Japan’s anti-aging vaccine looks promising in mice(vstories.medium.com)
vstories.medium.com
Japan’s anti-aging vaccine looks promising in mice
https://vstories.medium.com/japans-anti-aging-vaccine-looks-promising-2d9b5e48ce56
122 comments
One thing I never understood is that if results in mice so often don’t carry over to humans, what about the opposite - treatments that might work for people but are discarded because they don’t work well with mice.
There are a lot of problems with medical testing, and much of it stems from simple ethics. It would be more effective to test on humans directly and who knows what amazing treatments we might find that don't work in rats. And yet.. that's hopelessly unethical.
It reminds me of a scene from House MD; >People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children.
Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
It reminds me of a scene from House MD; >People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children.
Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
Exactly. Last group of researchers that tested directly on humans happened to work for a certain political party that unfortunately managed to dominate Germany around the 1930-1940's.
Their "testers" happened to be people unjustly persecuted by their bosses, ranging from children to women and elderly.
Their "testers" happened to be people unjustly persecuted by their bosses, ranging from children to women and elderly.
They weren't the last group, they (along with Unit 731[1][2]) were just the most utterly and unashamedly barbaric group of savages to have done so.
Other groups of people have done plenty of unethical medical experiments since then - also typically against marginalized people.
Take https://en.wikipedia.org/wiki/Chester_M._Southam, for instance - thanks to his contributions to the study of cancer (consisting of injecting cancer cells into people without their consent). Thanks to his, uh, contributions to the field, he was later elected president of the American Association for Cancer Research.
[1] Which is utter nightmare fuel.
[2] Most of the members of which were given immunity from war crimes prosecution by the United States. Utterly mind-blowing. The ones that the communists were fortunate enough to get their hands on were subjected to a helping of Soviet justice.
Other groups of people have done plenty of unethical medical experiments since then - also typically against marginalized people.
Take https://en.wikipedia.org/wiki/Chester_M._Southam, for instance - thanks to his contributions to the study of cancer (consisting of injecting cancer cells into people without their consent). Thanks to his, uh, contributions to the field, he was later elected president of the American Association for Cancer Research.
[1] Which is utter nightmare fuel.
[2] Most of the members of which were given immunity from war crimes prosecution by the United States. Utterly mind-blowing. The ones that the communists were fortunate enough to get their hands on were subjected to a helping of Soviet justice.
I did work on medical devices and we did test on humans for non-life threatening conditions. The treatment wasn't that invasive though and it would never have had too bad side effects, the risk could be sufficiently reduced and the suffering of patients was greater than what the therapy could inflict.
Personally I wouldn't advertise any patriotism here, it is very important not to take advantage of desperate people here as long as the experimental treatment cannot possibly help against their conditions. Otherwise you certainly would loose more than you would gain. I doubt there can be a general rule though, the right choice depends on the circumstances and the risk to the patient.
Personally I wouldn't advertise any patriotism here, it is very important not to take advantage of desperate people here as long as the experimental treatment cannot possibly help against their conditions. Otherwise you certainly would loose more than you would gain. I doubt there can be a general rule though, the right choice depends on the circumstances and the risk to the patient.
> Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
It’s clear to me that modeling the human body would be complicated, but I don’t have any idea about the order of magnitude. Can someone chime in?
It’s clear to me that modeling the human body would be complicated, but I don’t have any idea about the order of magnitude. Can someone chime in?
I guess the most difficult part is modeling all possible interactions related to an infinity of chemicals, DNA variations, environment influences, past medical issues, etc, etc.
I bet this would require computational power equivalent to whatever is "processing" the govern of real-world interactions in our bodies.
I bet this would require computational power equivalent to whatever is "processing" the govern of real-world interactions in our bodies.
Well, to model organic interactions you basically need a molecule-level model of the body or even deeper - especially for extremely complex molecules like proteins (which can famously "fold" in extremely hard to predict ways).
So, to very accurately model the human body, you need a model that has as many parameters as there are molecules in a human body, give or take a few orders of magnitude.
I have no idea to what extent you could get away with more high-level models - i would expect they could work well for some kinds of problems, but not for very systemic interactions, like hormonal or aging-related issues, that affect each cell in the human body to some extent.
So, to very accurately model the human body, you need a model that has as many parameters as there are molecules in a human body, give or take a few orders of magnitude.
I have no idea to what extent you could get away with more high-level models - i would expect they could work well for some kinds of problems, but not for very systemic interactions, like hormonal or aging-related issues, that affect each cell in the human body to some extent.
I really doubt you'd start with "Let's emulate every atom of the human body". That's a huge waste of time. The atoms in my toenail are not relevant to most models you'd care about.
You'd probably start off instead by emulating specific proteins. That's already really hard, but obviously a trillion times easier than what you're suggesting.
Once you can emulate a number of proteins you can start to emulate interactions of drugs with those proteins. That's probably going to get you to a good enough heuristic where you can say "ok let's try this on something alive" or "this clearly doesn't work".
This is, to my knowledge, the existing approach being taken. It's just that a single protein is extremely complex. A single protein is a series of amino acids linked by peptides - each amino acid is itself a pairing of numerous atoms.
As you go from atom -> amino acid -> poly peptide -> protein you get a massive increase in complexity.
You'd probably start off instead by emulating specific proteins. That's already really hard, but obviously a trillion times easier than what you're suggesting.
Once you can emulate a number of proteins you can start to emulate interactions of drugs with those proteins. That's probably going to get you to a good enough heuristic where you can say "ok let's try this on something alive" or "this clearly doesn't work".
This is, to my knowledge, the existing approach being taken. It's just that a single protein is extremely complex. A single protein is a series of amino acids linked by peptides - each amino acid is itself a pairing of numerous atoms.
As you go from atom -> amino acid -> poly peptide -> protein you get a massive increase in complexity.
I thought the question was about developing new drugs entirely using computer models, at least until the first human trials. If that is the goal, we would need a model of the proteins in the entire body to get an idea of how a substance could affect every protein they interact with in every organ they reach, what organs it could actually reach, and how the modifications to each protein would in turn cascade.
And the toe nails and similar things are why I was saying "give or take a few orders of magnitude". Not to mention, certain drugs could affect your toenail.
And the toe nails and similar things are why I was saying "give or take a few orders of magnitude". Not to mention, certain drugs could affect your toenail.
I still think it would be unnecessary to do anything more than what I described, but just at a larger scale. But not the scale of emulating a whole human being. For the most part you're going to be looking for "does this bind with X but not Y" and expanding your set of X and Y is what makes things safer.
I think you could get to human trials using just a computer if you had a sufficiently sized set of emulated X's and Y's.
I think you could get to human trials using just a computer if you had a sufficiently sized set of emulated X's and Y's.
Well, if it binds with X, what prevents X+substance from binding with Y or Z?
Yeah you might want to add a few levels there for sure. But that's still a far cry from fully emulating the human body.
Actually, as far as we know, you need to add just as many levels as there are different substances in the human body. Not to mention, things could form structures that are problematic from a mechanical point of view, not just chemical. For example, gout is caused by crystalline formations causing damage to articulations. If you had crysatline formations like those in the stomach or other cavernous or muscular organ, you might have no problem. But, in any bony organ they are extremely problematic. Similarly for sand in the kidneys vs intestines and many others.
The body is much more complex than a collection of proteins.
The body is much more complex than a collection of proteins.
Am I the only one that sees the beauty and simplicity of a world that allows drug research companies to pay giant piles of money to people for them to agree to be test subjects for new treatments? The equalizing effect this could potentially have over wealth inequality across generations is arguably staggering. Some days it feels like our nobility and pride and respect for life are just ideals we claim on paper but end up just being huge shackles that keep us from preventing suffering in the now. We allow huge amounts of actual suffering and denigration of life to happen right under our noses.
Your imagination has veered into the entirely wrong direction.
If such a thing were legal, human test subjects would be the lowest classes, who would accept a pittance to support their family, or worse, who would sell their children for drug testing to score another hit. The vast majority of early drug trials cause extreme harm, so in essence any such contract would be a game of Russian roulette, except bullets to the head are a quick death. The extremely powerful incentive for companies would be to misrepresentat the risks and pay a pittance for the earliest trials, since these are the least likely to lead to profitable new medications.
Not to mention, if we were to replace mouse models with human subjects, the cost to develop new drugs would skyrocket, as even the least pittance afforded to some slave laborer in the this world would be more expensive than a mouse.
If such a thing were legal, human test subjects would be the lowest classes, who would accept a pittance to support their family, or worse, who would sell their children for drug testing to score another hit. The vast majority of early drug trials cause extreme harm, so in essence any such contract would be a game of Russian roulette, except bullets to the head are a quick death. The extremely powerful incentive for companies would be to misrepresentat the risks and pay a pittance for the earliest trials, since these are the least likely to lead to profitable new medications.
Not to mention, if we were to replace mouse models with human subjects, the cost to develop new drugs would skyrocket, as even the least pittance afforded to some slave laborer in the this world would be more expensive than a mouse.
I share your concerns about it, and there is definitely potential for it to be abused and for it to create an underclass. But even for those, why not at least explore the option and at the same time use regulation to make it safe and not open for abuse? We're perfectly fine doing all sorts of games of wack-a-mole with other areas that we're trying to regulate but the free-market is constantly working around, so why not here too?
But this is what we've done, right? Drugs are tested on people, but only after they've been proven to be (a) somewhat promising and (b) somewhat safe in animal models. This helps make human trials safe.
Secondly, we've removed the profit motive, so that people are not allowed to be coerced by money into trying out someone's drug, and drug companies are not incentivised to test their drugs exclusively on the poorest people - this helps prevent abuse.
Secondly, we've removed the profit motive, so that people are not allowed to be coerced by money into trying out someone's drug, and drug companies are not incentivised to test their drugs exclusively on the poorest people - this helps prevent abuse.
Unfortunately when money is an incentive, and money is also a requirement for life, you're not far from threatening to kill people if they don't take your experimental drugs. This is already an ethical concern with human drug testing.
Also, one benefit of mice is, morbidly, that you can immediately kill and autopsy them after treatment. I hope we can all agree that this would probably not be the right call for humans.
Also, one benefit of mice is, morbidly, that you can immediately kill and autopsy them after treatment. I hope we can all agree that this would probably not be the right call for humans.
Tally up another reason for UBI, where such undertaking will now be for voluntary luxury rather than survival desperation.
You are sadly not the only one, but this could only be ethical in a completely affluent society.
Simplicity can be elegant, but it can also be foolish. As a mechanism to combat wealth inequality the term foolish is probably even a bit euphemistic.
Simplicity can be elegant, but it can also be foolish. As a mechanism to combat wealth inequality the term foolish is probably even a bit euphemistic.
This probably happens. We're searching for drugs that "help humans, and don't kill them". And limiting our search to "helps mice, and doesn't kill them" is much more viable than trying random drugs on people and seeing how they do.
At least in this case, maybe as legislators get older they'll become more friendly to the idea.
They could go along the route of mRNA vaccines. Experimental granted for "emergency use". The rich and powerful will do that. So I doubt it needs 10 years. If they do this altruistically for the masses, yeah 10 is a good number. Not so for the rich and powerful that wish to live immortally.
Now that we have precedent to fast-track vaccines based on impact of the thing they treat, maybe we can apply this to aging which kills more people per year than pre-vaccine COVID did.
Haha..
Why test when we can fast-track and test on live people!
Great analogy and made me laugh ;)
Fast-tracking still involves testing. In the case of the coronavirus vaccine trials, most of them anyway, they went through all the same trials stages any other vaccine would go through. It just happened at a much accelerated tempo, with weeks between trials stages instead of many months or years. Volunteers, trials teams and vaccine stocks for the next stage were already recruited and commissioned before the completion of previous stages anticipating a green light to avoid any delays. There was still time to pull the plug at any stage though, if adverse results had been detected, as did actually happen to several candidate vaccines.
The results have been an astounding success, with vaccines that are about as safe and effective as those from previous development processes. So it is possible to safely fast track these projects with enough urgency and investment.
The results have been an astounding success, with vaccines that are about as safe and effective as those from previous development processes. So it is possible to safely fast track these projects with enough urgency and investment.
As you say, urgency and investment are key, and neither necessarily applies (or is worth applying) to the general case of medical research (in the absence of a once-in-a-century global urgent surge in demand for a particular slice of medical research). More specifically, it seems like much of this fast-tracking is due to:
a) the manufacturers being incentivized to dedicate resources to branch prediction, essentially making the failure path more expensive. and
b) the regulator expediting the bureaucracy for a specific set of approvals (essentially jumping the line). Presumably there are other applications that were delayed to support the expedited applications, and I'll bet the expediting process hurt overall bureaucratic efficiency.
For A, I'd assume that the option was already priced in by the pharma co's and is (in the non-urgent case) not particularly cost-effective. For B, I'm all for making bureaucratic systems operate more efficiently and responsively, but I'm not convinced that most circumstances are urgent enough to sacrifice throughput to the latency gods.
a) the manufacturers being incentivized to dedicate resources to branch prediction, essentially making the failure path more expensive. and
b) the regulator expediting the bureaucracy for a specific set of approvals (essentially jumping the line). Presumably there are other applications that were delayed to support the expedited applications, and I'll bet the expediting process hurt overall bureaucratic efficiency.
For A, I'd assume that the option was already priced in by the pharma co's and is (in the non-urgent case) not particularly cost-effective. For B, I'm all for making bureaucratic systems operate more efficiently and responsively, but I'm not convinced that most circumstances are urgent enough to sacrifice throughput to the latency gods.
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> The biggest problem is that mice are not humans, and as far as animal models go, they're not even a good one.
A model != an animal. A model is an animal + process for giving the animal a disease.
Mice can be a very good model. As a model for obesity drugs that work through appetite reduction most mouse models are great.
For Alzheimer's all models are terrible (amyloid beta injection, genetic over expression of tau, etc).
"Mice models are bad" sounds profound but doesn't really say anything. Far more informative to say "mouse models of senolytics are bad, and have poor translation to human trials." But we don't know this because we haven't really tried senolytics in humans, so we have no idea if mice are a good or bad model of human senolytics.
I'm idealistic because "mouse gets old and blood vessels don't work as well" is probably pretty similar to "person gets old and blood vessels don't work as well". As opposed to ALS, Alzheimer's, and Parkinson's which mice don't get so we just inject them with stuff we find in the blood and brain of the afflicted.
A model != an animal. A model is an animal + process for giving the animal a disease.
Mice can be a very good model. As a model for obesity drugs that work through appetite reduction most mouse models are great.
For Alzheimer's all models are terrible (amyloid beta injection, genetic over expression of tau, etc).
"Mice models are bad" sounds profound but doesn't really say anything. Far more informative to say "mouse models of senolytics are bad, and have poor translation to human trials." But we don't know this because we haven't really tried senolytics in humans, so we have no idea if mice are a good or bad model of human senolytics.
I'm idealistic because "mouse gets old and blood vessels don't work as well" is probably pretty similar to "person gets old and blood vessels don't work as well". As opposed to ALS, Alzheimer's, and Parkinson's which mice don't get so we just inject them with stuff we find in the blood and brain of the afflicted.
> Results in mice will probably not track to humans,
In this case I don't know if that's true. Total layman, but this sounds like autophagy triggered through an immune response. Autophagy is already promising fro human life extension. This feels like an approach that could be generalizable, even if perhaps the specific antibody might not apply.
In this case I don't know if that's true. Total layman, but this sounds like autophagy triggered through an immune response. Autophagy is already promising fro human life extension. This feels like an approach that could be generalizable, even if perhaps the specific antibody might not apply.
There have been a few past studies on senescent cells with quercetin, both alone and combined with other "senolytics" that have been encouraging.
A vaccine would be ideal, but senolytic supplements are likely closer.
https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...
A vaccine would be ideal, but senolytic supplements are likely closer.
https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...
Basically, they created anti-aging vac for mice. Human-wise remain to be seen. We are creating a super mice species. Better pray they don't screw up and release this to the wild. I already have hard time containing cockroaches and ants in my home. I don't want to add mice (or woest rats) to that list.
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Can anyone with a scientific background chime in on why this is nonsense that will never come to viability?
Reading the abstract for the paper (thanks to skybrian for providing the link) it seems that the phrase "anti-aging vaccine" is a gross exaggeration in this context rather than the science itself being flawed.
Broadly, the abstract seems to be describing a particular cell-surface marker found to be associated with senescence ("seno-antigen") which can be targeted by a therapy ("genetic ablation") which accelerates removal of cells with that marker. Doing so improves the lifespan of mice so treated.
Thus, as the abstract concludes, "...vaccination targeting seno-antigens could be a potential strategy for new senolytic therapies."
Broadly, the abstract seems to be describing a particular cell-surface marker found to be associated with senescence ("seno-antigen") which can be targeted by a therapy ("genetic ablation") which accelerates removal of cells with that marker. Doing so improves the lifespan of mice so treated.
Thus, as the abstract concludes, "...vaccination targeting seno-antigens could be a potential strategy for new senolytic therapies."
It's very hard to critique an article that has the quality of GPT-3 generated blogspam and doesn't contain a link to better sources.
I take offense at your implication that GPT3 generates poor quality articles.
I usually look to r/science for this sort of skepticism. This particular thread doesn't seem especially negative...
https://www.reddit.com/r/science/comments/ren6cc/japanese_sc...
https://www.reddit.com/r/science/comments/ren6cc/japanese_sc...
Senescent cells are only one factor in aging. You've also other mitochondrial DNA damage, accumulating nuclear DNA damage leading to cancer, gunk building up inside lysosomes, gunk building up elsewhere, etc. If I were to try to rank them senescent cells would probably be second or third on the list. Potentially a really big deal but not at all synonymous with aging in general. That is, if this actually pans out.
Killing senescent cells is one thing.
Making sure they actually get replaced with new cells instead of scar tissue is another.
Until that’s resolved, killing the wrong kinds of senescent cells will kill you much faster than leaving them alone, so even highly targeted killing of senescent cells can’t “rejuvenate” all your organs.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)...
Making sure they actually get replaced with new cells instead of scar tissue is another.
Until that’s resolved, killing the wrong kinds of senescent cells will kill you much faster than leaving them alone, so even highly targeted killing of senescent cells can’t “rejuvenate” all your organs.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)...
Shouldn't science be the standard? Why implicitly be doubtful?
History?
Given N "advances" that you hear touted based on mouse trials, how many turn into real human therapies? (Curing aging in mice isn't really the advance we're looking for.) How many turn into real human therapies that live up to the breathless announcements that were made based on the mouse trials? I don't have hard evidence, but my gut estimate is 10-20% actually deliver.
So, yes, while waiting for the science, there is some empirical grounds to have a default stance of doubt (or, if you prefer, skepticism).
Given N "advances" that you hear touted based on mouse trials, how many turn into real human therapies? (Curing aging in mice isn't really the advance we're looking for.) How many turn into real human therapies that live up to the breathless announcements that were made based on the mouse trials? I don't have hard evidence, but my gut estimate is 10-20% actually deliver.
So, yes, while waiting for the science, there is some empirical grounds to have a default stance of doubt (or, if you prefer, skepticism).
1) The original linked article is not a link to a scientific work. Therefore it's credence should be taken with a grain of salt as news articles need clicks more than they need boring sounding article titles.
2) In science often abstracts or intros open with grand ideas before settling into a much smaller scope.
3) The rise of predatory journals, not to mention people citing pre-print arXivs means even if something looks likes a reasonable article, it's good to get the opinions of other experts.
4) Just because something works doesn't imply how practical it is for actual deployment. (I've been to plenty of chemical talks about fantastic polymers, I've only ever seen one turn into anything of value.)
2) In science often abstracts or intros open with grand ideas before settling into a much smaller scope.
3) The rise of predatory journals, not to mention people citing pre-print arXivs means even if something looks likes a reasonable article, it's good to get the opinions of other experts.
4) Just because something works doesn't imply how practical it is for actual deployment. (I've been to plenty of chemical talks about fantastic polymers, I've only ever seen one turn into anything of value.)
varelse(2)
Paper is here: https://www.nature.com/articles/s43587-021-00151-2
Came to comments to share this, thanks.
Relevant XKCD: https://xkcd.com/882/
Relevant XKCD: https://xkcd.com/882/
Posting that comic without any particular context seems distracting. Do you see any evidence that the authors paid no attention to FPR corrections?
Posting xkcd is the smart persons equivalent of reaction GIFs.
It seems odd this is perceived as anti-aging rather than removing "zombie" cells from our body as a preventative measure that could be turned against us.
This wouldn't stop the cell from "aging" and we still have aging-related issues like with memory degradation and other stuff that is not related to the zombie cells.
This wouldn't stop the cell from "aging" and we still have aging-related issues like with memory degradation and other stuff that is not related to the zombie cells.
Rebranding it an anti-zombie vaccine would be metal.
What kind of metal? Zinc? Nickel? Hassium?
"Yeah, stopped by for my Anti-Zombie booster shot at CVS on the way home today, feeling a little ill but looking forward to surviving the apocalypse. How was your day?"
“Sponsored by Monster Energy Drinks”
To put it another way, this won't extend the Hayflick limit [1], so your cells will still die after the same number of divisions.
1. https://en.wikipedia.org/wiki/Hayflick_limit
1. https://en.wikipedia.org/wiki/Hayflick_limit
I'm worried we're going to find an epigenetic time bomb in destroying all senescent cells. These cells aren't just old, they remember our old life. Some adaptations to past trauma save us from further trauma. Others are more maladaptive.
If this vaccine causes the immune system to 'forget' by killing off B cells, then you may have to get a booster shot for every vaccine you've ever had. That may not sound like a big deal but that creates a class division for longevity treatments. I could afford to take a month off, quarantine myself and get twenty booster shots. Some of my neighbors can't, so either they risk getting sick or they don't take the treatment at all.
Science fiction has always asserted there would be class divisions in these sorts of treatments, so perhaps that's not a surprise.
If this vaccine causes the immune system to 'forget' by killing off B cells, then you may have to get a booster shot for every vaccine you've ever had. That may not sound like a big deal but that creates a class division for longevity treatments. I could afford to take a month off, quarantine myself and get twenty booster shots. Some of my neighbors can't, so either they risk getting sick or they don't take the treatment at all.
Science fiction has always asserted there would be class divisions in these sorts of treatments, so perhaps that's not a surprise.
This is a little extreme. When was the last time you had to take a month off for a flu shot? Adults do this all the time when traveling overseas.
It may be inconvenient to take a half day off to go to the clinic, but what you are saying is extreme.
Not to mention, people take time off for augmentations and plastic surgery all the time.
Not to mention, people take time off for augmentations and plastic surgery all the time.
> When was the last time you had to take a month off for a flu shot?
A flu shot? No. If you are traveling internationally they recommend getting your vaccinations a month in advance. Plus it's generally not the case that they want you to take every vaccination on the same day. If you had to be re vaccinated for everything you're currently required to go to school, you'd be taking DTap, Polio, Varicella, MMR, Hep A, Hep B, Hib, and probably Meningitis, and a couple of those take multiple doses.
> Not to mention, people take time off for augmentations and plastic surgery all the time.
Everyone, or upper and middle class?
A flu shot? No. If you are traveling internationally they recommend getting your vaccinations a month in advance. Plus it's generally not the case that they want you to take every vaccination on the same day. If you had to be re vaccinated for everything you're currently required to go to school, you'd be taking DTap, Polio, Varicella, MMR, Hep A, Hep B, Hib, and probably Meningitis, and a couple of those take multiple doses.
> Not to mention, people take time off for augmentations and plastic surgery all the time.
Everyone, or upper and middle class?
If a B cell becomes senescent it isn't going to be contributing contributing to your immune response in any event. In general a senescent cell represents a cell that failed at apoptosis when it was supposed to kill itself, going in and having the immune system finish the job won't hurt anything. That is, assuming that the vaccine works in humans and doesn't have unwanted side effects, which is very much a possibility at this stage.
I think that depends on utility. If the senescent cells are functionally useless, then culling them should have few consequences (although your liver and kidneys might object to having that many cells being cleaned up at once). But if they are still sort of functioning in their primary or secondary functions (eg, structural integrity) then disappearing them all at once becomes a problem.
It's true that suddenly having a whole bunch of senescent cells killed at once could cause big problems. But the number of cells that become senescent is a small fraction of the cells that manage to off themselves the way evolution intended. If this is a problem it's a problem we're continually enduring and which won't be much worsened by the drug.
When you’re 11 this is true but the whole idea with this theory of aging is that the old cells pile up, and getting some cell division rejuvenates the tissues. Cell division is controlled by feedback mechanisms based in part on intracellular pressures. That’s how your finger knows to fill in a cut. Lose some tissue, trigger division.
So if you’re a tech billionaire who has noticed laugh or worry lines while checking out your hair transplants in the mirror, your body is already full of targets for this treatment. And the treatment is a vaccine. You can’t titrate a vaccine the way you can an SSRI, ramping up slowly to a full dose. Or none that I know of, so your whole body is going to be devouring itself many times faster than it normally does. You will probably develop a fever and feel weird for a moment, and your disposal systems for spare materials might be overwhelmed, like with rhabdo (mass muscle cell death leading to protein poisoning and kidney failure).
I wonder if this is a case where antibodies should be administered intravenously over the course of days followed by the vaccine to make it permanent if your body handles it well.
So if you’re a tech billionaire who has noticed laugh or worry lines while checking out your hair transplants in the mirror, your body is already full of targets for this treatment. And the treatment is a vaccine. You can’t titrate a vaccine the way you can an SSRI, ramping up slowly to a full dose. Or none that I know of, so your whole body is going to be devouring itself many times faster than it normally does. You will probably develop a fever and feel weird for a moment, and your disposal systems for spare materials might be overwhelmed, like with rhabdo (mass muscle cell death leading to protein poisoning and kidney failure).
I wonder if this is a case where antibodies should be administered intravenously over the course of days followed by the vaccine to make it permanent if your body handles it well.
Before an epigenetic time bomb detonates it's likely you will get your own very personalized cancer that will take you out unless we have come up with a universal cure-all for it. We could probably do that in a decade or two now but it would require concentrated effort. And the same mRNA technology behind the Moderna and the Pfizer vaccines might be the basis of a first generation treatment. But also it won't be cheap. At least initially. So either you'll have to have the money up front or you'll have to make a deal with someone who does and I doubt the latter ends well.
> it's likely you will get your own very personalized cancer that will take you out
Do you mean because of the longevity treatment, or in the sense that everyone gets cancer if they live long enough?
Do you mean because of the longevity treatment, or in the sense that everyone gets cancer if they live long enough?
Everyone gets cancer if they live long enough. And cancer is subject to evolution in your own body as well as it personalizes itself to evade your immune system.
It's why you can extend your lifespan but you will ultimately be foiled unless you solve the problem holistically.
It's why you can extend your lifespan but you will ultimately be foiled unless you solve the problem holistically.
> Everyone gets cancer if they live long enough.
Every human. Not all mammals get cancer though. Whales live a very, very long time, and to my knowledge there's no incidence of cancer. In general (and somewhat paradoxically) the larger the animal the less likely they are to get cancer.
Every human. Not all mammals get cancer though. Whales live a very, very long time, and to my knowledge there's no incidence of cancer. In general (and somewhat paradoxically) the larger the animal the less likely they are to get cancer.
One of the biggest risk factors for cancer is age. If you can slow down aging you can reduce cancer risks considerably.
Your body produces cancerous cells all the time, but most of the time the immune system finds them. But when your immune system gets old and sluggish it doesn't find and kill them as well increasing risks of cancer. So if we can figure out how to keep your immune system young we could reduce risks of cancer by 20-100x.
Your body produces cancerous cells all the time, but most of the time the immune system finds them. But when your immune system gets old and sluggish it doesn't find and kill them as well increasing risks of cancer. So if we can figure out how to keep your immune system young we could reduce risks of cancer by 20-100x.
It seems to me than 'longevity treatments' are likely to be a quality of life situation over a quantity of life cure, changing the curve more than the intercept.
A higher quality middle age has quality of life benefits that probably stand on their own, but remaining active also does increase life expectancy dramatically. So the cause-effect curve may be treatment->healthy lifestyle->life expectancy, instead of treatment->life expectancy.
I could get the jab, continue to be a couch potato, and leave a prettier corpse.
A higher quality middle age has quality of life benefits that probably stand on their own, but remaining active also does increase life expectancy dramatically. So the cause-effect curve may be treatment->healthy lifestyle->life expectancy, instead of treatment->life expectancy.
I could get the jab, continue to be a couch potato, and leave a prettier corpse.
I'm intensely active and my body is great for now. But it's not going to be great forever. And I could probably afford longevity treatments to add a decade or two. But I'm disinclined to do so right now if things keep proceeding downward. Yet I will never be a couch potato. I watch less than 4 or so hours of TV weekly in an age when most watch 8 hours daily.
"aging" is a complex set of a number of different issues. Cell senescence is generally considered to be an age related issue.
Fisetin does the same thing.
In mice.
Ok, we've inmiced the title above. Thanks!
The contention that mice are the most intelligent beings on the planet seems more plausible every year.
They certainly coopted humans to solve all their problems
If it was in humans you wouldn't read about it anywhere
So is this a similar anti-aging mechanism to autophagy triggered by fasting?
That's what it sounds like to me as well.
Anti-aging is an economics problem more than a medical one. If you radically extend lifetimes, those who have been alive the longest have had the most time accumulate capital. There's very little chance for someone 200-300 years younger to have any way to match the economic means of their seniors, resulting in a highly destabilizing permanent economic hierarchy.
If you think gen z are pissed at boomers, slip another 200 years of differential in and things start to look really bad.
If you think gen z are pissed at boomers, slip another 200 years of differential in and things start to look really bad.
I wouldn't say it's more of an economics problem...it's still a medical impossibility as far as we know.
Everyone develops cancer given a long enough timeline. If we can somehow defeat that, or give everyone robot bodies after their biological one fails, we still have a wide array of brain diseases to defeat.
Everyone develops cancer given a long enough timeline. If we can somehow defeat that, or give everyone robot bodies after their biological one fails, we still have a wide array of brain diseases to defeat.
fwiw, robot body with human brain would almost certainly be severely immunocompromised. Organs are important.
I do believe that economics itself will take into account increased lifespans, UBI and other measures of normality...
Here's a take, if people get to live so much longer, then money is not the variable to be optimised for humanity in general...
Also, rates of labour, skill, energy expenditure and so many variables will undergo a change in definitions.
I would like to see everyone make it... I believe so would everyone else, if increased lifespans are on the line.
Here's a take, if people get to live so much longer, then money is not the variable to be optimised for humanity in general...
Also, rates of labour, skill, energy expenditure and so many variables will undergo a change in definitions.
I would like to see everyone make it... I believe so would everyone else, if increased lifespans are on the line.
economy is downstream from technology, economy adapts
But more importanly, this isn't necessarily about extending lifetimes but making them worth it (and possibly productive until the last minute)
But more importanly, this isn't necessarily about extending lifetimes but making them worth it (and possibly productive until the last minute)
Yup, while societies do have momentous occasions of revolution, they are rather rare. It's more so people of a generation dying off allowing newer blood to come in. I have no doubt that societies would eventually stagnate if such anti-aging mechanisms become widely available enough. And they will only be available to the rich and in-power at first, mind you.
I'm annoyed to have been born early enough for biological life extension to not be available, but late enough to actually consider it a possibility.
I'm still hopeful. There's quite a lot of promising research being done right now, with huge amounts of money being poured into it. Latest papers point to aging being an intentional, programmed, self-sustaining process, that is the continuation of the organism's development which just happens to become destructive around 25 years of age (in humans). The older theory that aging is due to accumulated damage and telomere attrition is mostly getting abandoned.
The process of aging, as it turns out, is malleable. It's most probably controlled by some signaling molecules in the bloodstream, it's just that we don't know yet which ones. Look up "heterochronic parabiosis" for related research.
Then there are Yamanaka factors, those not only erase cell identity, they also erase the age. Of course you don't want all your cells turning into stem cells, but the fact that this mechanism exists at all means that it's likely possible to isolate the pathway that resets the age of a cell but keeps the identity.
Then there's the "rejuvenation event" during embryonic development shortly after conception, as shown by DNA methylation clocks.
So currently we have these puzzle pieces that we don't yet know how to put together, and some are still missing. We'll get there eventually.
It's not even going to be life extension, as in, "you'll still get old and eventually die of old age but slower", it's full-on rejuvenation, as in, "you'll look and feel 25 and the only thing giving away your actual age will be your ID".
The process of aging, as it turns out, is malleable. It's most probably controlled by some signaling molecules in the bloodstream, it's just that we don't know yet which ones. Look up "heterochronic parabiosis" for related research.
Then there are Yamanaka factors, those not only erase cell identity, they also erase the age. Of course you don't want all your cells turning into stem cells, but the fact that this mechanism exists at all means that it's likely possible to isolate the pathway that resets the age of a cell but keeps the identity.
Then there's the "rejuvenation event" during embryonic development shortly after conception, as shown by DNA methylation clocks.
So currently we have these puzzle pieces that we don't yet know how to put together, and some are still missing. We'll get there eventually.
It's not even going to be life extension, as in, "you'll still get old and eventually die of old age but slower", it's full-on rejuvenation, as in, "you'll look and feel 25 and the only thing giving away your actual age will be your ID".
Not too late to improve your chances with great amounts of exercise, nutrition, and green tea, while minimizing calories.
I still have hopes. I don't think meaningful (decades-long) life extension will become reality before my time comes due, but maybe suspended animation can. We discussed isochoric freezing (for food preservation purposes) recently on HN. The concept can be used for tissue preservation as well [1], and at some point maybe for whole body preservation. One can dream ...
[1] https://www.nature.com/articles/s42003-021-02650-9
[1] https://www.nature.com/articles/s42003-021-02650-9
I'll bet you that this goes for everybody alive today. Wait, strike that ;)
What are you afraid of?
When the day comes that it becomes really real and everyone from now on gets to live for a few hundred years. But, not you. You are already too old for it to work. Maybe if you led a much more healthy lifestyle. But, no. You get to grow progressively more decrepit while watching people younger than you not go through the same problems. Eventually you will die of it while they are still partying hard in their 80s and will continue to do so for two hundred more years. Good for them. Sucks to be you.
> Eventually you will die of it while they are still partying hard in their 80s and will continue to do so for two hundred more years. Good for them. Sucks to be you.
yeah, but you don't have to spend centuries toiling away as a slave for the Immortal Dictator
yeah, but you don't have to spend centuries toiling away as a slave for the Immortal Dictator
I do wonder how an economic system would function if people worked for 50 years and then had 200+ years of retirement. Perhaps the production/consumption ratio will work out as automation/ai/robots increases labor productivity. Of course it’s wildly optimistic to hope for this outcome, and some sort of wage slave or indentured servitude arrangement is more likely for the masses.
Most people don't retire with any meaningful amount of savings. Presuming the government doesn't give you social security benefits if you're actually able bodied, you would just keep working and stay poor. The larger concern is compounding wealth inequality by the mega rich who never die and just continue to accumulate ownership of everything. And of course immortal dictators.
With meaningful life extension you'd have to increase the number of years people worked.
But most people would probably take the "you have to work an extra 100 years, but you get to live an extra 125" bargain.
But most people would probably take the "you have to work an extra 100 years, but you get to live an extra 125" bargain.
He prefers to be called President Bezos.
He said "annoyed" not "afraid".
'death' answering the question you mean; if not the one you asked.
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Great.
One step closer to raise our mice overlords.
One step closer to raise our mice overlords.
Seems odd to call this a "vaccine" isn't this more like "gene therapy"?
Do the Japanese need it? They have excellent genetics already
> Does it work? It does and it works quite well. Tests have shown that the preparation developed by the scientists forced the production of antibodies in the bodies of mice, which through the white blood cells attacked the aging cells in their bodies. The average lifespan of laboratory rodents that took the preparation extended by 15 percent relative to the control group, and individuals suffering from arterial stiffness saw a significant reduction in the damaged areas of these blood vessels.
Results in mice will probably not track to humans, assuming this treatment even makes it to that stage. The development time for most vaccines is on the order of 10 years or more, so even if it does make it (again, unlikely), it would be at least 10 years before this becomes available to humans. And there's a lot that can go wrong along the way. The biggest problem is that mice are not humans, and as far as animal models go, they're not even a good one.
Regarding that 15%, without some error bars (which can be quite large) it will be hard to say how "promising" this actually is.