Longevity FAQ: A beginner's guide to longevity research
ldeming.com
ldeming.com
I often think about that quote because aging is such an intractably hard problem, we’ve sort of collectively rationalized it as something “good”. You see it in many religious traditions. In the zeitgeist. That somehow death gives life meaning. Makes it good.
But I’ve never found anybody who thinks cancer is a good thing. Nobody sane at least.
I’ve thought for a while now that every philosophy problem is in some sense, just a health problem waiting to be solved.
Occasionally I think about the Bible too and the way Christ (regardless of your religious beliefs) upended this tradition of rationalizing death as good. There’s a line in the Bible that’s the shortest verse in the English version: “Jesus wept.” And he was weeping for Lazarus, a man who died (who he could bring back to life effortlessly); in some sense a true condemnation of death as evil. Something even a god would weep over.
I think about the future often too; the way immortality will finally be achieved. There’s so many complications when it comes to aging, and so much we don’t know about the human body, I wonder whether humans will be involved at all; whether machines will silently develop cures while our bodies lie in a metal tomb, explaining to us what happened afterwards in terms we can understand.
I think it’ll happen someday. But I don’t know if it’ll be a year or 100 years from now.
I certainly hope it’s soon. Some days I feel like I’m at the edge of an eternal history.
https://www.overshootday.org/how-many-earths-or-countries-do...
https://www.overshootday.org/content/uploads/2022/01/How_man...
World population is also a separate axis.
If lifespan is unchanged, population goes up or down depending on rate of new children. Rich and resource-hungry westerners have the lowest reproductive rate. If we get a perfect fountain of youth, we can’t forecast how society will or won’t change. More kids, or fewer?
Likewise resources per person, will we stay in the rat race forever, or shift to working as little as possible as soon as the mortgage on the third mansion has been paid off?
Also, “no ageing” doesn’t mean “immortality”, because current rates imply there’s a 50% chance of dying from accidents or malice in roughly any thousand year period. Though again, no way to predict how that might change with eternal youth.
Resources aren't a fixed notion, crude oil was worthless and toxic before we learned how to refine it and suddenly it's a critical resource.
Natural ecosystems are considered vital today, but if we were to come up with artificial biospheres we would be looking back at the days people got infected by malaria and tick born disease living in uncontrolled environments like we look at people who live(d) in cities without sewage systems.
Anything can be a resource, and be worthless or harmful, depending on the context. Claiming that resource problems can't be solved is a logical fallacy - resources are anything you use to solve a problem.
See but when you're saying this and mention expanding off earth in the next sentence - why do we need soil to produce food ? Or plants even ? Even now there's efforts to process algae into protein etc. It wouldn't surprise me at all that we have specific nutrient production farms via some simple GMO organism in some large scale industrial setting - vertical stacking, ocean surface farms, etc. Compared to space colonisation this seems far less far fetched.
Or the depleted global fish stocks? https://www.fao.org/NEWSROOM/common/ecg/1000505/en/stocks.pd...
Or the fact that if everyone went vegetarian we could free up 80% of the farmland in the world?
Whilst resource are not fixed, like lab grown meats, supplements which can alter people's diets like histidine will reduce red meat consumption, I am aware some businesses have also kept some resources under wraps from the public so I agree they are not a fixed notion, but in ten years the US lifestyle has increased its use of resource from 4 planet earths to just over 5 planet earths.
Sure anything can be a resource, we might even be able to use plate tectonics as landfill waste disposal because everything came from this planet so is technically from the Earth, and who knows what resources could be mined from the planets core, or do we get into mining Helium13 from the moon?
there is a still a problem and that is quality of life, being kept in smaller more expensive livestock pens called homes.
What price do you put on having rolling pastures all around your home and no manmade noise around you?
With a global population set to peak in 2100, we still have 80's years of declining quality of life to put up with.
And yet that's much cheaper and attainable than a small "livestock pen" in a large city :) If you don't mind living without infrastructure - building a cabin in the middle of nowhere isn't that expensive and doesn't seem like there will be a rush to this any time soon. Population seems to be heavily concentrated and the rural areas are being depopulated if anything.
If you take volcanic rock like basalt or granite + water there is every atoms you need to make a human. The rest is a bit of energy.
Is it intractably hard? We already know how to 'rejuvenate' cells for a decade. The field did not receive a lot of attention however, partly because of misguided ethics concerns. COVID changed that attitude
As I take it, that line of thought (that death is just a problem to be solved and that immortality is something to strive for) leads to solving death just before going on to "solve" childhood. Why do we have to be born ignorant of the world and must "waste" some 20 years learning about it (possibly more) before we can go on to be socially productive persons? another 'challenge' for medical science to "fix"...
no, no. I repeat myself, death is not a problem, immortality is nonesense. To percieve death as opposed to life is a consequence (IMO) of thinking with words and only with words; i.e. within language (and logic) these two seem opposite, but there're are ways to think beyond just the logical-linguistic.
I don't think that runs.
you correctly appreciate the structural way in which the argument works.
but you still do not seem to want to see the underlying subltety; that death and life are merely parts of the same larger entity and that our language (our rationalist analytical way of thinking) makes us "miss the forest for the trees", to focus on life and death as opposing rival forces when in fact they're different edges(ends, or sides) of the same larger phenomenon.
Why it being part of a larger phenomenon would stop us from preferring to stay on one side of it?
In most of the universe things are just dead, and stay dead, and aren't part of any process of transformation where death transforms into life. If anything, the "process" of things dying can be part of a downward spiral of more death, and life can be part of an upward spiral that begets more life, and there's all kinds of pertinent details that separate those circumstances.
Life probably started here by underwater volcanoes, and started feedback loops that bloomed more life, and on and on. Meanwhile, most places stay dead and don't become anything.
It's just so frustrating to step into conversations about saving someone's life so they can live to see their great granddaughter's birthday and have someone say we shouldn't because they'd rather play games with metaphysics.
IMO it's rather annoying how the argument usually goes "well, there might be some bigger quasi-mythical reason for things being like that" but they just don't provide any good reason for betting on that metaphysics.
They've decided it's how things should be and often will pull unknowable arguments for it.
And since I'm on the side of thinking we can appeal to analytic concepts to distinguish between health problems that emerge in old age and "solving" childhood with horrific consequences, and you are on the side of seeing them as the same because those distinctions are trapped in strictures of analytic thinking, I imagine that you give your full blown acceptance a pandora's box of outrageous situations. Genocide? Eugenics? Letting global warming happen? Letting war happen? Nuclear bombs? All just the flip side of life, part of a greater dialectic that unites them, and ultimately all fine and good.
Since you reject separating out good and bad cases according to any reading that would have structure, I trust that you embrace this slippery slope just as much as the one you want to attribute to the project of combating health issues in old age.
Not saying it's not a fun game, but if you take it too seriously you're bound to go crazy!
For me, once humanity achieves immortality, that is the inflection point. You are no longer human. You could argue whether one is human may come before or after that point. But for me, this is where I personally draw the line.
Life saving implants, artificial limbs, illness curing/muscle enhancing/brain stimulating steroids, cybernetic/internet connected brain implants, AI merging singularity brain upload, you name it. It's not necessarily bad or good either way. But at some point, you cease to be human (by my definition anyway). And it just so happens that if you're effectively immortal, I consider that obviously inhuman.
In Time
In a future where people stop aging at 25, but are engineered to live only one more year, having the means to buy your way out of the situation is a shot at immortal youth. Here, Will Salas finds himself accused of murder and on the run with a hostage - a connection that becomes an important part of the way against the system.
Personally, I'd rather enjoy old age and go out suddenly than spend the last 20 or 30 so years of my life slowly crumbling to death, so addressing the diseases of aging is a worthwhile endeavor.
He talks precisely about this problem: that by rejecting death and segregating it from life, we end up immortalizing death and suffer from this distinction. And this ontological paradox ultimately encompasses every aspect of Western society: not only how we treat the dead (rise of suicides and euthanasia, and our reaction to it), and soon-to-be-dead (the elderly abandoned in nursing houses), but also the functions of Capital and labour, the breaking down of social democracy, the ever-increasing opposition between the State and terrorism, and the eventual rise of fascism (the perverse aestheticization of death).
All of this is quite complex and I can't do justice here in this single comment, but I highly recommend it if you haven't read it. (I personally think this is Baudrillard's magnum opus, whereas most people only remember him for the book Simulacra and Simulation and the concept of hyper-reality.)
If somehow that were possible for all ages would you be for that?
Then, since death is not a problem we could just “schedule” it for some reasonable date in the future to retain all the philosophical benefits it brings? You first?
How I used to be strong and fast and smart and now I’m a withered husk of a man.
Death is to be conquered like all other obstacles fuck this surrender.
You might want to add another zero there.
[1] https://en.wikipedia.org/wiki/Lifespan:_Why_We_Age_%E2%80%93...
And as to why the child is not formed from bad copies of worn-off cells of a mature parent - it's been some time since I read the book but I think that there was some reset mentioned when a whole new person is formed inside another organism. Fetal stem cells are known to have superior properties.
Could this already be?
Before we knew about cancer, and yes there was a time we did not know what cancer was, was canned good or bad? Did we even see natural death as bad? So where did these constructs come from?
And now I guess you are saying immortality is good? Good for who? Overpopulation is already an issue, imagine if no one died!!
You cannot create a good thing without also creating a bad thing. That is just the way it is.
A larger population, that sees an acceleration in the rate of per capita human capital accumulation, as a consequence of aging being solved, could also be a huge boon for other lifeforms, as it could mean artificial habitats being created outside of Earth where these lifeforms could flourish. It is entirely possible for human civilization to one day create continent sized O'Neill cylinder covered with forests originating from Earth.
Ha! I have heard of people trying to control the world but I have never seen it accomplished. Yes, there are many impossible possibilities that can only be created with fascism.
It also is not mutually exclusive with preserving Earth's natural habitats. In fact, expanding beyond Earth makes it possible to outsource industry and agriculture off-Earth, to allow more of the Earth's surface to be returned to its pre-human state.
Finally, in terms of human-engineered expansion of habitats for other lifeforms, there is the far more durable possibility of terraformed planets. These would require no active intervention to maintain once the terraforming has been completed.
In short, the ascent of human civilization can be, and I would bet would likely to be, a massively positive development for all forms of Earth-based life.
> I often think about that quote because aging is such an intractably hard problem, we’ve sort of collectively rationalized it as something “good”. You see it in many religious traditions. In the zeitgeist. That somehow death gives life meaning. Makes it good.
> But I’ve never found anybody who thinks cancer is a good thing. Nobody sane at least.
This seems to be suggesting that people (have convinced themselves that they) dislike aging research because they have convinced themself that aging is good, which... I just don't think is true? I think most people would like to not get old, but they are just skeptical about this research.
In other words, aging research doesn't have a bad reputation because people are morally opposed to aging research, it has a bad reputation because it's just pretty dismal as science.
A lot of aging research makes assumptions (such as the "programmed aging" theory) that are widely believed to be false by mainstream scientists, simply because that's the only scenario in which it is actually feasible to "solve" aging at our current level of technology.
As Peter Thiel said in that quote, most people want to solve diseases like Alzheimer's and cancer.
The problem with a lot of aging research is that we haven't solved these diseases, and it seems like we simply can't solve them yet because we don't understand enough about how the human body works. We can't even prevent hair from turning gray or (in a satisfactory way) balding. The idea that we can seriously slow or stop aging overall at a point in time where we can't even solve these individual diseases frankly seems pretty unlikely.
"[Death] is Life's change agent. It clears out the old to make way for the new."
Edit: By downvoting without commenting why you disagree, you're only further reinforcing my point. Think about it.
This presupposes people cannot change, which you haven't supported sufficiently with your argument.
The fact that a minority of people are able to adapt their views over time does not change how the general population does not do this.
The quality of the science has nothing to do with it. Being against aging has the same emotional reaction from people in general as pissing in public. That's not how people would react if their issue was with the science.
1. "The fraction of human-level civilizations that reach a posthuman stage (that is, one capable of running high-fidelity ancestor simulations) is very close to zero", or
2. "The fraction of posthuman civilizations that are interested in running simulations of their evolutionary history, or variations thereof, is very close to zero", or
3. "The fraction of all people with our kind of experiences that are living in a simulation is very close to one."
Do you disagree?
This is even more the case in a world on the verge of ecological and social collapse where the age expectancy is lowering.
It's a particularly bad argument here because mitigating the harmful effects of aging would result in massive reductions in medical expenses. Governments and insurance companies would be highly incentivized to get them to as many people as possible.
The argument about medical expenses doesn't make any sense: it's more profitable to have sick people living longer and increare their medical expenses. The failure of the American healthcare system is proof that a market economy is not fit for healthcare.
Profitable for who, exactly? Companies, individuals, the state, or whole society? For that matter, which companies are we talking about?
It doesn't have to be that way, even in our current system.
Metformin was discovered in 1922 and is very low-cost to make. It's available over the counter in many countries but in the US and the EU, you currently need a prescription.
It is on the World Health Organization's List of Essential Medicines [1].
It's used primarily for treating type 2 diabetes. What got noticed is diabetes patients on metformin (on average) outlived otherwise healthy people who didn't have diabetes.
Turns out it activates some of the longevity pathways being discussed on this thread. People on Metformin are also less likely to die from the diseases of old age: cancer, Alzheimer's and heart disease.
Now many doctors are prescribing off-label for patients who want it.
There's a major clinical trial going on to see if aging can be treated with metformin [2].
Metformin costs pennies per day to take, so you don't need to be affluent or privileged to afford it.
[1]: https://en.wikipedia.org/wiki/WHO_Model_List_of_Essential_Me...
[2]: "The TAME (Targeting Aging with Metformin) Trial": https://www.afar.org/tame-trial
Is such an existence worth living? You would be no different than a straw on wind with all its movements explained by physical laws.
Could it be that an idea of self-worth tied to a metaphysical immortal soul stems from an attempt towards acceptance of death? What happens if that death is removed from the equation?
Wishing to continue to experience the world is good but lets say if every activity we do, every desire we have, every thought, inhibition, fear, perception can be debugged external and be shown to be deterministic. That would effectively make us code and probably able to run on machines/simulation. In which case, the whole thing at least for me would seem really to be pointless existence. I mean if all our thoughts, desires, perceptions are just code being run by some giant cpu, then well I'm not going to look forward for the execution of more such instructions (:
I'd separate aging research from attempting to solve Alzheimers, PD, cancer, and other maladies. Cancer is ever-present, sorry to say but most people who read this have some small amount of latent cancer growing slowly. Maybe we will harness the immune system and new powerful drugs and techniques to remove cancer more and more effectively, until it becomes like infectious disease: a threat to all, but usually treat-able.
For aging research, however, we're in a different realm. Assuming someone didn't die from any common malady or old-age related ones, let's say they live to 105. What's likely to kill them then? Well, it could still be cancer, but it could also be solve-able issues like falling and breaking a hip (we could invent machines to prevent or lessen damage from falls). It could be cardiac events, strokes, things where the cardiovascular system has been through so many "duty cycles" that the parts reach their expiration date.
And this expiration date is where I think we'll struggle most. We need to make our hardware last much, much longer if we're to achieve immortality as biological-only entities. The valves of our heart, the vessels of our brain and heart, the operation of the lungs, the sensory organs, the kidneys and bowels: these parts need a lot of extra "lubrication" and "TLC" over our lifetimes if we're to get past the "Age Limit" which is probably around 120 years old.
I'd hesitate to put too much stock into aging research at present. It's in its infancy, and until it ages to maturity, it's going to be an over-hyped area for rich people to dabble in, but I doubt 99% of people living now will ever reach escape-velocity and reach immortality.
Whether you live for a year or a million, our fates are sealed.
There are different theories about the end of the universe such as a heat death or a big collapse. We'll never know with certainty what that end state will be, but that is not something we can escape. (Also, the time frame of these types of cosmic events is incomprehensible to the human mind)
We can and should try to cure all diseases and ailments to ensure everyone has the chance to live as long and healthy as possible. But death is inevitable.
The point is life elongation (in good health).
Slowing or stopping the aging process is the goal.
Interesting that you bring up cancer ...
Cancer occurs when individual cells decide to act in their own self interest and no longer act for the collection of cells that is your body. They ignore cell signaling mechanisms and resist the culling actions of apoptosis, etc.
I agree that cancer is not a good thing. I wonder if individual humans acting to preserve their own selves will be a cancer upon humanity.
Please could you point to a good reference as tumor microenvironment seems to play an important role?
https://en.wikipedia.org/wiki/Tumor_microenvironment
Thanks!
https://podcasts.apple.com/ro/podcast/lifespan-with-dr-david...
> Sirtris Pharmaceuticals, Inc. was a biotechnology company based in Cambridge, MA that developed therapies for type 2 diabetes, cancer, and other diseases. Conceived in 2004 by Harvard University biologist David Sinclair and serial entrepreneur Andrew Perlman, and founded that year by Sinclair and Perlman, along with Christoph Westphal, Richard Aldrich, Richard Pops, and Paul Schimmel, the company was focused on developing Sinclair's research into activators of sirtuins, work that began in the laboratory of Leonard P. Guarente where Sinclair worked as a post-doc before starting his own lab.
> Sirtris went public in 2007 and was subsequently purchased and made a subsidiary of GlaxoSmithKline in 2008 for $720 million. GSK paid $22.50/share, when Sirtris's stock was trading at $12/share, down 45% from its highest price of the previous year.
> Studies published in 2009 and early 2010 by scientists from Amgen and Pfizer cast doubt on whether SIRT1 was directly activated by resveratrol and showed that the apparent activity was actually due to a fluorescent reagent used in the experiments.
> GSK/Sirtris terminated development of SRT501 in late 2010. GSK said it was terminating SRT501 due to side effects of nausea, vomiting, and diarrhea it caused, and because the compound's activity wasn't specific to SIRT1, at some doses it actually inhibited SIRT1, and the compound itself wasn't patentable.
— https://en.wikipedia.org/wiki/Sirtris_Pharmaceuticals
> In February 2022, Sinclair raised widespread controversy in the longevity research community by rejecting to communicate in an academic debate in which his resveratrol research was criticized after months of mounting evidence against reseveratrol as a longevity intervention.
This is the important detail in that story.
People don't just want to live longer. They want to basically do absolutely nothing different than what they do now and also live longer. I wish we at least would frame the problem correctly.
The ultimate "best" outcome would be some sort of intervention that mimics the results of calorie restriction or fasting, but without the sacrifice.
But to get there, we need to study the mechanisms through actual calorie restriction and fasting, both to 1. prove that it works in humans, and 2. figure out why.
- METACRINE -92% (1 year)
- Unity biotechnology -86% (1 year)
- DECIBEL THERAPEUTICS -80% (1 year)
- PRECISION BIOSCIENCES -62% (1 year)
Even your own comment hinted that perhaps we have some more pressing issues to figure out first
It’s always been obvious to me that the problem with singular focus on inequality is precisely this — the easiest way for everyone to be equal is to be dead. This is appalling and a strong argument against a singular focus on inequality.
I would say the same thing about wealth. The easiest way for everyone to be equal is for everyone to be poor. So, make sure your preferred economic policies don’t follow this adverse incentive and just “cut the tall grasses”, so to speak, and just make everyone poor and/or limit upward mobility.
I don't see how my argument is any different from the arguments about us not being ready for general AI because of how much it could concentrate power.
Power is already concentrated, such an advancement would not change the indelible fact that we've reinvented kings and dynasties and we can't seem to get rid of them. Given that life has gotten better for everyone anyway when we discover great things, such concerns must be seen as immaterial. Improving the life of all people is more important.
Final portofolio is (0.1 * 49 + 10 * 1)/50 = 0.29 or -71%
https://en.m.wikipedia.org/wiki/A_Secular_Age
https://ubcgcu.files.wordpress.com/2012/08/taylor-and-immane...
Seeing that you've mentioned Taylor's A Secular Age, maybe I should start reading it (it's been on my reading list for some time, but this renewed my curiosity as his studies seem to be closely related to what thinkers like Bataille and Baudrillard has problematized in political economy)
> this fantasy of immortality poses a devastating problem to Western society.
Absolutely. While I agree with the other commenter that basically no one is against life extension research in principle, the energy that leads to deifying it (which is the vibe I get from a lot of longevity materials) might be better served learning to understand and accept death as a natural phenomenon. I’ve found Seneca’s On the Shortness of Life to be an excellent work on this topic.
Then again, one might characterize the technological successes of the West in the last ±500 years as deliberately ignoring cyclical time in favor of linear “Progress.”
> Seeing that you've mentioned Taylor's A Secular Age, maybe I should start reading it
I really do recommend it. It’s a bit dense but I’ve found the concepts he uses (the immanent frame and the Nova Effect to name a couple) to be extremely useful in understanding the modern world.
For anybody interested, the mTor pathway is really interesting in this regard, and in general the effects of AMPK on cellular metabolism. TLDR is that in the modern world most people never activate these pathways (since we're always in a fed state). Ostensibly there will be some breakthroughs when we finally learn why these starvation pathways are so beneficial. Inflammation seems a decent guess - eating increases it, and fasting decreases it, as a general rule.
I’ve personally starved and seen worms live much longer than they normally do, and regularly found worms in plates months after they should have all died. There’s nothing unnatural about an organism going into “survival” mode when food becomes scarce. It’s clearly something that benefits a species survival.
People want the holy grail, literally. Eat pizza, drink beer while sitting playing video games and take a magic pill that makes you young again.
Obviously this raises a million different questions, such as what to do exactly with the data, and whether it can exist outside it's biological substrates.
But the concept of life as data is worth noting in any conversation about the human lifespan.
This table [0] shows the underlying data. If you plot age against death probability, you get a similarly-shaped curve to the article's.
A sigmoid curve would seem to imply that your risk of dying decreases after a certain age, which isn't the case. I think what you're imaging is a curve that shows one's overall chance of dying at a particular age (rather than risk at a point in time)? Or am I missing your point?
I think I'm going to pass on medical advice from you.
You can read up on "Verteporfin", the patent for cell regeneration (thru "controlled wounding") is already filed by Stanford, pending approval.
healthspan research is clear. 1) inflammation is a natural process that results in wear on your body 2) lower inflammation 3) doing so is different for everyone. behavior is at the core of this process. including eating, sleeping, living a life of non-excessive stress, avoiding and treating major disease, maintaining healthy mouth, and moderate exercise.
so in a word---a lot , but not all , of chinese and eastern medical philosophy has been epidimilogically confirmed.
all the new crap about 'caffiene' 'metformin' and other bullshit being good for you is just that, garbage.
what isn't , is that sometimes some people do have deficiencies of insulin sentitvity, or vitamin D, or other things---like they used to have scurvy ( vitmain C defficiency) -----so these things have been figured out and in no way relate to logevity only healthspan.
the annoying stupid thing about longevity idiots is that if a set of practices and health observation and treatments coudl guarantee living a life of perfect healthy until 100 years old----(assuming any rich person coudl afford this) ---this would yield a total revolution in human affairs for the rest of civilizations existence.
longevity is the dream of fools guaranteed healthspan is the dream of realists.
no one on hackernews is over 60 yet, and this is why all you idiots think with your brains, instead of your hearts. you dont' talk to 80 and 90 year olds, and if you do you dont' empathize with the path towards aging sickness and death. but you will if you don't die healthy and young, because that is what happens to you . guaranteed.
and you will only realize how stupid the idea of living forever is, when you eventually get sick and just want to live healthy one more year. you will realize that feels like forever when it's you. but it's only one more year.
virtually no one lives past 110. focussing on pushing that limit is stupid and longevity research has yielded very little interesting results applicable to other areas.
suspended animation and metabolism research , are , however , intereseting and they are fundamental biological areas of exploration and not 'goal oriented' towards the philsopher's bone. cause that's what it is. a skull bone.