that we’ve always been trying to prevent disease just as we’ve always been trying to fix damage.
It’s important to note that statins, blood thinners and rapamycin are not damage repair—they’re not useless, but I think damage repair will make them obsolete. These approaches focus on slowing the buildup of damage rather than reversing damage that’s already there. The problem is that a) this tries to modify human metabolism to “run more cleanly”, which is super difficult and prone to unforeseen consequences and b) you have to take these medicines every day, which makes it all the more dangerous. Statins are well known to have side effects, and rapamycin is an immunosuppressant, which unsurprisingly has a lot of side effects too. You don’t want to take this stuff every day.
The reason people associate things like statins with “being sick” is that they don’t actually make you less sick, they just slow the progression of a disease while causing side effects. Damage repair is far less prone to side effects because it targets stuff that’s definitely not supposed to be there instead of trying to change the way the body works. You won’t get side effects from removing atheromatous plaques (so long as that’s all the treatment does do), but you do get side effects from mucking around with liver chemistry. And because ageing damage accumulates so slowly, you’ll only have to take these therapies every 10 years or so (eventually, once they’re mature). And of course, because it reverses damage instead of merely slowing it, you’ll actually feel, look and be healthier and fitter after the treatment. That’s why I say it’s a new kind of medicine—the public are absolutely not used to medicine that makes them feel younger after they take it.
That’s a reasonable point of view. I don’t think we should be certain that the effects of rapamycin at high doses will be reflective of its effects at low doses, which is why we need to test it. This era is all about precision medicine, figuring out how to control dosing, release, and specific delivery in the context of much better knowledge of how these drugs affect the body to cut side effects and enhance benefit.
The heuristic of leaning toward occasional damage repair by engineered interventions rather than continuous damage slowdowns by manipulating evolved biochemistry makes sense, but so does the heuristic of focusing on an available tool that we have extensive data works pre-clinically right now. I think the “don’t mess with evolution” heuristic is oversubscribed for antagonistic pleiotropy and declining selection pressure with age reasons when it comes to anti-aging medicine.
All the same, I expect that over time we’ll come up with a wide range of both preventative and damage reversal interventions, perhaps along SENS lines. But in that context, a damage-slowing drug (perhaps rapamycin) that might reduce the frequency of the need for damage reversal therapies will be highly valuable, and particularly because it may well be the cheapest and most accessible option to get started, especially in countries that don’t yet have fully developed medical systems..
On values: while I share your desire that we could live arbitrary old, we should also take care of the unintended consequences. The one that always come to mind is: how will we spare space for the youths? I do think satisfying solutions exists (for example, elders past 150 could be require to take increasingly long vampire-style naps), but I encourage you to think and write your own solution on how to make ultra-high longevity sustainable at the societal level, as it’ll almost always be the core objection of your most motivated opponents.
On hard reality is a bitch: the biologist in me is very confident that it’s terribly misleading to think biological ageing as a simple accumulation of damages. I suspect you’re making a categorical mistake by confusing what you wish to achieve (that one day we will consider ageing as unimportant as scratching a knee cap) with how simple animal physiology accept to be.
A few paradigmatic counter-points:
Cancer is not just damaged cells: they are subjected to natural selection, which makes fighting cancer look more like trench warefare than changing broken tiles.
In a close vein, we should expect some virus (some of which might be dormant in our own genome, or within the genome of our own microbiote) or bacteria to have learned when the host is old enough it’s time to strike for your own fitness purposes (I suspect that’s the main reason why transfusing young blood benefits older organisms -by fooling the wannabe scavengers into believing you would fight back as hard as if you’d risk missing your most productive breeding years)
CRPS is proof that a minor tissue damage can lead to a disease that is not only far worse, but also persisting long after the initial damage is fully repaired. In the same vein, most chronic back pain persist without any persisting evidence for tissue damage, and you might want to count PTSD as well.
Progeria and menopause strongly suggest that aging is, at least partially, under genetic control.
I’m unusually chill when it comes to population, both over and under. I’m not enormously concerned by how many people there are, I’m more concerned by how healthy the existing people are, and how healthy the environment is, both of which are mostly orthogonal to population and depend primarily on technological development. It’s important to note that fertility rates are generally declining worldwide, seemingly in tandem with economic development. The most economically developed countries generally have below-replacement fertility rates, and are facing depopulation plus highly inverted population pyramids (high ratio of sick, dependent, aged people) if something doesn’t change. In places where fertility is below two children per woman, you could abolish death completely and population will plateau, since each generation produces fewer children than the one before, so you get a geometric series with r < 1. Thus, the only study I’m aware of that analyses the demographic consequences of rejuvenation therapies predicts only slow and limited population growth (at least in Sweden).
Of course, it all depends how fertility changes. Ending reproductive senescence could allow people to postpone childbirth even further than they already do, lowering fertility rates further, or it could lead to people having more children throughout their greatly extended lifetimes. I suspect the former will occur, but time will tell.
Oh, I hope I didn’t give the impression that this was simple. One of my core points is that ageing cannot be reduced to any single target for intervention, there is no way around the fact that ageing is many-faceted and will require complex combination therapies to address. I only assert that there will be some combination of damage which, if eliminated, will elicit healthy life extension, and that we have some well educated guesses as to what those are and how to go about fixing them, and that doing so can only be good for people even if damage identified by SENS platform is not in fact comprehensive.
Counter-counter-points:
Yes, cancer is hard and I glossed over it. Partly it will be mitigated by immune system rejuvenation, since immune surveillance plays a huge role in cancer suppression. Dealing with mitochondrial dysfunction should also reduce cancer incidence, by lowing the amount of free-radical assault on DNA. Aside from that though, there are exciting things happening in actual cancer therapy: cancer immunotherapy (works very well in blood cancers, might scale to solid cancers), THIO by MAIA Biotechnology (rapidly kills cells that express high levels of telomerase, which most cancers do by necessity), Lou Hawthorne’s NaNots (can safely remove stuff from the blood, can be used to soak up the soluble immune system inhibitors that tumours have to use to protect themselves from the immune system, and finally, Michael Levin’s lab have managed to suppress cancers using ion channel drugs, along with opening a whole new perspective on what cancer fundamentally is.
The effects rejuvenating effects of parabiosis are due to either good things in the young blood, or dilution / removal of bad things (e.g. inflammatory signalling molecules) in the old blood. The debate continues, but I believe consensus is leaning towards the latter, since you can achieve similar results just by diluting the blood with saline-albumin [1,2].
Function follows form. If there are diseases that aren’t associated with any obvious damage, then that only means we’ve yet to identify what the damage is. Machines do what they do because their structure; if they malfunction, then there must some change somewhere in the structure that causes it, and whatever that change is, we call it damage. Remember that damage is defined very broadly, it doesn’t have to be what you’d think of as “wear-and-tear” necessarily—it could be something like over-sensitisation of a particular type of neuron in the case of CRPS, for example.
Progeria (assuming you mean Hutchinson-Gilford syndrome) is a mutation in a critical nuclear envelope protein which causes rapid and widespread damage of many forms, since it’s such a critical component that’s defective. It’s thought of as “premature ageing” since its symptoms resemble accelerated normal ageing, probably because “widespread damage of many forms” is what normal ageing is, but that doesn’t mean that the damage involved in progeria is the same as in normal ageing (though there’s probably some overlap). As for menopause, it’s kind of a moot point to me whether a change is “under genetic control” (difficult to define since everything is ultimately determined by genes anyway) or not. Thymic involution appears to be a programmed developmental change, but we still call it damage, because it causes a loss of function (inability to make new naive T-cells). We don’t much care how damage happens, only how to reverse it.
Why would fertility per woman stay the same when childbearing lifespan is increased? It seems more likely to me that fertility per woman per year would stay the same—have a kid or two, then a few decades doing other things, then another kid or two and so on. And this leads to exponential growth (as long as fertility/woman/year > 0).
Is that really conter counter? Levin’s idea on long range communication fits well with the ideas of cancer as learning system, even better than natural selection alone. Also, the impact of diluting blood seems 100% compatible with the idea that it’s diluting an ageing marker (indeed inflammatory molecules are excellent candidates).
These definitions are imho too forgiving.: if we define damage as loss of health, then sure « removing damage » will tautologically cause good health. If we define damage as material defects, which I think is closer to your original intent, then maladaptative memories (of the affective system in PTSD, of the pain system in CRPS, of the immune system….) can cause a loss of function without a lasting role for material damages (beside killing oneself when it’s no longer possible to cope with this level of pain|suffering)
“Material”? I don’t think it’s useful to distinguish between material and immaterial change, the point is that the change is maladaptive. If your hard drive gets corrupted preventing your computer from booting then we still call that damage, even though it seems less material than, say, shooting the PSU. And ultimately, data and code are material anyway, whether they’re represented by patterns of magnetic polarisation or changes to neuronal sensitivity or connectivity or whatever.
Very good points. The obvious solutions are either really low birth rates and/or aggressive expansion into space. Both of which are hard.
In a certain sense it’s correct to say that resetting the whole body to a 25 year olds level would fix most health problems. The problem with this is that it’s also the solution to fixing a broken vase. Biology has a very nasty habit of turning out to be even more complicated than you expected when you start digging deeper. Cleaning up doesn’t have to suffice—there are various intra- and extracellular (i.e. hormones) interactions, cascades and what not which would also have to be set appropriately.
The biologist in me would also like to point out the existence of zombie genes, which start expressing themselves after death—more as a curiosity than a specific point—animal physiology is fascinating.
Suppose a future technological trick allows our civilisation to magically size and control anything material within a spheric bubble growing at light speed: that means what we own would grow as a polynomial (2 or 3, depending on your TOE). But polynomial growth is not enough to cope with any fixed grow rate of the population (that’s exponential), so that’s why I think amortals should play on time to make space. In permutation city, Greg Egan imagine the uploaded could play with their refreshing speed. In the context of biological immortality, taking long naps could serve the same purpose.
Always glad to see Greg Egan referenced. The important thing to me is that although population growth could be exponential (for the reasons cousin_it gave), it’s going to be very slow relative to the rate of technological progress. Unless fertility rises significantly, it’s likely to be hundreds of years before population would grow by 10x, by which point we’re well into Greg Egan territory and all bets are off anyway. So population could be a concern, but we’ll have plenty of time to address it via methods that don’t involve literally everyone dying.
On second thought, strong upvote for this answer because I think it’s key to pinpoint our divergence.
You think that we will likely be well into Greg Egan territory in a few hundred years, whereas new tools in biology are so fantastic we are a few decades to, yes immortality, but I guess you see that as a direct consequence of reaching biological universality (when we can basically at will make cells do whatever one cell can do).
To me (and, in a sense, echoing Vladimir_Nesov´s comment above) that’s the contrary: not only I expect new biological limitations to show up nearly as fast as we solve old problems (like decoding the human genome was fantastic, and fruitful, but not as fruitful as I was naively thinking at the time), but I also fully expect we will taste Greg Egan territory several decades before we will fully master our own biology.
Late late late disclaimer: I’m toying with the idea of starting a series of post called Road to amortality, so you should expect me to be biased and stubbornly attached to my ideas. 😉
To fight the latter, here’s one result that would move me toward your position: if we can print or grow any complex organ within the next decade. Do you accept this criteria as fair and to the point? Would you mind thinking of some results that would make you strongly update toward my position?
Naps would handle the amount of people walking around, but would probably require some novel approaches to ownership to work properly. Or synchronization of when people wake up? With the current norms, you’d end up with empty cities, because a large fraction of the inhabitants would be asleep at each given moment. Though magically sizing stuff would also handle that issue.
After reflexion I still don’t get your point, e.g. what problems intermittent naps would make us need new approach to ownership. Say we the people agree for sustainability purpose to set a fix number A as the number of people allowed & required to be awake, and P is the total number of people, sleeping or awake. Then everyone would have a right to be awake A/P of the years, or A/P decades within each millennia, and from that we might want to trade synchronisation with Star War MCXIV release for synchronisation with Harry upcoming new biography, the way Smith intended capitalism. What am I missing?
Assume you have a population of 1000 billion people on earth (what with the hibernation tech), with most of them sleeping at any given time, so that you only have 10 billion awake. If everyone has their own apartment/house then at any given time, only 1% of the houses will be in use. This in itself is fine, as people can simply synchronize when they wake up to have empty/full neighborhoods. But it would also require either having 100x more infrastructure to handle the larger cities (or paving over the world, or more exotic solutions), giving everyone a lot less living room (e.g. pod skyscrapers) or having shared accommodations (like hotels or shared bedrooms).
My main point is that the current approach, where a house with a large garden is the default to strive for, would be totally untenable. Which in turn would require a lot of cultural changes (people tend to like having lots of room for themselves). This by no means invalidates the idea of napping, it’s just something that would have to be handled.
I’m guessing compounded interest could also be troublesome in the long run, e.g. you start a savings account now, and someone else starts in a million years—that would introduce some scary inequality. For the same reason that the older the vampire, the more powerful.
Ok, thanks for clarifying (I misunderstood « approaches » as implying new economical system). Yes, that scenario would need us to change some of our habits, for example we could share home with P/A family member, or rent it while sleeping.
Interesting thought. On the other hand, the more sleepers, the more capital, the lower the interest rate. And what kind of bank could we trust for one million years?
You may well turn out to be correct—biology is indeed fiendishly complex and still very poorly understood, and it may turn out that clearing the damage types identified by the SENS platform is insufficient for comprehensive rejuvenation. However, I’ve tried to separate that particular claim from a different, more defensible, more immediately relevant one: that damage repair should become our main approach to medical research in a world where infectious disease is largely conquered, and most suffering is due to (mostly age related) chronic illnesses. Most bodily disorders these days are caused not by infection by an external pathogen, but by damage to the body itself, most of which is self-inflected by ordinary metabolic processes. Yet for some reason, we continue to treat the (often arbitrarily defined) diseases themselves, as though they were infectious diseases, instead of even trying to repair the damage that causes them. This must change, and it is changing. To me, damage repair is a first and foremost a new, fundamentally different approach to medicine, one that emphasizes fixing things that are obviously broken, which I expect to work much better than the old paradigm of treating diseases separately. The whole “ageing” thing is almost secondary to me. We’ve literally not been fixing people’s bodies this entire time, and now people are finally trying to fix a bunch of obviously broken things, that’s why I’m excited.
I like the parts of the post I’ve read so far, and I’m just making a local argument to this specific bit.
People have been fixing people’s bodies insofar as they can, since the dawn of medicine. They’ve been setting bones, stitching wounds, treating or preventing inflammation and autoimmune reactions, and more recently, destroying or removing cancer and transplanting organs.
What unites SENS interventions is that they require sophisticated cellular and subcellular therapies that depend on the stack of biomedical technologies we’ve produced at an accelerating pace over the last century. Cellular senescence was discovered in vitro a little over 60 years ago, and as recently as 1996, a Berkeley cancer biologist was still writing in Cell that “a limited number of in vivo experiments… strongly suggest that cellular senescence is not an artifact of culture,” i.e. that it takes place in the body, not just in a dish, though the potential mechanistic links between senescence as a tumor suppression mechanism and driver of aging were already well-known. We only sequenced the human genome in 2003, and Crispr-CAS9 has only been around since 2012.
Point being that we’ve been trying to fix people’s bodies for millennia, but we’ve only had the scientific knowledge and bioengineering technology that might potentially allow us to treat the cellular and subcellular precursors of homeostatic breakdown (“aging”) for a matter of years.
Yes we’ve always been trying to fix damage—anything that restores function must fix damage somehow—but it’s a matter of what we consider to be damage, i.e. “bad stuff that we should try to fix because it would restore function”. Historically we’ve focused on trauma, infection and cancer, and although we’ve known about age-related changes like lipofuscin accumulation for a long time, it’s only recently that we started thinking of them as potential targets. Gerontology has historically been a field of basic science, with few gerontologists willing to venture that we could even in principle do something about age-related changes until very recently. They were too afraid to challenge the deeply held notion that ageing is normal, natural and fundamentally immutable. I’m not without sympathy though—anyone who had made that claim would have been attacked and likely would have lost their livelihood—Aubrey de Grey was only able to do it because he was financially independent.
If you look at things like atherosclerosis and AMD, both of which have long been known to be driven by the accumulation of toxic metabolites, I think we could and should have started working on the root causes of these diseases much earlier than we did. Sure, we’re only now figuring out how to remove 7KC and A2E, but that’s because we only just started working on it! Likewise, we’ve known about thymic involution for a long time and it’s always been clear that it damages your immune system in the long run, so why is it that only Greg Fahy is working on fixing it, and why does he get so little funding that his trials have to be funded by their own participants? We declared war on cancer long ago, when our models and tools were still hopelessly crude, and because of that we are further advanced now than we would have been otherwise.
Point taken that this is all extremely difficult and ambitious, and it’s not entirely unreasonable that researchers have been intimidated by that. Rejuvenation is indeed highly dependent on very recent technological breakthroughs, and those new capabilities are a huge part of why this shift is occurring. In my defense, there is a bit where I say
Perhaps I could have stressed that more. To whatever extent there is blame, I place it more on grant committees than on medical researchers. The stuff SENS works on is all high-risk high-reward, which public purse-holders and investors are both cagey about—that’s why it all has to be philanthropically funded. For example, the idea to copy mitochondrial DNA into the nucleus where it is safer (which I ignored completely in the post) has been around for a long time, but SENS had to work on it because no one else would.
Anyway, I don’t want to fixate on whose fault things were. The point is that for whatever reason, we were pursuing a broken paradigm of “one disease one target one drug”, which was never going to work because the diseases were not naturally separable things and their root causes mostly lay in fundamental age-related changes, which we are now beginning to target, and it seems likely to work.
Agreed, I like this elaboration. As I see it, the argument really is that we’ve been neglecting preventative medicine in favor of treating disease after it has become symptomatic. This is a familiar critique that normal doctors and laypeople already subscribe to, and showing that anti-aging medicine is really just another familiar form of preventative medicine (which we have historically neglected) will make more immediate sense than claiming that “we haven’t been fixing people’s bodies” which is only true in the specific sense you just articulated.
Along with that is emphasizing that it’s normal and natural to use preventative medicine. You brush your teeth, you try to eat a good diet and get enough sleep and exercise, you might stake preventative statins or blood thinners or get LASEK. If you’ll do all these things to maintain your health, then why not take low-dose rapamycin? It’s really going to be about normalizing the use of pill-form preventatives at an earlier age, and breaking the association between pills and “being sick.” Instead, it’s about creating an association between pills and “maintaining health.”
It’s both prevention and cure—prevent disease by reversing damage before it gets bad enough to cause problems, but if you already have a chronic disease, then reversing the damage that causes it will be the only way to cure it (though prevention is better of course).
I agree the preventative medicine angle is a good one that people will buy easily, but you can make the same argument against it—that we’ve always been trying to prevent disease just as we’ve always been trying to fix damage.
It’s important to note that statins, blood thinners and rapamycin are not damage repair—they’re not useless, but I think damage repair will make them obsolete. These approaches focus on slowing the buildup of damage rather than reversing damage that’s already there. The problem is that a) this tries to modify human metabolism to “run more cleanly”, which is super difficult and prone to unforeseen consequences and b) you have to take these medicines every day, which makes it all the more dangerous. Statins are well known to have side effects, and rapamycin is an immunosuppressant, which unsurprisingly has a lot of side effects too. You don’t want to take this stuff every day.
The reason people associate things like statins with “being sick” is that they don’t actually make you less sick, they just slow the progression of a disease while causing side effects. Damage repair is far less prone to side effects because it targets stuff that’s definitely not supposed to be there instead of trying to change the way the body works. You won’t get side effects from removing atheromatous plaques (so long as that’s all the treatment does do), but you do get side effects from mucking around with liver chemistry. And because ageing damage accumulates so slowly, you’ll only have to take these therapies every 10 years or so (eventually, once they’re mature). And of course, because it reverses damage instead of merely slowing it, you’ll actually feel, look and be healthier and fitter after the treatment. That’s why I say it’s a new kind of medicine—the public are absolutely not used to medicine that makes them feel younger after they take it.
That’s a reasonable point of view. I don’t think we should be certain that the effects of rapamycin at high doses will be reflective of its effects at low doses, which is why we need to test it. This era is all about precision medicine, figuring out how to control dosing, release, and specific delivery in the context of much better knowledge of how these drugs affect the body to cut side effects and enhance benefit.
The heuristic of leaning toward occasional damage repair by engineered interventions rather than continuous damage slowdowns by manipulating evolved biochemistry makes sense, but so does the heuristic of focusing on an available tool that we have extensive data works pre-clinically right now. I think the “don’t mess with evolution” heuristic is oversubscribed for antagonistic pleiotropy and declining selection pressure with age reasons when it comes to anti-aging medicine.
All the same, I expect that over time we’ll come up with a wide range of both preventative and damage reversal interventions, perhaps along SENS lines. But in that context, a damage-slowing drug (perhaps rapamycin) that might reduce the frequency of the need for damage reversal therapies will be highly valuable, and particularly because it may well be the cheapest and most accessible option to get started, especially in countries that don’t yet have fully developed medical systems..
Totally agree and am glad you wrote this post