The field of longevity biotech is a mess | Hacker News Reader

The field of longevity biotech is a mess

psblab.org

187 pointsdeegles160 comments

Yes, and the tight timelines of VC and high burn rate of startup funds motivates hype and self-delusion. Longevity research requires a 20–30 year time line even if you are using mice.

But is there good news? Yes: the NIA Interventions Testing Program is an awesome, systematic, flexible, and rigorous effort to evaluate the impact of dietary supplements on lifespan.

And the 10 year studies we have just completed on the genetics of lifespan and longevity in a highly diverse family of mice (the BXD family) provide very strong evidence of gene variants that modulate longevity well after reproductive senescence and under different environments. It is NOT a matter of selection for or against lifespan: it is just a result of high levels of genetic variation affecting all biochemical processes and disease risks. Genetic variants and gene-by-environmental interactions definitely are “in play”. These types of variants are actually inevitable.

Want some references for the smoke-free and half-full part of the glass?

1. Hook et al PMC6066442: Genetic cartography of longevity in humans and mice: Current landscape and horizons.

2. Roy et al 2021 in Nature Metabolism: Gene-by-environment modulation of lifespan and weight gain in the murine BXD family; doi.org/10.1101/776559

3. Williams et al in Cell Systems 2021: Multiomic profiling of the liver across diets and ages in a diverse mouse population; doi.org/10.1101/2020.08.20.222968v2

All of the data from the last two paper is available as FAIR data at www.genenetwork.org. You are welcome to map the longevity loci yourself. Some of these loci operate only late in life—some even after two years of age—roughly equivalent to 60 years and older in humans.

After your trauma at the meeting, read the papers above to know that solid verifiable progress is being made. And smell the ITP roses at

www.nia.nih.gov/dab/interventions-testing-program-itp

Rapamycin and acarbose definitely extend lifespan in highly diverse mice (a robust result) and so do several other dietary additives—at least five others at this point. Resveratrol, as you say, is a failure, and this is confirmed by well powered studies by the ITP.

I think the correct link is www.nia.nih.gov/research/dab/interventions-testing-program-itp ?

Thanks for correction.

This Peter Attia podcast has an excellent review of research into rapamycin as a potential longevity treatment.

https://peterattiamd.com/mattkaeberlein2/

For those who are looking for a summary of the ITP research.

As of Cohort 10, C2014, 7 compounds have shown significant extension of median lifespan:

Aspirin – Increased lifespan in males but not females (Strong et al., 2008).

Rapamycin – Increased mean and maximal lifespan in both males and females when initiated at 20 months of age (Harrison et al., 2009) and when initiated at 9 months of age (Miller et al., 2011). Females responded more robustly than males at equivalent doses; when ~ equal blood levels were achieved, response was also about equivalent in females and males (Miller et al., 2013).

17αEstradiol – Increased lifespan in males but not females, at 4.8 ppm dose (Harrison et al., 2013) and 14.4 ppm dose (Strong et al., 2016).

Acarbose – Increased lifespan in both males and females, but the effects were greater in males, when initiated at 4 months of age (Harrison et al., 2013), but only males responded when initiated at 16 months of age (Strong et al., 2016).

NDGA (nordihydroguaiaretic acid) – Increased mean lifespan in males but not females (Strong et al., 2008), even at doses that gave equivalent blood levels in males and females (Harrison et al., 2013).

Protandim® – Increased lifespan in males but not females (Strong et al., 2016).

Glycine – Started at 9 months. Increased lifespan in males and females (Miller et al., 2019).

Canagliflozin

Thank you so much. Doing Gaia's work. This was the question I had.

How much of the male only treatments was basically make the males less male and reducing their testosterone levels?

Likely most of it. Testosterone is high-octane gas for the body. Burns hotter.

The answer might surprise you a bit.

Aspirin reduce inflammatory response, which testosterone also do. The more likely reason why Aspirin helps to improve lifespans in men is that it steps in when testosterone has fallen through aging, stepping in to do the role of testosterone. High inflammatory response can be quite deadly, especially in connection with cardiovascular problems (a common cause of death for men).

17αEstradiol is a weaker form of estrogen. Men that has either too high or too low amount of estrogen has an significant increase in heart failure. When testosterone goes down during old age, estrogen tend to also go down as estrogen is produced in men through converting testosterone. Again it seems that the drug can help by stepping in after a fall in testosterone.

NDGA (nordihydroguaiaretic acid) is an xenohormone that imitates estrogen. See above about estrogen.

Protandim is a mix of five herbs, including green tea. Can't tell anything about that, and FDA has issued a warning against the manufacturer for false claims.

Interesting!

Fascinating. I know the ancient Romans prized Willow groves, presumably for their medicinal value. I wonder whether this is the reason?..

I don't think the 17a estradiol effect is due to classic estrogenic activity. But probably due to ER-X activation which helps correct metabolic abnormalities in men.

It's pretty easy to extend lifespan in lab mice that live in safe, sterile cages with optimal diets. I suspect those medications all have side effects that would reduce or eliminate the net benefits in wild animals that have to contend with pathogens, injuries, predators, food scarcity, etc.

No, it is not easy. In fact, a large majority of tests have failed in the ITP.

But you are right about the major role of “extraneous” environmental factors, and this is why we started our studies with a systematic perturbation of diet—low fat versus very high fat (citations are above). The correlation of longevity on these profoundly different diets is about r = 0.6 based on an analysis of 76 balanced cohorts of strains on the two diets—about 10 females per strain per diet. With the deep replication (10 identical twins per treatment) these are rock solid data. A correlation of 0.6 gives “explained variance” of only 36% (r^2), so that highlights the major effect of diet on longevity. And the gene variants that modulate longevity on the two diets are, as expected, very different.

Bottom line: the genetics of longevity is the genetics of gene-by-environment interaction—your major point.

I see that Rapamyacin is a mTor inhibitor. From my years of lurking r/fitness my understanding is that is the “growth pathway” that you want to activate for muscle building (with whey for example). But it doesn’t look like people with more muscular mass die early, even the opposite. Am I missing something?

I would guess they do die early compared to people of the same activity levels, they just tend to get so much more exercise than average that the effect is overwhelmed.

People who are healthier have more muscle mass but adding muscle mass doesn't make you healthier. Muscle mass is a signal of health not a cause. You can look at bodybuilding lifespan for proof. Lots of bodybuilders die young despite adding on enormous amounts of muscle.

You can see the same with testosterone. Men with higher testosterone live longer but giving people testosterone doesn't increase lifespan.

Caakg: https://www.aging-us.com/article/203736/text

Banting and Best came up with the idea for synthetic insulin, tested it on themselves, tested it on animals, tested it on comatose diabetic children, developed and released a commercial product, and won the nobel prize in a span of 3 years back in the 1930s. Doing things on this kind of timeline now would be totally illegal and they would have lost their medical licenses and been thrown in jail no matter how well the whole thing worked.

Longevity science overseas is embracing this no rules, we want the future now, kind of mentality. It's amazing what Bioviva has done with adult gene editing. It's probably some of the more underreported science news in modern history. I could see Bioviva getting shut down by the feds and gene editing for longevity going back to the realm of stuff we don't have anymore like the Concorde or a moon landing capable space program.

Diabetes is a near term fatal condition if untreated. Dying of old age isn’t.

Pretty sure dying of old age is a fatal condition if untreated. "Near term" being different depending on your age, but if you're 94 and male, you have a 3 year life expectancy, so pretty dang near term.

Near-term being key. And most longevity work involves early intervention.

Convincing the FDA you need to dose a 5-year old with an experimental compound so they live until 100 instead of 90 isn't going to work.

Yes, but you can't convince the FDA to dose a 95-year old either.

Sure you can if you’re addressing a disease of aging.

Nontrivial numbers of people not dying of old age would also present some complications for society in general, without adequate planning. Anyone interested in seeing life extension being brought to market would be well served by addressing those issues.

I don't buy this argument. First of all, the implication is that by increasing lifespan we'll increase some other kind of cost. I actually suspect it would be entirely the opposite - that by increasing lifespan we'll increase healthspan, massively reducing healthcare costs, increasing years where an individual is an economic boon, etc.

Second, there's a huge difference between "we've made everyone immortal" and "we've increase average lifespan by 5 years". If average lifespan goes up 5 years I don't think we will have a ton to worry about in terms of "oh my god there are SO MANY more people!" etc.

So I just don't buy it being this huge thing to plan for.

What's interesting about longevity medicine is because of these ethical considerations there aren't billions sloshing around fully occupying all interested researchers like there would be for something like Alzheimer's research. This makes the field more interesting because there aren't the usual big players funding research and vacuuming up all the talent.

> The notion that somehow aging is “special” and therefore shouldn’t be regulated like “normal” diseases is not convincing. The same argument could be made about any number of other conditions. For example cancer – for years we’ve been told it’s not one disease but hundreds of diseases, and therefore we need to think about it differently. And yet, cancer medications including personalized therapies such as CAR-T seem perfectly capable of getting approved within the existing framework of the FDA.

This seems to miss the main point about regulation that the longevity researchers face. Aging is not recognized as a disease by the FDA, so aging treatments are not allowed to have the same treatment and development pipeline. To 'be regulated like “normal” diseases' is in fact what many longevity companies would benefit from.

> Aging is not recognized as a disease by the FDA, so aging treatments are not allowed to have the same treatment and development pipeline

This is valid but immaterial criticism. There are no treatments reaching their clinical endpoints in a rigorous way. The FDA isn’t blocking anything because nothing has made it to its level. That makes complaining about the FDA putting the cart before the horse at best and a red herring for certain personalities at worst.

There's no need for the FDA to recognize aging itself as a disease to get a therapy through clinical trials. If you have a working aging-prevention or aging-reversal therapy, pick one of many age-associated diseases like arthritis or osteoporosis. Run a trial showing that it successfully and safely treats that specific condition. Once it's approved for any condition it can be approved off-label for other conditions by a willing physician.

I regret that this is not a very good article.

For context, I'm not a biologist, but have joined On Deck Longevity Biotech - maybe half the people have biology PhDs, and everyone is interested in (obviously) longevity biotech.

Yes, there is more money than ever before flowing into biotech in general, including longevity. Why?

For one thing, just a few years ago, people like Aubrey de Grey had successfully branded the field as fit only for crackpots and mediocrities (to be fair, some good people got into the field through de Grey's work, but I am not a fan).

Now longevity (or anti-aging, or whatever you want to call it) has attracted many very legitimate researchers, in part thanks to Laura Deming. However, the field is worried about an "AI winter" - there's awareness that someone or other needs to deliver a working drug in the next decade or so to avoid investor flight.

Here's where I don't get the article's critique: the author lists many new companies, none of which have yet delivered a working anti-aging drug. Sure - but why is that a problem? Scientists and investors alike are well aware this is a new and speculative field.

No one legitimate is promising a working drug. They are promising research, which is normal in biotech (big pharma has largely outsourced research to biotech startups).

What is worth debating is the time horizon. These companies are indeed formed on the belief that there's a reasonable chance of a working drug in the next decade or two. If that pans out, of course it will change the culture at large, make billions, and the field will explode.

If there's no such reasonable chance, then yes many of these companies shouldn't exist.

I was very pessimistic about the chances until I read more of the science, and now I am more optimistic that in a few decades we may see a drug that extends healthspan by say 5 years.

Finally, I will note that "90% of anything is crap" and there are many useless and scammy companies and "researchers" in the field. Just don't throw the baby out with the bathwater.

Agreed, article seems to be of the "vaguely rambling against everything" genre, and of little substance.

For instance, what is the paragraph mentioning Aducanumab and ivermectin even trying to say?

Sometimes I enjoy these articles that are strawmen, because then you get an interesting discussion about the topic on HackerNews.

I'm not in that field at all but Aubrey de Grey keep saying that since they try to solve or slow down illnesses of old ages,the worse that can happen is that if they fail at curing aging they'll have at least reduced the impact of some illnesses.

Interesting post!

Small comment on the argument against anti-aging genes existing: "genes only propagate if selected for, and there’s no selective pressure for longevity after reproductive age" (I know that this was just a very minor aside, but I still think it's worth pointing out the flaw.)

That's not how evolution works. Even after you have reproduced, you have impact on whether your children survive and reproduce. This means that there could very reasonably be evolutionary pressure in either direction (causing people to die younger that way they stop taking resources from their children or causing people to live longer that way they keep providing support for their children).

This idea is called group selection [0].

Edit: perhaps kin selection [1] is the more appropriate one here.

Still, longevity would affect the group and not only the direct kin.

[0] https://en.m.wikipedia.org/wiki/Group_selection

[1] https://en.m.wikipedia.org/wiki/Kin_selection

More like kin selection: https://en.wikipedia.org/wiki/Kin_selection

Effect size is hardly ever zero and surprisingly small effect sizes can be measured. But is this evolutionary pressure large enough to make a difference for a longevity gene when people already live quite long after having children?

I think the idea is that there aren't "longevity" genes only aging genes. Put another way, aging isn't an accident caused by the accumulation of damage. It's a selected for trait, a sort of slow, whole body apoptosis used to get rid of the soma once it's served it's purpose. Lifespan is simply the well timed removal of a generation once it has had the opportunity to reproduce and raise its brood.

Perfect! And reproductive longevity is strongly selected. Mole rats and bats, despite small bodies and quite high metabolic rates live far longer than might be expected from simple allometric relations. Reproductive lifestyles can evolve by bootstrapping on large numbers of DNA variants that modulate and molecular-cellular systems.

I’m not sure I buy that completely. If this were a neutral choice, why would a gene take the 50% chance of not having made it to the next generation? (Or in the case of many offspring, invest half its resources into a different copy of the gene?)

At least in mammals, killing the soma is on the surface such a massive waste of resources that I believe it must be either: (a) biologically implausible to keep an animal reproducing for a longer timespan or (b) caused by mechanisms that are counterweighted by massive reproductive benefits while the animal is young.

> killing the soma is on the surface such a massive waste of resources

How is it a waste of resources? Evolutionarily, the goal is to produce another successful generation who then begets another generation and so on. The rate at which that happens is a balance between what is necessary to confer the best chance of survival to each child, the number of children needed to outweigh the mortality rate, and the required mutation and crossover to adapt to the environment. Keeping the same individuals in circulation longer doesn't confer an advantage to their offspring since they already posses the same genes. It would more likely hinder the propagation of their genes by taking resources away from their progeny and competing for mates, territory, status, whatever.

The balance point being to live to provide care to the grandchildren while the children are in the height of their career, then die off in order to free up resources?

That’s plausible, but there might be trade-offs involved. There’s a theory — not sure how serious it’s taken by experts — that at least some of the mechanisms involved in aging have other benefits. For example, the fact that telomeres limit the number of cell divisions might also be a defense against cancer. A mutation that increases lifespan at the cost of this mechanism could be a net negative, from an evolutionary point of view.

It's also a factual error. There have been longevity genes discovered. Cynthia Kenyon famously doubled the lifespan of a C. Elegans by mutating daf-2: https://www.nature.com/articles/366461a0

Also simply because there is no selective pressure for a gene does not mean it does not exist through pure chance.

There's an anecdote from AIDS research that I'm frequently reminded of. People started off not knowing what was causing symptoms, then they began to understand the virus, then they started to produce chemicals to attack HIV, prevent its spread, reduce it's harmful effects, until one day when results of a study of a cocktail of these drugs was released showing dramatic reduction in symptoms and increased survival rates. People in the audience when the results were presented had access to these drugs individually and went home and started taking the cocktail regime themselves. They got better.

This was only the successful path, along the way innumerable theories were tried and refuted, chemicals produced which did nothing or caused harm, and hopes were raised and dashed over and over.

Aging research is in the world before solid theory, before we understand the many causes, but chemicals are being developed and people are taking them. It might be that one of the proposed theories is right, and self-medicators will be the first to know. More likely though is that it will take years and billions of dollars in basic research to develop good theory and better drugs.

Unlike HIV/AIDS there probably won't be a single cause and aging (by definition) doesn't impact a young, healthy, active population. In fact, we are so conditioned to accept aging as normal the fight for resources is the fight to convince funders that there is a problem worth addressing. It's a pretty big, and terrifying, mindset change to go from "death from old age is natural and to be accepted" to "death from old age is preventable and tragic."

To kill something, you need to know one way to do that. To keep it alive, you need to avoid _all_ the ways of killing it.

I think that is a strong argument for preventing aging being a much more difficult problem.

Not really. It’s more of a “how do you eat an elephant” problem. Answer: one bite at a time.

We’re doing that, even without the anti-aging label. E.g., things we now call “preventable deaths”. Even within that label, there’s a lot of opportunities that are far more tractable than others.

Not really. Longevity research is about significantly extending the healthy lifespan. What we’ve done so far is increased the likelihood that an individual will live as long as the longest living human. But we haven’t meaningfully increased the lifespan of the longest living human. Theoretical human lifespan is about the same it has been thousands of years ago.

That onky gets us so far. Mostly just extending us to the limits of our natural lifespan with aging included.

There will have to be direct work on tje processes that lead to aging. Audrey degray has a good ted talk on what he belives are the primary processes that cause aging. Seven of them i think and all of them are vastly complex

I don't feel like you can treat aging as simply a sum of its parts.

Sure, there are some major causes of age related deaths like heart disease that we can work on and potentially expand average lifespan by a few years. However, the core problem of aging is probably best thought of as a disease in and of itself, where the things that actually kill you are symptoms.

We need to make progress on the underlying mechanism that makes us more brittle over time.

I'm reminded of the story about Henry Ford asking which part never broke down, and then using that to cut costs -- maybe evolution is like that too, and once we fix one problem we'll find the next isn't far behind?

Except now that I've searched for a link for that, one of the first results actually questions that story, ha! https://johnhawks.net/weblog/topics/urban_legends/henry_ford...

Insightful take on it. Yet to be seen whether age halting/regression goes the path of HIV medication or the perpetual motion machine that humanity has likewise spent significant effort to attain.

I get what you're trying to say, but it's not that hard to make a perpetual motion machine if you're willing to keep putting energy into it. It's just hard to maintain, which is a much better match for aging research.

The perpetual motion machine analogy is quite apt, because fighting aging is ultimately fighting entropy. Both are doomed to fail in their quixotic battle against thermodynamics.

This is a common misconception about the second law of thermodynamics. That law implies that all life must eventually starve to death if nothing else kills it first, because the universe will have run out of usable energy. But as long as the energy supply lasts, non-aging life forms are possible. (Bacteria are arguably an example.)

I recommend spending some more time understanding the second law of thermodynamics.

You're the one who needs spending more time understanding it, as you obviously have no clue.

If what you said was true then life itself couldn't exist.

If you take this stance you might as well start arguing for the extinction of humanity and destruction of earth. After all everything is "doomed to fail in their quixotic battle against thermodynamics".

A classic is/ought distinction error.

Observing reality is not the same as prescribing a particular course of action.

Your post heavily implies anti aging beeing futile. Likening it to the search of a perpetual motion machine. I fail to see how this is not heavily suggesting a course of a action.

I keep wondering how the pandemic will affect public opinion. I think it’s an opportunity. Excess deaths and total death rates are being reported to wide public for the first time. Czech Republic is one of the worst affected countries, it has at times doubled it’s monthly death rate. If people mourn and are angry about the half that died from covid, will they be more opposed to the other half dying of other causes (most related to aging). Covid of course is linked to aging as well.

I wonder, but I’m not sure. The “death is a natural part of life” is an extremely strong narrative, a coping mechanism really.

Death of old age /is/ a natural part of life, but so was high infant mortality until we found solutions to that. The problem is that until we actually have solid proof of anti aging science, people will continue to believe it's part of life.

Its always been astounding to me that these muti billionairs we have today put so little of their vast fortunes into research for something that will 100%affect them.

I know one of the rockafellers was into life extenssion big time but he died of old age (91) a few years back. Im not sure what kind of legacy he as left if any on that front as far as funding. I fear his death likely set back research by decades though

Billionaires either have to volunteer to be the guinea pigs for radical experimental anti-ageing therapies or accept that by the time treatments are proved safe and somewhat effective it's probably going to be too late for them. And if it isn't going to save them, there's plenty of strong competition for their philanthropic dollars, some of it with impressive results.

Surely it's not hard to come up with ways to avoid being the guinea pig. Find multiple aging based ailments that have lots of patients and fund a study.

The issue is that you will get the results on the subjects after your life is over or coming to end, unless it is the case that we could make life of a person currently >60 years old long which seems unlikely to me. So you would have to wait for 40 years before you know the results with good enough certainty.

Zuck is still relatively young. Maybe he'll become our first immortal overlord.

Seems to me if you life is coming to an end that would increase the urgency. Remember money is not an object here it is basically just will to do it. The money is irrelevant. There is also the possiblity of increasing quality of life even if it doesn't save you.

I mean do nothing 0%, do something and any chance is better. The money doesn't matter.

Won’t help much. I read that if we cure all types of cancer it will extend average life expectancy by just over a couple of years. Because if not cancer then something else will get you in old age. I guess if cancer did not affect younger people then we wouldn’t have cared about curing it as much. 8 year old with leukemia looks a lot more dramatic than a 80 years old :)

I'm not sure that's true. There are plenty wealthy twenty somethings. I don't think it's out of question anti aging treatment bears significant fruit in the next 70 years.

There is no requirement to be a guinea pig for the research. Why do you think that?

My whole point was if you have more money than god what is a few hundred million to setup a research lab for something that will definitely kill you? If I knew an army was coming to kill me and I had no hope I would still start using my billions to rally some sort of defense. Why sit around and do nothing when I have resources sitting idle?

well, the conditions of the society you live in also 100% affect you. So contributing to things you think will improve this is just as logical.

the whole point of obscene wealth is it allows you to shield yourself from many of the conditions of society that less wealthy people must suffer, at least as long as society itself allows this. The dying of old thing seems more a thing they should be concerned with.

Jeffrey Epstein is known for his interest in and material support for longevity research. Let’s see if he outlives Rockefeller

He was also known, among scientists, to be a charlatan and relatively stupid about the science (relative to his pretensions). So he probably wasn't allocating the funds very well.

> Let’s see if he outlives Rockefeller

lol

With all the money he has, he could even fund research in sexual pathology, suicide, and conspiracy prevention.

He proved that blackmailing the rich and powerful shortens one's lifespan.

One of the biggest arguments for radical wealth redistribution is just seeing what people do with their money.

And the pandemic and the billions that have been spent/redistributed in "relief" answered that question: watch Netflix and make TikToks.

There is a confounding factor there: deadly disease necessitating people staying home

but they do...

https://www.cnbc.com/2021/09/21/silicon-valleys-quest-to-liv...

'Amazon’s Jeff Bezos, Alphabet’s Larry Page, Oracle’s Larry Ellison and Palantir’s Peter Thiel are just a few of the super-rich who have taken a keen interest in the fast-emerging field of longevity`

Regarding Google / Larry Page: https://en.wikipedia.org/wiki/Calico_(company).

has this company done anything note worthy since 2013?

I've seen some of these but they all seem to be operating quietly like some zero sum I live forever you die game. That is not going to work. The amount of money they have life extension should be encouraged as a college major. People still barely think about it as a serious avenue for their life direction.

> aging (by definition) doesn't impact a young, healthy, active population

There's actually a rare syndrome, progeria, that does cause aging in young people and this will likely provide insight toward solving aging https://www.mayoclinic.org/diseases-conditions/progeria/symp...

To your larger point, I would agree that self-medicators will be useful too. Can't that be true at the same time as the problems described in the article?

It's a pretty big, and terrifying, mindset change to go from "death from old age is natural and to be accepted" to "death from old age is preventable and tragic."

But arguably it is natural because .. it's what our organisms are designed to do.

That is, we're not "designed" (I mean by evolution, of course) to have lifespans beyond 100 or so years. We're specifically optimized to have about two or three decades as healthy, independent adults (from age 20 to about 40-50) which are devoted either to (1) raising children or (2) contributing to the welfare of the species or tribe as a whole.

That is -- we're specifically designed and optimized to promote the longevity of the group, not the individual. In fact, individual longevity is explicitly sacrificed in favor of group longevity.

That's just how we're built. And that's what's why longevity research is (apart from all the unknowns) fundamentally different from, say, finding research for cancer or AIDS. The latter group are unequivocal dysfunctional states ("preventable and tragic" if you will), and the basic goal of the research for these cases is to return the organism to it's correct, functional state.

But aging (with its inevitable end state), on the other hand... is the organism's "correct, functional" state. So to find a categorical "remedy" for aging (beyond extending its horizon for a decade or two) is not to merely find the right "correction" for a certain set of dysfunctional states... but to alter the organism's functional nature entirely.

That's why it is categorically a completely different beast of problem than, say, finding a treatment for AIDS. It may also be "terrifying" to our poor psyches strapped into these inevitably self-destructing organisms -- but to the collective goal of our DNA (that is, to promote the group over the individual -- it is also entirely moot.

You'd be saying the precise same thing if our natural span was 30 years, or 200. That is, you're using our current state, to explain why our current state exists.

You'd be saying the precise same thing if our natural span was 30 years, or 200.

Well, yeah.

That is, you're using our current state, to explain why our current state exists.

Woah there, that's a big misread of what I was saying.

I'm not using the "state" (the number X of years that is the currently observed natural lifespan) to "explain" the value X. But rather the intrinsic design and function of the system as a whole.

There's a huge difference there.

There is nothing "correct", "intrinsic", or "functional" about aging. That's conflating evolution with lack thereof. We evolved to sustain a reproductive cycle and propagate ourselves. That evolutionary optimization has no direct bearing on the specifics of how we age. What we know about aging so far indicates that it's an accidental byproduct of many side effects of the functions of our systems, including the hormonal system that governs puberty, the immune system, the metabolic system, and the higher order DNA management systems (epigenetic programming and replication). None of those side effects are in any known way selected for by evolution, and most of them seem to be tunable to achieve far more durability or regenerative capacity out of our bodies than we are currently used to. Multicellular aging is a collection of random side effects that vary between species - there are many animal species that are effectively immortal.

Please see my response to the sibling comment, in which I attempt to respond to both of these critiques at once.

My point is, you are inside the system, using values from the system, to explain the system.

If humans lived 200 years, but went infertile at 50, you'd be explaining how the system was designed to entice grandparents to care for grandkid's babies, because they were infertile and couldn't have their own, and because it would improve their genetic bloodline's chances.

I still feel much of your reasoning was using what is, to explain why is, because what is.

This response applies both the above and its sibling comment, which are quite valid in asking that I should perhaps clarify further. So if I may:

Yes, our current "operating mode" (with an apparently built-in expiration date at roughly 2x peak fertility) is but one of (infinitely many adaptively stable configurations ("local minima" as it were, in the fitness landscape). It is by no means the only possible (let alone the best possible). As the above comment points out, we can easily imagine other operating modes that are also viable and stable.

But the basic point I was trying to make is: though it isn't the only possible mode of operation for our species -- it is also far from random, and most likely the result of many interlocking tradeoffs in our basic genetic program (which we are just beginning to map out and understand).

The upshot being -- my hunch is that, while we will probably figure out how to tweak some of the dials, attaining a substantially different mode of operation ("longevity for everyone", basically) will require changes substantially beyond tweaking of dials -- or a "patch" here and there. Most likely it will require something akin to a top-down rewrite (or that is, a comprehensive rewrite of many interlocking mechanisms at once). Which will require not only conceptual advances, but to be blunt, "trial and error" (live trials, most of which probably won't work out so well for the test subjects).

That is to say -- qualitatively different from merely deriving a "patch" to our system sufficient to, say, obviate the risk to certain diseases like dementia or cancer.

>from age 20 to about 40-50

Really? Just that range? Not sure about your own family history but the vast majority of 50+ and 60+ year olds I know are quite healthy, vital and fully independent, perhaps more so and especially more independent than many people in their 30s and 40s even due to greater accumulated assets and self care. There are many exceptions of course but most people in developed places seem to live quite well and independently into their 70's even these days.

I just mean that "societal contribution" (that is, towards group fitness) peaks in the age window, on average.

After age 50 or so many of us may be living perfectly well, but by and large, we're coasting (or at least slowing down).

Agree. I'm in my mid 50s; I figure anything more than another 15 years or so is a gift. That doesn't sound like a lot of time in retrospect; thinking about 2006 does not seem like very long ago to me. So there's a growing sense of there not being a lot of time left, and a stronger desire to spend it on simple things that give me satisfaction rather than building more software that will be obsolete before it's really even finished or learning new technologies that will be "legacy" by the time I can really be productive with them.

At the same time I have zero interest in longevity. I will live the life I've been granted, for as long as it lasts. Then I'll get out of the way.

I think you're ignoring the "to be accepted" part of the text you quoted. Just because something is what we were "designed" for or how we lived prehistorically doesn't make it right or desirable (nor the opposite--in this case fighting aging--wrong or undesirable).

You're right I am, basically.

I offer no insight as to whether the finiteness of our lifespans is "right" or "desirable". And I certainly am not saying that fighting aging is wrong or undesirable.

Just that there's a structural reason as to why our organisms are built the way they are -- and a pretty deep structural reason at that.

Yeah biotech by its nature is super iterative and has fits and starts and takes a long time.

I find it interesting to read old publications. It gives a sense of what arguments are new and what are re-treads.

Here's an essay from Eugene Garfield from 1983 titled "The dilemma of prolongevity research -- Must we age before we die, or if we don't, will we?" at http://www.garfield.library.upenn.edu/essays/v6p107y1983.pdf

> Medicine men and magicians, alchemists, sages, and physicians have searched for ways to ward off the effects of aging. But to date, scientists and their predecessors alike have been rebuffed. ...

> Why has the problem of aging been such an intractable one? Up until recently, the prevalent view of scientists had been that the task of controlling aging was fundamentally impossible. But today, such a consensus no longer exists. Many researchers now believe that their predecessors failed, not because their goals were misguided, but because the tools and the level of sophistication they could bring to the task were inadequate. Moreover, it is argued that progress has been hampered because funding has been scarce, and researchers concerned with aging have been too few and far between.

> Indeed, until recently, aging research had been plagued by all of these problems. During most of the first half of the twentieth century, while rapid progress was being made in other areas of biomedicine, only a handful of scientists throughout the world were doing aging research. One of these pioneers was Nathan Shock, who, according to Paul D. Phillips, Wistar Institute, Philadelphia, is considered by many to be one of the “fathers” of modern gerontology.

> Growing public and private support for aging research reflects the scientific community’s own increasing commitment. Today, aging research occupies unprecedented numbers of highly talented individuals, not only specialists in gerontology, but researchers from other disciplines as well. These include biochemistry, endocrinology, immunology, neurobiology, genetics, and cell biology, to name only a few.

Garfield then lists a number of books advocating longevity research (Ettinger's 1962 "The Prospect of Immortality"; Barrington's 1969 "The Immortalist" ; Comfort's 1964 "The Process of Ageing"; Rosenfeld's 1983 "Prolongevity"), praises the increase in federal funding in longevity research, mentions private sector organizations funding aging research (The American Longevity Association; The American Federation for Aging Research) and lists similar organizations in different countries.

He then writes for a few pages more about the current status of longevity research in 1983, written for a technical but non-specialist audience.

With an additional 40 years of research, what progress has the field made? I don't know - I claim not even the basic of expertise in the area.

But what I can say is that certain arguments sound hollow after being repeated for decades with seemingly limited success.

We can anyway say now that sulfur-containing amino acids figure somewhere important.

Can you elaborate on this?

It has long been known that restricting the diet of many kinds of animals made them live longer. The cause was more recently narrowed down to two sulfur-containing amino acids, methionine and cysteine, such that restricting only those extended the lifespan of test animals.

Experiments restricting primates' diet have failed to replicate the effect seen in other animals. Humans already live much longer than other mammals of similar size.

Very interesting, thank you. Are there any leading theories on why this works with some mammals but not primates?

There are many hypotheses, but no way discovered yet to check them.

I'm curious about the state of research on longevity for model organisms. Especially C-Elegans, or something else comparatively "simple" to a human. If we can't manipulate lifespan significantly in those, I don't see much hope for it in humans. Phrased a different way: I think extending flatworm lifespan is a prerequisite for extending human lifespan, at least in a systematic way.

I'm not optimistic we'll have real breakthroughs in this field within the next century or so, but the gut reactions to the field (See the acerbic tone of the linked article) are born more out of a knee-jerk reaction to what longevity research implies, than a rational take. When the arguments go towards societal sustainability or "I wouldn't want to live any longer than 90", it's a cue you're reading a skin-deep reaction.

Experimenters have been able to extend the lifespan of C-Elegans five-fold by modifying just a few genes[0], though its unlikely that research will translate well to humans. Even interventions in much more closely related mouse models frequently fail to translate to us, but must biologists will agree with you that those organisms are the place to start.

[0] https://www.buckinstitute.org/news/five-fold-lifespan-extens...

Yes, good question!

We have good results for c. elegans, mice, and fruit flies. These have all had their lifespans extended by quite a lot for c. elegans, or iirc about 40% for mice.

This, and the existence of several multicellular organisms that do not appear to age, is the basis for optimism for eventual success in extending healthspan. Like, so far we haven't found any fundamental biological reason that living longer is impossible.

(it is worth nothing that Blagosklonny's paradigm of programmed aging seems to me to lead to more pessimism, but I don't know if he'd agree)

Matt Kaeberlein's Dog Project, and Celine Halioua's company Loyal, are both focused on extending dog lifespan, as a much larger model organism, but are not there yet.

I also agree with your second paragraph :)

You might be interested in this paper, "A collective analysis of lifespan-extending compounds in diverse model organisms.[1]" Interestingly, common substances like aspirin and minocycline had a large impact on lifespan in the simple organisms studies. This seems to be due to a systemic impact on the organism's function and ability to heal from age related degeneration.

https://pubmed.ncbi.nlm.nih.gov/34687363/

YMMV, but a significant amount of real-world and statistically significant contributions can be made to average human longevity by focusing on paths of least resistance, such as tackling gun and car related deaths, then on the individual+average longevity by looking at preventable-but-chronic conditions (such as diabetes) by regulating things like common pollutants, added sugars to foods, and having better access to the outdoors and exercise/activity. Then you can enjoy a long life that will - on average - be healthy and long enough and with decreased risk of dying early. Past that, a lot of the research feels like “solutionism”.

Very interesting to get a sneak peak into this world.

Over the past year I've been digging deep into research around similar topics but revolving around protocol first changes, with supplements as an optional add on. I had some crazy symptoms develop after realizing I wasn't sleeping enough / properly. Fixing my sleep hygiene and eating habits changed my life. I wonder if more research was dedicated to recovery if this would help the field progress faster as it seems to be the key to preventing and healing all of the major causes of death.

If anyone is interested, I stumbled onto this research through professor Andrew Huberman on YouTube. Amazing, life changing stuff.

Huberman is the real deal.

Most longevity biotech companies are following a completely wrong course. At best they might develop some compounds which provide marginal lifespan gains for a subset of people along with negative side effects.

The most effective way to actually increase longevity is by delaying the onset of chronic diseases such as hypertension, diabetes, sarcopenia, and arteriosclerosis. If you look at people who actually live past 100 they don't live any longer than others once they have chronic disease. Instead they experience disease onset later in life.

And we actually already know how to delay most chronic diseases fairly well. However the interventions aren't consistently applied and patient compliance is often poor.

I respectfully disagree - many diseases are diseases of aging, in that they appear only when someone has aged significantly.

A drug that increased healthspan would thus treat multiple diseases at once. And in fact, since we still do not have reliable aging clocks - in other words, a good way to tell if a drug has made you younger - one way to assess whether a drug may be treating aging at its root is to see if it is treating multiple diseases at once.

A drug that improved outcomes for multiple diseases might turn out to be an anti-aging drug, is the idea (of course, there is no such drug yet!).

Anyway, the logic is that instead of delaying multiple chronic diseases separately, we go after aging, which should have that effect anyway (for many people, and for many diseases, but certainly not all).

That's just silly. You're basically talking about a magic drug which doesn't exist even in concept form. It's the equivalent of wishing for cheap fusion power or room temperature superconductors or warp drives.

Instead of scifi fantasies, how about working towards something actually achievable?

No it is not silly—Coyotespikes is correct. There are fundamental aging processes that increase risks for many later onset diseases. Finding common denominator molecular causes of aging is the right direction for longevity research. Much current work is focused on mitochondrial facets of aging as that possible common and causal denominator. And it does make sense to maintain optimism about solutions.

Finally: we all currently live in a scifi fantasy world.

Yes, exactly so!

Also, we have already been able to find "magic drugs" for mice, worms, fruit flies, yeast, and other organisms. Currently Celine Halioua's Loyal and Matt Kaeberleine's lab are working on doing the same for dogs - a huge step toward doing the same in even larger mammals, humans.

Finally, saying the drug doesn't exist in concept form simply reveals complete ignorance of the field of aging research. In fact we have an embarrassment of riches! There are multiple competing paradigms, which each suggest a similar but different mix of therapeutic modalities.

We have David Sinclair's paradigm of information loss via analog epigenetic decay, Blagosklonny's paradigm of programmed aging, DNA loss approaches, the very exciting idea of senolytics, partial reprogramming (a hot one), and others.

You might read Jose Luis Ricon, or Laura Deming, for a quick overview of the subject.

I think we will see the first drug approved specifically to treat aging by 2030 or 2035. Considering how long the current stable of candidates will take to wend their way through the pipeline, that's a pretty optimistic prediction. It will not be a one-and-done deal, but something that will make a difference.

The only very good news I have encountered lately came out in April, where a cohort of tens of thousands of US Veterans Administration patients were found to suffer 40% less incidence of dementia if they had got a recent Tdap booster.

Nobody knows what was in the booster that made the difference, but it is very hard for a confounder to produce a 40% effect size. (I doubt aspirin would get such an effect size.)

A Tdap is safe, and I don't need to know why it helps, only that it (apparently) does, so I went right out to the drug store and got one.

I expect at least some of the billionaires are getting transfusions of blood extracted from infants. Which infants, I hate to imagine.

>> genes only propagate if selected for, and there’s no selective pressure for longevity after reproductive age

Because humans are not social animals? Because protecting your own offspring as long as possible is NOT a thing?

Everything with even slight benefit is selected for to a degree based on that benefit.

Having parents is beneficial. Having grand parents is probably also useful. Having great grandparents... well someone has to get eaten by that lion.

there is a fundamental problem here. You can guess if some longevity biomarker has a causal effect; but in the end they are only guesses. Suppose your desired endpoint is a human lifespan of 150 years. And you start experimenting on 50 year-olds, now. You cannot truly know if your intervention will work for another 100 years. At best we can start doing interventions on shorter lifespan animals (say, dogs) but there's still no guarantee that the causal factors for dog death match up with those for humans.

Not to mention the fact that even if it works in removing some ageing factors, most of your cohort still probably ends up running into the sort of ailments that terminate most people's lives before the theoretical limit to their lifespan. And those other ailments represent challenging, but more easily testable medical problems to solve first

This feels like saying that a five-year MTBF estimate for a disk drive is meaningless until it's been tested for five years. No, we don't truly know if the estimate is correct, but nothing in life is truly known: some level of evidence will be good enough.

Yes but what evidence? We don't have any biomarkers that can be measured to determine the longevity effect of a particular intervention. For example if a hypothetical medication reduces blood glucose level (good) but also reduces skeletal muscle mass (bad) will that have an overall positive or negative effect on longevity? Who knows? It's a complex multifactorial issue.

Disc drives are much simpler. We have decades of data on failure rates.

I would say that the simplicity has to do with the linear nature of most failure modes of disk drives. The overall failure curve is nonlinear due to compounding per time probabilities. But those probabilities are only nonlinear/cross-interacting at the point where the drive is already considered to be "a loss", and our engineering/maintenance strategies take advantage of this fact. We do not generally consider a human to be "a loss", if say, they start getting chronic back pain, which can start to precipitate other problems in a compounding fashion.

Not dogs but mice. Mice are members of the supraprimate superoder (the euarchonta). Dog are more distantly related to humans than are mice and they live much longer and they cannot be genetically engineered as easily. We have already established causality for aging in mice using classical genetic methods—down to the level of large chromosomal stretch that usually contain 10 to 200 candidate genes. But we do not yet know the causal single gene variants that modulate lifespan in mice but we are systematically getting closer.

Will these putative genes also modulate healthspan in humans? That is a reasonable presumption that will need to be tested, with the recognition that gene-by-environment interactions will be most important.

Mice are weird in ways that disqualify them for aging research, IMO. For example, they and rats have two insulins (no other species does). We already know the insulin/igf-1 axis is important for aging.

we could check those findings by replicating them in other related animals

>genes only propagate if selected for, and there’s no selective pressure for longevity after reproductive age.

Couldn’t older men who are still fertile have children that propagates these genes? Wouldn’t this also occur if someone doesn’t lose fertility and keeps having children?

> The notion that somehow aging is “special” and therefore shouldn’t be regulated like “normal” diseases is not convincing.

Is the fact that innovations have declined since more regulation convincing or making any research needing more barriers a good thing?

Whenever a rejuvenation/life extension biotech post gets made here I always want to plug Rejuvenation Tech. They’re a YC company working in this space :)

Naive Idea, but some mechanisms, like the testosterone-level in males, change with age. Why can't we, as a first step, just try to keep the levels fixed where we have a "reference level"?

I've been interested in this field long enough that I'm still plenty happy with the fact we now have a longevity biotech field, despite it's issues. :)

I agree with the author that longevity biotech is frequently tripping over itself with enthusiasm to bring interventions to market (or some variety of off-label use) well before they're on solid scientific ground. You don't see this in, e.g., cancer research- if a novel kind of anti-cancer drug tests well in mice, you (almost) never see a sudden cottage industry pop up around it the next week. Obviously part of the difference is that most of us aren't expecting to suffer from cancer in the immediate future, whereas everyone expects to age; aging research faces a lot of weird psychological pressures that most industries do not.

For all that, though, there are a lot of parts where I think this article is too skeptical. As someone who uses machine learning in (non-aging-related) biotech, the discussion of "garbage-in/garbage-out" put me in mind of "Yes We Have Noticed the Skulls" [0]; we're well aware that data quality coming out of molecular biology is a problem, and anyone working in the field could give you a long list of the kinds of biases, distortions, and gaps that are known to occur in their areas of interest [1]. Not all of the grand claims made about biotech AI/ML are taking this expertise into account, certainly, but certainly many of them are.

[0] https://slatestarcodex.com/2017/04/07/yes-we-have-noticed-th...

[1] The list, regardless of what variety of data it applies to, would always end with "sometimes something unknown happened and the data just turned out bad, oh well."

> and most notably the opening lecture from Charles Brenner had a great take-down on all of the reasons why longevity genes are unlikely to exist (TL/DR – genes only propagate if selected for, and there’s no selective pressure for longevity after reproductive age).

I mean, we don’t just drop dead the minute we pass reproductive age. One would expect there to be genes that affect aging (including past reproductive age), either due to different environments creating different selective pressures or just genetic drift or genes with an adaptive function for reproductive life having a side effect for post-reproductive life.

Consider particularly that women have a shorter reproductive window than men, but live longer on average.

One should consider that breakthroughs in longevity research would be disastrous for humanity. The first to benefit from it will be the super rich, and various dictators. Economic inequality will rise, Stalins, Maos, Kim Ir Sens will rule without end.

Death is a great equalizer, take it away and people would be split into two castes: immortal super rich, and their short-lived slaves.

Just like smartphones are only for the super-rich? Technology becomes affordable to all over time.

I for one cheer on the billionaires trying to extend their lives - it will benefit us all, and remove much disease & suffering from this planet.

With smartphones, the super rich so not have the incentive to block everyone else from having them. Extreme pongevity is a whole different deal: those at the top do not want to be replaced, and what better way to do that by making it harder to get on their level?

Also, take inheritance. Business shark accumulates a fortune, then leaves it to his less competent children, who waste it, giving others a chance. Imagine a world where sharks do not naturally die from old age and keep their fortunes in best shape over centuries?

Many (most?) of those original fortunes were amassed by giving large numbers of people small amounts of something they’d rather have than money. It’s not only that they’d keep their fortunes in shape (what you’re arguing is a negative), but that they’d have a longer period of time to create value (and capture some of it) in the world.

How you could stop the greed of someone wanting to sell those treatments to the mass market? I imagine Mark Cubin (or any other "shark" billionaire) would fucking love to be the first trillionaire or quadrillionaire by being the person who made accessible the treatments for aging. Cancer alone: the ego-boost and vast wealth for the person whose company/research helped "cure cancer" (hell, even just 1 type of cancer). these "sharks" would "chomp" at the opportunity I imagine.

There is a lot of fake science out there and that could be used to reduce the market success.

If you are a member of an inner circle of an immortal oligarchy that already controls the most important markets, selling such treatments would effectively erode your already enormous advantage and fuel the would be competitors.

How is that going to work though? We're likely way past the carrying capacity of the whole planet-wide mesh of habitats, even if we make some huge technological leaps to reduce our adverse impact on the biosphere – right now, the combined H. sapiens biomass is about ten times that of all other non-livestock mammals combined, and just the space we take up is driving lots of other species to extinction. Cure aging and this will grow ad infinitum and likely outpace anything we can do to lessen this. I don't see people stop having children, most people are incredibly strongly wired to want them, and they're pretty important to how all our societies function.

So either you keep this cure away from most, creating an impossibly dystopian society of immortal lords and mortal slaves, or hope for a miracle like a terraformed mars within a few generations, or things are bound to crash horribly at some point probably not too far off.

That's highly speculative. Look at other tech revolutions and advancements: It hasn't always gone that way. The smartphones, cars, and PCs of billionaires aren't much better than that of normal people.

Did you ever notice that older people tend to be conservative and against the newer trends? Same people are often in power, having spent a life to get to their high position. If not for the fact that they have to inevitably die at some point, being replaced by younger people with less conservative views, they would be able to propagate their state of society indefinitely. Imagine if jim crow era politicians were still around, would they allow a black president to be elected?

Short life span is generally a boon for species as it improves adaptability. Taken to the extreme, bacterias evolve and adapt to everything precisely because new generations replace the old ones. Increase the lifespan of the humans in charge, and you get a total social stagnation, because all places at the top are occupied and you can't wait for the current occupants to free them by dying.

I don't know, the Kim family of North Korea has been staying in power for quite a while now. And wealth is even easier to pass down.

I often hear people smugly tsk-tsk’ing those who buy lottery tickets as not understanding math. The anti-aging, longevity crew isn’t much different to me. Except I’m hopeful that most of the money wasted on this nonsense is coming from wishful billionaires and rich people.

I agree with this claim. After years of hoping a “good” bio company to invest in longevity I finally have hope again. Without shilling here, but if you like thinking and discussing longevity in a decentralized autonomous organization (DAO) manner, a web 3.0 organization, than surely check out vita dao (search on google or twitter). This is not a financial advice or what so ever, dyor for always.

It's no wonder that the field is populated by crackpots.

They are trying to solve a problem nobody is worried about and nobody has ever been worried about in the history of the human specie.

People who dedicate more than 5 minutes a day to the thought of living to 120 are the usual suspects: Bezos, Ellison, Thiel and so forth.

A reputable industry cannot emerge if you can count the potential clients on one hand.

Aubrey de Grey said in 2007 and earlier a lot of people alive then will live to be 1000.

It's a very catchy thought, but so were Theranos's blood tests. It's almost the perfect scam, way better than Theranos's...investors will all be dead before he's proven wrong.

(Cynical take)

Aubrey is going grey which would suggest to me if he is practising what he preaches, he's not mastered it yet. Maybe he needs to find out what this cancer drug is doing? https://www.theguardian.com/science/2017/jul/21/cancer-patie...

He also drinks alcohol, he likes a pint, so perhaps he doesn't know that alcohol dissolves fat soluble vitamins from the liver, which in excess can cause a vitamin A deficiency. What he has is he has done time like a prisoner at these things called university's which generally reward people for academic conformity, having a memory and being able to use logic to argue points when elephants in the room appear. I'm also remind big pharma sponsor uni's in a variety of legal but potentially ethically questionable ways.

Now it should be noted that scientists have known a purified diet shortens life span, so arguably diets which restrict your ability to eat a varied diet, like a shake of sorts, could be doing you more harm, than eating top quality food products and then adding some supplements on top, whilst trying to not over eat.

Anyway read what you like, this is just one of many amino acids and a right mix of opinion which sort of represents life and the medical experts in general. https://joshmitteldorf.scienceblog.com/2017/02/06/glycine-an... https://raypeatforum.com/community/threads/aging-in-human-mi... https://novoslabs.com/novos-anti-aging-longevity-supplement/... https://pubmed.ncbi.nlm.nih.gov/29136945/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/

There is loads to read up on Glycine too numerous to list here, and there are loads of mistakes in scientific studies which if you read enough you can start to spot.

But I will also put this up. https://en.wikipedia.org/wiki/Angus_Barbieri%27s_fast

He had the world record for fasting, there used to be a movement in the 50's in the US called the Hygienists (Herbert Shelton) which was about water only fasting.

Guinness make a good point about unsafe practices, you dont want to deplete your body of some things like Glutathione when fasting, which is something the Hygienists never considered and possibly didnt know back then either. http://loveandtruth.net/shelton-fasting.html

Other factors with water only fasting and Ketogenic diets is Ketoacidosis, too many ketones and the liver cant handle the increase in acetone, you know nail polish remover! LOL

This probably sums up our medical knowledge best, the graph in the top left of this link. https://pubmed.ncbi.nlm.nih.gov/?term=glycine&sort=date&ac=y...

An explosion of knowledge where perhaps AI and big data can spot things the existing experts have missed? Like where AI can spot the subconscious bias in judges presiding over parole board requests.

Other points include, what is being taught is not always up to date, who sets the course work and writes the books and some knowledge being practiced is decades out of date and is likely contributing to worse outcomes.

Supermarkets also control the health of the nation because they tell farmers what properties they want in the food they sell, so supermarkets could tell pig farmers, they dont want pigs with a couple of inches of back fat, so the pig farmer goes to the nutritionist, can you reduce back fat, and the nutritionist comes back with a pellet mix which will achieve that objective. Farmer is happy, he is only interested in meeting the supermarkets requirements. He also doesnt know if this pellet mix is affecting the nations health or not.

So this lab grown meat will be interesting, it could end up "meating" the minimum legal standard to be called meat missing amino acids and other chemicals which can be found in the cheapest traditional reared meats, or it could become like a super meat containing everything we need that we can contribute to rude health if supermarkets didnt have profit margins to meat.

Anyway a contentious subject none the less and a very complex one.

> He also drinks alcohol, he likes a pint, so perhaps he doesn't know that alcohol dissolves fat soluble vitamins from the liver, which in excess can cause a vitamin A deficiency.

Funny enough, when I met him in person in 2007, he was drinking a beer and commented that "it's hardly immortalist".

Are you really saying no one has ever worried about death? I'm pretty sure everyone has, including you.

By the time it comes naturally, around 80 y/o 90 tops it would be a relief...you'd be so tired after a lifetime of fighting and you'd be such a second class citizen and excluded from all the fun and the social relevance that you'd be looking forward to checking out.

People who worry about death due to old age in their future are always the type who live in such luxury or are at their apex , having exhausted all other worries (and also wrongly project that they'll be in that frame of mind 50 or 60 years down the road).

> Including you

I have no interest in just existing, I want to thrive. Considering that pragmatically speaking it's not possible to thrive at 90, I have no interest in watching other people thrive, so checking out seems like a natural way of solving the issue.

> By the time it comes naturally, around 80 y/o 90 tops it would be a relief...you'd be so tired after a lifetime of fighting and you'd be such a second class citizen and excluded from all the fun and the social relevance that you'd be looking forward to checking out.

Does not match reality. Where are the waves of senior suicides?

> Where are the waves of senior suicides?

Where is their enthusiasm for life?

Of course survival instinct does its job very well. It even prevents people who are in extreme pain from committing the extreme act, but nonetheless it's not really that people look forward to stuff at 90.

And why would you? If you are not completely gone mentally, you can observe yourself losing relevance by the minute, younger guns attacking you and filling the void.

But curing aging / death would obviously make it so that you _can_ thrive at 90. Besides, most people I know who are in that age bracket are quite happy.

>People who worry about death due to old age in their future are always the type who live in such luxury or are at their apex

Not in my experience. I think people in general prefer existing over not existing, no matter what age.

> Not in my experience. I think people in general prefer existing over not existing, no matter what age.

Existing sucks, you want to thrive, meaning having fun, novelty, winning, and generally being a boss.

When you are old you simply don't thrive, you don't have fun, all the novelty is gone, you lose all the times, you lose your swagger because you become extremely risk averse both in your behavior in the natural environment as well as social behavior when around other people.

It is my sincere hope that anti-aging treatments never become viable. Successful longevity research will only lead the world to resemble Elysium, with two tiers of society: ultra-wealthy immortals and the impoverished, mortal, and expendable masses.

"Death by natural causes" (i.e., death linked to old age, as opposed to premature death due to murder, warfare, traumatic accidents, etc) deserves to be approached and treated with grace.

"Death by natural causes" induced by age include alzheimers, cancer, heart disease, strokes, etc. natural causes are just diseases that medicine isn't great at truly treating, often those diseases are exacerbated by age. I don't want to imply you are pro-cancer (for older individuals), but what "natural cause" deaths are unworthy of attention in your opinion?

Hey sorry for the delay in getting back. It's obviously a difficult line to draw because terminal diseases, especially those of the painful/slow degenerative type, are tragic and I would never wish them on anyone. I also understand that it will be a bitter pill for me to swallow were I to develop a terminal illness, and approaching death in that way is no doubt a very difficult.

To give you a specific sort of research that I feel is dangerous: preventing oxidative damage to telomeres (stopping one of the primary mechanisms of aging). Even though a breakthrough in that field will generate new therapies for schizophrenia and certain cancers, I believe that it will open a Pandora's box of externalities that, on balance, will outweigh the therapies.

I'm thinking about this more on principle: death is important for society in the same way that fire is important for a forest (imperfect analogy, but bear with me). The passing of older generations creates opportunities and mobility for younger generations, as well as room for cultural change that adapts with the rapid pace of technological change. I think in many ways the world would be a far worse place today were there large numbers of 120+ year-old people still around, voting however they would vote. Having a lot of 120-year-olds around would be ecologically untenable too.

In the original comment I refer to "grace", and by that I'm referring to the way that Randy Pausch or Morrie Schwartz describe their experiences with terminal disease. To them, death is an inevitability that highlights the value and sacredness of our short mortal lives. In the same way, I also really love the way how certain cultures treat funerals as celebrations of life rather than the somber sad traditions common in the West.

Put simply, death is what makes life valuable.

That's a somewhat pessimistic view, perhaps it will take humans who can live to be 150 or 200+ years to fully learn and understand complex matters.

I personally subscribe in part to Professor Bruce Ames Triage Theory http://www.bruceames.org/Triage.pdf TLDR, is when a limited amount of nutrition in ingested, the body triages the allocation of nutrition. Now some of this will be caused simply by chemical chain reactions that have developed due to evolution but there is also some element of control by the body simply because the body can control things like blood flow, so when exercising, less blood goes to the gut and in extreme, you will see some athletes experience diarrhoea when exercising.

A cancer study I read by a Swiss Uni used radioactive B12 for thyroid cancer because the thyroid takes up B12. Its radioactive so it can show up on the scanners and they found the B12 was distributed throughout the body, it did not exclusively go to the thyroid. So yes Professor Ames is correct with his theory but it is not applied to every part of the body, otherwise how do you explain the Sodium Potassium pump in cells which dumps nutrition out of the cells with too much sodium? https://en.wikipedia.org/wiki/Na+/K+-ATPase

There is a saying, "you are what you eat" which is largely true, and whilst legislation in some countrys prevent some supplements from being sold due to the fact they have a pharmacological effect on the body, there are also external factors at play as well, like the domestication of our food, pollution and modern day living in general.

Anyway you could argue we already have that Elysium two tier society right now, but I think its possible for most westerners to afford what's necessary to increase their lifespan substantially. Developing countries are a different thing. However your point about death by natural causes being treated with grace is important. Its quite likely many old people will be dying with a lifespan in their 70-100yr range, but people in their 40's or less could well if the right interventions were made, live to be 150+. That's because of things like the internet improving communication, silicon chip, improved manufacturing processes and the ability to use search engines to read the latest studies from any part of the world that have been published just last month! It seems like something out of science fiction, but increasing lifespans is just one of those things that could be happening right now.

It also increases other problems though, namely if everyone were to live a US lifestyle we need 4 planet earths, 2.5 planets for a UK lifestyle and 2 for a European lifestyle, so people like Elon Musk, Jeff Bezos and others trying to get into space more efficiently and explore is like the olde worlde sailing ships setting off to explore the unknown.

Whats sad is knowing your parents wont enjoy the rude health the younger generations could be enjoying and many will have struggled to bring you up even though their conditions were even better than those before them, but that is probably best summed up as human progress.

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