Rapamycin: The unlucky history of an anti-aging drug(bigthink.com)
bigthink.com
Rapamycin: The unlucky history of an anti-aging drug
https://bigthink.com/health/unlucky-history-rapamycin-anti-aging/
185 comments
So in the science of fitness, there's a lot of woo, but there are a few really clear wins. One such example in weight lifting is supplementing creatine. It's well researched, fairly inexpensive, the performance improvements are significant and well documented, and it's very safe with side effects being mild and rare. Once you're actually doing the exercise and nutrition part more or less right, it's hard to argue against supplementing creatine. It's used by the vast majority of professional bodybuilders and most experienced weight lifters.
Is there anything similar in the science of anti-aging? Where (A) The body of research is large, well established, and mostly uncontroversial; (B) The benefits and safety profile are good; (C) The majority of people who are serious about this stuff use it/take it/do it.
Is there anything similar in the science of anti-aging? Where (A) The body of research is large, well established, and mostly uncontroversial; (B) The benefits and safety profile are good; (C) The majority of people who are serious about this stuff use it/take it/do it.
Metformin.
Research in humans suggests that metformin can impact mortality. A meta-analysis published in 2017 that included 53 different studies concluded that metformin reduces all-cause mortality and diseases of aging, independent of its effect on diabetes.
Also, combinations of Metformin, rapamycin and resveratrol, and NMNs.
Davis Sinclaire is probably the leading expert on those, now. He is professor of genetics at Harvard.
https://youtube.com/watch?v=bRWT7hVgwuM
Research in humans suggests that metformin can impact mortality. A meta-analysis published in 2017 that included 53 different studies concluded that metformin reduces all-cause mortality and diseases of aging, independent of its effect on diabetes.
Also, combinations of Metformin, rapamycin and resveratrol, and NMNs.
Davis Sinclaire is probably the leading expert on those, now. He is professor of genetics at Harvard.
https://youtube.com/watch?v=bRWT7hVgwuM
Worth pointing out that Metformin has a host of unpleasant and common side effects. E.g., here's 40% of type 2 diabetics not adhering to the prescribed dosing protocol: https://joppp.biomedcentral.com/articles/10.1186/s40545-022-...
> A number of studies assessing adherence to diabetes medications in patients with type 2 diabetes have reported that metformin has the lowest adherence rates when compared with other OAAs.
> A number of studies assessing adherence to diabetes medications in patients with type 2 diabetes have reported that metformin has the lowest adherence rates when compared with other OAAs.
Is it known what the mechanism is for metformin's effect on longevity?
If it's due to its ability to reduce blood glucose levels, then berberine may be another way to get a similar effect.
Berberine stimulates glucose transport through a mechanism distinct from insulin
https://www.sciencedirect.com/science/article/pii/S002604950...
Efficacy of Berberine in Patients with Type 2 Diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/
It also lowers cholesterol
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
https://www.nature.com/articles/nm1135
But pure berberine is not absorbed very well in the intestines, so you need to buy a good formation for it.
Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine
https://www.ncbi.nlm.nih.gov/pubmed/20237966/
Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
https://pubmed.ncbi.nlm.nih.gov/24607213/
The best thing might be to cook with barberries:
https://thecaspianchef.com/2020/01/18/zereshk-polo-saffron-b...
If it's due to its ability to reduce blood glucose levels, then berberine may be another way to get a similar effect.
Berberine stimulates glucose transport through a mechanism distinct from insulin
https://www.sciencedirect.com/science/article/pii/S002604950...
Efficacy of Berberine in Patients with Type 2 Diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/
It also lowers cholesterol
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
https://www.nature.com/articles/nm1135
But pure berberine is not absorbed very well in the intestines, so you need to buy a good formation for it.
Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine
https://www.ncbi.nlm.nih.gov/pubmed/20237966/
Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
https://pubmed.ncbi.nlm.nih.gov/24607213/
The best thing might be to cook with barberries:
https://thecaspianchef.com/2020/01/18/zereshk-polo-saffron-b...
This one is really interesting, thanks. I think it's the closest any mentioned substance comes to passing the "creatine test" (for whatever that test is worth; I just made it up).
(A) The body of research is, in general, large and uncontroversial.
(B) The safety profile is good. The benefits for diabetics are certainly large. Probably no drug has been studied for anti-aging effects as extensively as creatine has been for fitness applications, so I'm not sure anything can fulfill that criteria. But it seems like the present research on metformin supports a variety of positive effects for non-diabetics with more on the way.
(C) I wouldn't know whether the majority of people who are serious about anti-aging use it but it does get mentioned a lot.
Pretty positive endorsement overall!
(A) The body of research is, in general, large and uncontroversial.
(B) The safety profile is good. The benefits for diabetics are certainly large. Probably no drug has been studied for anti-aging effects as extensively as creatine has been for fitness applications, so I'm not sure anything can fulfill that criteria. But it seems like the present research on metformin supports a variety of positive effects for non-diabetics with more on the way.
(C) I wouldn't know whether the majority of people who are serious about anti-aging use it but it does get mentioned a lot.
Pretty positive endorsement overall!
It looks really promising. However, there are some growing concerns I believe that link it with mitochondrial dysfunction as well, if I recall correctly. Hopefully that's not the case, but it's a developing story. (It does reduce exercise output as well if someone is an athlete and cares about hat, but since it does mimic exercise in a way on a cellular level, that's to be expected I guess). :'(
There's always exceptions in popular medicine. No doubt a small minority of people get no benefit, or may even be mildly harmed by the medicine. But Metformin, in particular, is one of the most popular drugs in the world, and it's strong safety profile is well established. "All-cause mortality is lower in people on Metformin". So, I don't think there will be any big surprises found in its safety, but maybe we'll find that a certain minority of the population aren't suited for it.
Mitochondria need proper care too. I take iodine and magnesium for asthma (which is cured) and I hear iodine is also go for mitochondria, which might explain why it's good for so many things.
By far the most important thing in anti aging that checks all boxes is excercise and getting nutrition right (no excess fat).
Most of the interesting stuff happens when you focus on just A part: Yamanaka factors are both super powerful, established as reversing the probably most important hallmark of aging and super dangerous (causes cancer) at the same time.
What's promising is the pace of research: in 20 years there's a good chance to have real safe anti-aging available, but we still need to survive until then.
Most of the interesting stuff happens when you focus on just A part: Yamanaka factors are both super powerful, established as reversing the probably most important hallmark of aging and super dangerous (causes cancer) at the same time.
What's promising is the pace of research: in 20 years there's a good chance to have real safe anti-aging available, but we still need to survive until then.
> By far the most important thing in anti aging that checks all boxes is excercise and getting nutrition right (no excess fat).
Do you mean "don't eat excess fat" or "don't have excess fat on your body"? It's not clear to me from the context.
Do you mean "don't eat excess fat" or "don't have excess fat on your body"? It's not clear to me from the context.
Second probably.
Definately. The optimal body fat percantage is at about 12% for men and 15% for women, but I can't find a study that really tries to find that optimum.
There have been already studies showing that body fat percentage is a better predictor of mortality than BMI, but most studies focused on BMI in the past, as it's easier to measure.
There have been already studies showing that body fat percentage is a better predictor of mortality than BMI, but most studies focused on BMI in the past, as it's easier to measure.
I really appreciate this comment a lot. Feels like it hits the nail on the head.
I've seen some of the discussion about/around the Yamanaka factors and it feels like an anime plot point, honestly. I need to look more into them and understand them a bit better. They're the ones implicated in stem cells returning back to pluripotency, right (and then the long deep dive about DNA damage/repair/what the heck is happening in the disparity between repairing damage for reproduction vs the everyday repair, etc...)?
I've seen some of the discussion about/around the Yamanaka factors and it feels like an anime plot point, honestly. I need to look more into them and understand them a bit better. They're the ones implicated in stem cells returning back to pluripotency, right (and then the long deep dive about DNA damage/repair/what the heck is happening in the disparity between repairing damage for reproduction vs the everyday repair, etc...)?
You're half right, they are only resetting epigenetics (for example DNA methylation that is important in cell specialization), not DNA.
Altos Labs being funded is both a blessing and a curse, because it funded the best researchers in this area with hundreds of millions of dollars (5-10x their salary in what they were making as university professors), but since it was founded, there are much less publications available.
Altos Labs being funded is both a blessing and a curse, because it funded the best researchers in this area with hundreds of millions of dollars (5-10x their salary in what they were making as university professors), but since it was founded, there are much less publications available.
[deleted]
I think the important thing is to concentrate on the diet and exercise and not sit around living an unhealthy lifestyle and hoping to get on one of these drugs that is possibly not that great anyway or has some serious side effects you could end up with.
It's pretty obvious older people who have kept their fitness (cardio & strength, not just one of the two) up and their weight down their entire lives have profoundly higher quality of life.
That requires a totally different lifestyle from the standard "geek lifestyle" though.
It's pretty obvious older people who have kept their fitness (cardio & strength, not just one of the two) up and their weight down their entire lives have profoundly higher quality of life.
That requires a totally different lifestyle from the standard "geek lifestyle" though.
Very much so, I think it's about healthspan rather than lifespan for many people.
Hopefully we can improve that. Many people would be much more okay with feeling great up until an old age, have a few weeks of infirmity, and then pass away rather than the multiple decades of gradual decay that we have now.
Not that that's necessarily entirely realistic or possible, but it would be nice, if it is a possible thing indeedy.
Hopefully we can improve that. Many people would be much more okay with feeling great up until an old age, have a few weeks of infirmity, and then pass away rather than the multiple decades of gradual decay that we have now.
Not that that's necessarily entirely realistic or possible, but it would be nice, if it is a possible thing indeedy.
What's wrong with excess fat as opposed to excess calories in the form of other macronutrients?
its a little ambiguous but they might have meant body fat, not intake....
> By far the most important thing in anti aging that checks all boxes is excercise and getting nutrition right (no excess fat).
Nutrition is difficult to get right because of the contradictory and plain harmful information that we have been receiving for so long.
For example: is fruit juice "healthy"? Not really, when you consider that you are far more likely to consume way more fruit that you otherwise would, and a lot of fiber content is removed. We are unlikely to eat 10 oranges in a row, but that's easy in juice form. That's without extra sugar - if sugar is added, then it's just a soda with added nutrients. And the problem with that is that fructose is only metabolized by the liver (turning into triglycerides), with a mechanism that's comparable to the one used to metabolize alcohol.
We have been told that fat is bad. Due to consumer demand, the industry start removing fat content. But then things taste horrible, so the solution was to add sugar.
So now we are worse off: not only we are consuming a lot of sugar (75% of all products in the supermarket have sugar, including 'salty' ones), but we haven't even attacked the problem that prompted fat removal (increase in heart conditions) in the first place. Fructose in particular turns into triglycerides, and gets stored as fat(with uric acid as byproduct, with way more free radical formation than glucose, and it even uses up ATP). It didn't address the heart issue, and actually made it worse. People have become far more obese than when they ate fats, as fats (plus fiber) make you feel full for longer. It also screws up hunger hormones and sugar is addictive by itself.
Or let's take bread. White bread is starting to get considered harmful, but then the alternative that's pushed is whole bread. It matters very little. If that's all we ate, we could have some bread, as our ancestors did. But in combination with all other crap, it's way too much sugar.
If you eat cereal for breakfast, some rice and beans for lunch with a glass of orange juice you have already exceeded dietary sugar limits by a lot. And that's a far, far healthier diet than what's done in the average household.
Whereas if you had an avocado for breakfast, meat and vegetables for lunch you would be in a far better shape (literally and figuratively) even if the second diet had more calories. Calories are not all the same, and calories contained in food are not the same as calories absorbed (or stored). We accept that, when we fuel our car, a bunch of energy in the fuel will be wasted. Somehow, when we count calories, we assume we'll absorb them all.
The end result is that we are prematurely aging (due to all the oxidative stress), getting diabetes, non alcoholic fatty liver disease, high blood pressure, gout, cardiac problems. Possibly even Alzheimers (research ongoing, but there's growing evidence) and a few types of cancers. Also oral health in general. Basically, most of the mortality these days is directly or indirectly linked to sugar and insulin resistance in general. 88% of Americans have some form of metabolic dysfunction.
> no excess fat
Too much fat is usually the symptom of a disease (generally metabolic illness). Just fat, by itself, can be ok(also depending on where it is) – there are fat people who are otherwise healthy (a tiny minority, but they exist). And there are people that are thin but otherwise unhealthy (TOFI, Thin on the Outside, Fat Inside). What commonly happens is that we get sick first (insulin resistance) and then we get fat. For most people, being obese is the symptom, not the cause.
Diabetes does not strike out of the blue, although if you ask most people, they got "surprise" diagnoses. You check your glucose levels, and they are normal. You keep checking them for a few years, they are normal. Then "out of the blue" they are outside limits, and you get a diagnosis of pre-diabetes (or full blown diabetes). What was missed all these years was that your body was fiercely fighting against the glucose increase by raising the amount of insulin produced. But there's only so much the body can make (and also the cells will be resisting that), at some point, the combination of not being able to increase production plus resistance will be too much to overcome. Insulin measurements are not part of standard bloodwork yet, but at least they are now including A1C.
Completely drop added sugar. Reduce sugar in all forms, added, "natural", it doesn't matter. A sane amount of fruits is ok for their other benefits. Increase the amount of fat and fiber. Hydrate. And then drop processed foods in general. That's how we survive until 'anti-aging' is available.
Nutrition is difficult to get right because of the contradictory and plain harmful information that we have been receiving for so long.
For example: is fruit juice "healthy"? Not really, when you consider that you are far more likely to consume way more fruit that you otherwise would, and a lot of fiber content is removed. We are unlikely to eat 10 oranges in a row, but that's easy in juice form. That's without extra sugar - if sugar is added, then it's just a soda with added nutrients. And the problem with that is that fructose is only metabolized by the liver (turning into triglycerides), with a mechanism that's comparable to the one used to metabolize alcohol.
We have been told that fat is bad. Due to consumer demand, the industry start removing fat content. But then things taste horrible, so the solution was to add sugar.
So now we are worse off: not only we are consuming a lot of sugar (75% of all products in the supermarket have sugar, including 'salty' ones), but we haven't even attacked the problem that prompted fat removal (increase in heart conditions) in the first place. Fructose in particular turns into triglycerides, and gets stored as fat(with uric acid as byproduct, with way more free radical formation than glucose, and it even uses up ATP). It didn't address the heart issue, and actually made it worse. People have become far more obese than when they ate fats, as fats (plus fiber) make you feel full for longer. It also screws up hunger hormones and sugar is addictive by itself.
Or let's take bread. White bread is starting to get considered harmful, but then the alternative that's pushed is whole bread. It matters very little. If that's all we ate, we could have some bread, as our ancestors did. But in combination with all other crap, it's way too much sugar.
If you eat cereal for breakfast, some rice and beans for lunch with a glass of orange juice you have already exceeded dietary sugar limits by a lot. And that's a far, far healthier diet than what's done in the average household.
Whereas if you had an avocado for breakfast, meat and vegetables for lunch you would be in a far better shape (literally and figuratively) even if the second diet had more calories. Calories are not all the same, and calories contained in food are not the same as calories absorbed (or stored). We accept that, when we fuel our car, a bunch of energy in the fuel will be wasted. Somehow, when we count calories, we assume we'll absorb them all.
The end result is that we are prematurely aging (due to all the oxidative stress), getting diabetes, non alcoholic fatty liver disease, high blood pressure, gout, cardiac problems. Possibly even Alzheimers (research ongoing, but there's growing evidence) and a few types of cancers. Also oral health in general. Basically, most of the mortality these days is directly or indirectly linked to sugar and insulin resistance in general. 88% of Americans have some form of metabolic dysfunction.
> no excess fat
Too much fat is usually the symptom of a disease (generally metabolic illness). Just fat, by itself, can be ok(also depending on where it is) – there are fat people who are otherwise healthy (a tiny minority, but they exist). And there are people that are thin but otherwise unhealthy (TOFI, Thin on the Outside, Fat Inside). What commonly happens is that we get sick first (insulin resistance) and then we get fat. For most people, being obese is the symptom, not the cause.
Diabetes does not strike out of the blue, although if you ask most people, they got "surprise" diagnoses. You check your glucose levels, and they are normal. You keep checking them for a few years, they are normal. Then "out of the blue" they are outside limits, and you get a diagnosis of pre-diabetes (or full blown diabetes). What was missed all these years was that your body was fiercely fighting against the glucose increase by raising the amount of insulin produced. But there's only so much the body can make (and also the cells will be resisting that), at some point, the combination of not being able to increase production plus resistance will be too much to overcome. Insulin measurements are not part of standard bloodwork yet, but at least they are now including A1C.
Completely drop added sugar. Reduce sugar in all forms, added, "natural", it doesn't matter. A sane amount of fruits is ok for their other benefits. Increase the amount of fat and fiber. Hydrate. And then drop processed foods in general. That's how we survive until 'anti-aging' is available.
> Completely drop added sugar. Reduce sugar in all forms, added, "natural", it doesn't matter.
From my experience, it's the sodium that's in things more than on them. When you look at the sodium content of a lot of processed food, the amount you might sprinkle on at serving time is pretty insignificant.
>Is there anything similar in the science of anti-aging? Where (A) The body of research is large, well established, and mostly uncontroversial; (B) The benefits and safety profile are good; (C) The majority of people who are serious about this stuff use it/take it/do it.
The sodium/potassium ratio, and particularly keeping it smaller. The top answer right now is "nutrition", but that's a hairball, and the Na/K is a bright spot that gets left out of the discussion precisely because it is much less controversial than the endless debate over macronutrients and staples. The sodium/potassium ratio has effects on:
hypertension: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....
stroke/CVD: https://bmjopen.bmj.com/content/6/7/e011632.short
bone density: https://academic.oup.com/jcem/article/87/5/2008/2846608
chronic kidney disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047877/
and even such seemingly unrelated conditions as depression: https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy...
and age-related cognitive decline: https://www.sciencedirect.com/science/article/pii/S258979182...
The sodium/potassium ratio, and particularly keeping it smaller. The top answer right now is "nutrition", but that's a hairball, and the Na/K is a bright spot that gets left out of the discussion precisely because it is much less controversial than the endless debate over macronutrients and staples. The sodium/potassium ratio has effects on:
hypertension: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....
stroke/CVD: https://bmjopen.bmj.com/content/6/7/e011632.short
bone density: https://academic.oup.com/jcem/article/87/5/2008/2846608
chronic kidney disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047877/
and even such seemingly unrelated conditions as depression: https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy...
and age-related cognitive decline: https://www.sciencedirect.com/science/article/pii/S258979182...
But where can we get potassium from?? I feel like when I've looked, it's harder to come by than other vitamins/minerals
In general, potassium is found in fruits and vegetables. It has to be spread throughout the day, because high quantities of potassium at once have a laxative effect. The highest concentrations are found in some vegetable concentrates — the densest source in your cabinet is probably tomato sauce. It is present in milk and yogurt but not in cheese.
Potatoes and other starchy vegetables like squash and plantains have significantly more potassium than grains, but it's not necessary to completely give up grains. I usually put a 50/50 potassium/sodium ("Lite") salt on the oatmeal or grits I make for lunch (work requires speed), but I don't bother with it otherwise.
Potatoes and other starchy vegetables like squash and plantains have significantly more potassium than grains, but it's not necessary to completely give up grains. I usually put a 50/50 potassium/sodium ("Lite") salt on the oatmeal or grits I make for lunch (work requires speed), but I don't bother with it otherwise.
Creatine for brain health is unbelievably good too IIRC (don't quote me on it though, please! ;P)
One of the hard parts of aging stuff is how nonlinear it is. A lot of the good drug treatments seem to be short term/cyclical, along with significant lifestyle modifications.
In addition to what the other commenter said, I've heard of OMAD and having a strong community/having a purpose or something to do as another strong factor in longevity, in the 90-100+ year olds in Japanese community for example. I can't remember if OMAD was correlated to that community or a different study, however.
One of the hard parts of aging stuff is how nonlinear it is. A lot of the good drug treatments seem to be short term/cyclical, along with significant lifestyle modifications.
In addition to what the other commenter said, I've heard of OMAD and having a strong community/having a purpose or something to do as another strong factor in longevity, in the 90-100+ year olds in Japanese community for example. I can't remember if OMAD was correlated to that community or a different study, however.
Can you say some more about brain health, like how much creatine to take, what the expected benefits are, please?
Here is a good article, I think my favorite part is the paragraph containing reference #146: https://www.mdpi.com/2072-6643/14/5/921
Do you give any credence to the reports that creatine can cause hair loss? It seems like one study found a link, but nobody has tried to directly replicate it since. Anecdotally, Reddit is filled with stories of people claiming it caused hair loss, though I’m sure there are a ton of confounding variables.
Seems to be one of those topics... but anyway this study from 2009 found that creatine did in fact increased DHT.
https://pubmed.ncbi.nlm.nih.gov/19741313/
To be clear, no one is arguing that Creatine causes hairloss, simply that it exacerbates hairloss in people with so called androgenetic alopecia.
I recall a study that was set to try and replicate these results, but I worry that it was impacted by COVID. If anyone else can find it, I'd be very interested to see it.
https://pubmed.ncbi.nlm.nih.gov/19741313/
To be clear, no one is arguing that Creatine causes hairloss, simply that it exacerbates hairloss in people with so called androgenetic alopecia.
I recall a study that was set to try and replicate these results, but I worry that it was impacted by COVID. If anyone else can find it, I'd be very interested to see it.
I think people will always seek dubious explanations for why they're balding apart from "bad luck" and "you're old".
Well, people who use creatine also have a greater chance of having dihydrotestosterone, if I recall correctly....
Honestly hard to say, because that doesn't immediately "disprove" it either....
Honestly hard to say, because that doesn't immediately "disprove" it either....
Anecdotally, creatine makes me angry and a little unhinged. I've found evidence of other people complaining about this but it's not considered a known side effect. YMMV
Yes, creatine is everything you say, but it also seems to cause hair loss in males with male pattern baldness. If you look at youtube videos (for example) they often dismiss that, and then you see comment after comment of people who started losing hair. I'd use it in a heartbeat, but when I did my hair came out in the shower undeniably more. Boo. :(
The study I'm aware of documents a links between biomarkers associated with hair loss and creatine supplementation. Not between supplementation and hair loss. Without clinical data actually demonstrating this, its FUD.
Just because something isn't studied doesn't mean it should be dismissed as FUD. It's just unstudied.
I have a hunch that lifting weights would qualify. Not a pill, but huge research behind its effectiveness at a host of things, including improved/maintained balance (when older, falling and breaking a hip is often the start of a downward spiral..)
What about nootropics? What is the creatine of the mind enhancing drugs?
Modafinil
Weight lifting, ironically.
(see the rating + probability of positive effect charts here. [Warning, this is another insane rabbit hole of research to fall into!]): https://troof.blog/posts/nootropics/
(see the rating + probability of positive effect charts here. [Warning, this is another insane rabbit hole of research to fall into!]): https://troof.blog/posts/nootropics/
[deleted]
The reason why anti-aging is hard is that humans are already very long lived for a large high metabolism mammal. As a result it's likely that evolution has already picked most of the low hanging fruit in humans. We're already optimized for decent longevity.
This is why you see so many promising longevity studies in mice that don't replicate in humans. Mice are not particularly long lived compared to humans, so it's much easier to extend their life spans.
This is why you see so many promising longevity studies in mice that don't replicate in humans. Mice are not particularly long lived compared to humans, so it's much easier to extend their life spans.
I can’t tell if this Turnbuckle protocol is going to be one of the most revolutionary things I’ve read or going to be like when Napoleon Dynamite puts on Uncle Rico’s time machine from the internet and shocks himself.
Likely if it works, it'll be one piece of the puzzle.
It's not all that hard to try to be honest. Some people have reported absolutely massive changes, some small, some little to none. One or two said decrease but there seemed to be maybe some valid external factors for that.
That's about the distribution one could expect if mitochondrial damage was at play and there was an effective solution for it. Not everyone is going to respond well, likely the older the better if it actually is doing what it says on the tin.
It's not all that hard to try to be honest. Some people have reported absolutely massive changes, some small, some little to none. One or two said decrease but there seemed to be maybe some valid external factors for that.
That's about the distribution one could expect if mitochondrial damage was at play and there was an effective solution for it. Not everyone is going to respond well, likely the older the better if it actually is doing what it says on the tin.
That's about the distribution one could expect for placebo too.
Could be. Longecity I've found to be an odd mix of people who are rather combative about whether things work or not and who are way too in-depth (in a good way) about their personal experiences about what worked or not.
At the very least, it's intriguing and out of all of the thousands of pages of medical literature I've read over the past half decade or so it's been one of the more interesting sagas to follow.
At the very least, it's intriguing and out of all of the thousands of pages of medical literature I've read over the past half decade or so it's been one of the more interesting sagas to follow.
I have an intuition that if we are to find a solution it is more likely to first sprout from fringe experimentation, such as from Longecity, than the academy.
What do you make of all that in the last link?
At a cursory glance, it seems like the biohackers may simply be poisoning themselves on "fission" days and riding the rebound— eventually habituating to the fission supplements (a la arsenic eaters) so they feel less bad on the fission days (which they attribute to mitochondrial repair).
At a cursory glance, it seems like the biohackers may simply be poisoning themselves on "fission" days and riding the rebound— eventually habituating to the fission supplements (a la arsenic eaters) so they feel less bad on the fission days (which they attribute to mitochondrial repair).
Thanks for taking a gander! It is a very curious thread indeed (especially as you go deeper and deeper into its depths). Might I ask what makes you feel it is poisoning?
It is safe doses of well-known supplements (and works for other swaps in their classes -- like apigenin, sulfuraphane, etc).
Curious to hear though the thoughts on the poisoning line.
It is safe doses of well-known supplements (and works for other swaps in their classes -- like apigenin, sulfuraphane, etc).
Curious to hear though the thoughts on the poisoning line.
> Might I ask what makes you feel it is poisoning?
I definitely didn't mean to imply that I necessarily believe its poisoning. Apparently the neurotic and anti-interventionist in me reared its head when reading the thread.
I didn't recognize any of the supplement names, and so I didn't realize they all had reasonable safety profiles (individually?).
I think my point still stands though. From what I saw, the outcomes were deemed positive as a function of subjective reports of well-being, without controls. It seems plausible the protocol is having any range of effects (from negative to null to positive)— I just didn't see anything other than placebo-uncontrolled anecdata.
This is not to discount their efforts! I am truly interested in the subject.
I definitely didn't mean to imply that I necessarily believe its poisoning. Apparently the neurotic and anti-interventionist in me reared its head when reading the thread.
I didn't recognize any of the supplement names, and so I didn't realize they all had reasonable safety profiles (individually?).
I think my point still stands though. From what I saw, the outcomes were deemed positive as a function of subjective reports of well-being, without controls. It seems plausible the protocol is having any range of effects (from negative to null to positive)— I just didn't see anything other than placebo-uncontrolled anecdata.
This is not to discount their efforts! I am truly interested in the subject.
I think these are very good points! I understand what you're saying better now. :) <3
Having lifted weights regularly for years, it's profoundly weird for me to see someone reporting doing curls to failure for even just that period of time without improving their results. While I get the person in question just used that as some curious proxy measure, it makes the whole thing seem counterproductive...
There may be better anti-aging drugs that have yet to be tested or discovered, but Rapamycin currently has the best data backing it up. It is the only drug which has consistently increased both median and maximum lifespan across organisms, for both males and females, across many trials. It has also been shown to increase lifespan when given to organisms after they have reached their middle age, which is not common.
The Interventions Testing Program (ITP) by the NIH, which has been testing substances for their effects on lifespan for over 15 years, is regarded as the gold standard for testing possible lifespan increasing substances. Rapamycin has outperformed every other substance they have tested, by a wide margin. There is only one other substance they have tested that has shown a median and maximum lifespan increase, for both females and males, that being acarbose. The greatest lifespan increase observed in any of the trials was seen with the combination of rapamycin and acarbose.
All of the substances that NIH ITP have tested with their results listed, as well as the interventions they are testing now: https://www.nia.nih.gov/research/dab/interventions-testing-p...
List of the substances they have tested with charts showing the relative increase in lifespan: https://phenome.jax.org/projects/ITP1
The Interventions Testing Program (ITP) by the NIH, which has been testing substances for their effects on lifespan for over 15 years, is regarded as the gold standard for testing possible lifespan increasing substances. Rapamycin has outperformed every other substance they have tested, by a wide margin. There is only one other substance they have tested that has shown a median and maximum lifespan increase, for both females and males, that being acarbose. The greatest lifespan increase observed in any of the trials was seen with the combination of rapamycin and acarbose.
All of the substances that NIH ITP have tested with their results listed, as well as the interventions they are testing now: https://www.nia.nih.gov/research/dab/interventions-testing-p...
List of the substances they have tested with charts showing the relative increase in lifespan: https://phenome.jax.org/projects/ITP1
They're recommending Nicotinamide Riboside which has been implicated in increasing cancers.
My heuristics researching supplements, nootropics, longevity, are that the lab-created substances are more often than not, new and poorly studied, leading to eventual realization of more harm than they treat. Most recent, to me, was Alpha-GPC causing strokes.
My heuristics researching supplements, nootropics, longevity, are that the lab-created substances are more often than not, new and poorly studied, leading to eventual realization of more harm than they treat. Most recent, to me, was Alpha-GPC causing strokes.
That’s not very accurate. It wasn’t implicated in actually causing cancers. Tumour cells happen to have a high demand for NAD+, and NR provides them with that. So, if you already have tumours, NR will accelerate their growth. However also if you have had cancer recently and even if there are no more detectable signs, it is still possible for some tumour cells to be present; in that case NR is also risky. But if you are healthy, NR is not a carcinogen and any risk of stimulating the odd tumour cell is probably offset by the benefits NR provides to the immune system.
I think you're assuming the body doesn't form small tumors and destroy them naturally.
If something else is helping the tumors grow faster than the body can kill them naturally - then it's going to result both more severe tumors AND more tumors in general (as we discover them, since we usually don't know about tumors that form and get destroyed by the body naturally).
If something else is helping the tumors grow faster than the body can kill them naturally - then it's going to result both more severe tumors AND more tumors in general (as we discover them, since we usually don't know about tumors that form and get destroyed by the body naturally).
Covered in the last sentence.
This is an excellent direct summarization of NR<->Cancer. Thank you for sharing this, I greatly appreciate it. <3 :)
Not everyone needs NR necessarily (or any of the other forms), but it does seem to get more important as we get older and our ability to manufacture NMN goes down (IIRC that's the main target that's limited here?)
Not everyone needs NR necessarily (or any of the other forms), but it does seem to get more important as we get older and our ability to manufacture NMN goes down (IIRC that's the main target that's limited here?)
IIRC isn't NAC similar? It's not carcinogenic itself, but the benefits it provides also extend to the cancer cells?
NAC is a glutathione precursor. It is both anti- and pro- cancer. It is anti-cancer in a sense that glutathione reduces the risk of getting cancer in the first place. It is pro-cancer in a sense that it reduces the power of immune response due to reduction of the amount of produced ROS, which may theoretically lead to a faster cancer spread.
So yeah, they both are kind of similar in that dimension.
So yeah, they both are kind of similar in that dimension.
I can't speak either way on the cancer effects, but fun fact to all reading, NAC is a great glutamate mop because glutathione is made of 3 amino acids, IIRC, and glutamate is one of them. NAC is literally just glutathione without the glutamate, and it crosses the BBB and such more easily too, I believe?
In any case, it grabs onto free glutamate, and, whammo! less glutamate, instant glutathione. quite the nifty trick.
has some interesting data/studies backing it up, and also has some great psychiatric effects as well. IIRC it's used for schizophrenia among other things.
In any case, it grabs onto free glutamate, and, whammo! less glutamate, instant glutathione. quite the nifty trick.
has some interesting data/studies backing it up, and also has some great psychiatric effects as well. IIRC it's used for schizophrenia among other things.
Like all things, it's about balance. In this case, NR was recommended as a cheaper alternative to NMN, I believe, though one can take Nicotinamide and Ribose separately IIRC (ribose is expensive either way, lol. Tastes great though, a very, very fancy sugar indeed).
As far as cancer goes, basically half of the solutions here will cause cancer. That doesn't mean they're bad. Anything involving the body is extraordinarily nonlinear, so extrapolation is extremely hard in a variety of circumstances. You can find a study involving almost everything you consume and take linking it to a variety of things, it's just whether or not it's relevant to people in the doses and in the duration that they take them.
Especially on the cancer side of things, that's just a very delicate matter to be handled. Cleaning things up in theory should reduce the risk of cancer overall, even if ingredients on their own at some dose could cause issues.
A lot of these compounds have been around for or have been studied for 40-50 years or so. Some of the long-term effects are harder to pinpoint, but I'd be careful in seeking too much caution (in the same way I'd encourage someone not to go headlong throwing stuff into their bodies for no good reason). It's really easy to find nonlinear red lights for almost anything in medicine, in my (albeit limited) personal experience.
As far as cancer goes, basically half of the solutions here will cause cancer. That doesn't mean they're bad. Anything involving the body is extraordinarily nonlinear, so extrapolation is extremely hard in a variety of circumstances. You can find a study involving almost everything you consume and take linking it to a variety of things, it's just whether or not it's relevant to people in the doses and in the duration that they take them.
Especially on the cancer side of things, that's just a very delicate matter to be handled. Cleaning things up in theory should reduce the risk of cancer overall, even if ingredients on their own at some dose could cause issues.
A lot of these compounds have been around for or have been studied for 40-50 years or so. Some of the long-term effects are harder to pinpoint, but I'd be careful in seeking too much caution (in the same way I'd encourage someone not to go headlong throwing stuff into their bodies for no good reason). It's really easy to find nonlinear red lights for almost anything in medicine, in my (albeit limited) personal experience.
I think most people would agree that taking carcinogens will more likely reduce your lifespan than the possibility of significantly extending it.
For now, I'd rather bet on very clean air, very clean water, fasting, organic vegetables, green tea, omega 3 fish oil, well monitored sleep, and lots of exercise for longevity.
For now, I'd rather bet on very clean air, very clean water, fasting, organic vegetables, green tea, omega 3 fish oil, well monitored sleep, and lots of exercise for longevity.
That does feel like an overly simplistic argument. Once again, lots and lots of things feed cancer, it's not as simple as that. There's also a big 'might' clause, which means it's something that's going to take time to understand. For example, IIRC, the role that NR might play in cancers is that it's a very accessible food source for them. However, compared to other factors, this might fade into the woodwork, especially if for example it's used as part of a protocol that lowers the chance of cancer (or at the very least, all-cause mortality) longer term. Ideally, at least.
Maybe an analogy to communicate the concept is that it is like putting a car up on jacks and taking out parts to repair another part. It's possible that it is not where you are long-term, or ideal to do extremely frequently, but it's important to keep the thing maintained and running.
That said, I agree very much on your last sentence as one of the best "simple" routines to get bang for the buck. My thoughts would be weight lifting specifically, chamomile tea at night (apigenin is something else), as well as some broccoli sprouts for NRF2 in there. Other than that I think that's probably the index fund-like strategy to longevity, so we're definitely on the same page there. :D :thumbsup:
Maybe an analogy to communicate the concept is that it is like putting a car up on jacks and taking out parts to repair another part. It's possible that it is not where you are long-term, or ideal to do extremely frequently, but it's important to keep the thing maintained and running.
That said, I agree very much on your last sentence as one of the best "simple" routines to get bang for the buck. My thoughts would be weight lifting specifically, chamomile tea at night (apigenin is something else), as well as some broccoli sprouts for NRF2 in there. Other than that I think that's probably the index fund-like strategy to longevity, so we're definitely on the same page there. :D :thumbsup:
This sounds like the chemical reasoning of homeopathy to me.
Not necessarily.
I can give an analogous example.
Lengthening telomeres is a naive strategy some chase for longevity. You can think of telomeres as aglets for DNA -- they shorten as you get older. So inhibiting that shortening is good, right?
Well, that does extend life, in a way, but it also slows down DNA repair and makes that a harder thing to access, because now damaged DNA has longer end-caps on it too.
So of course a few years after the whole "Just take telomere lengtheners!" headline wave, another headline wave of "Telomere lengtheners actually can worsen aging!" is a decent followup to expect (something like this happened IRL IIRC).
You can make a similar analogy with stem cells and a limited stem cell pool (do you deplete the pool early, assuming it no longer regenerates at this point, for a boost of apparent vitality, or ration it over the course of a lifetime?)
Homeopathy on the other hand assumes a bizzare, quantum-like "memory" in molecules that has not been shown to be accurate by science, but excels as being a placebo effect.
These are quite different phenomena. It's another way of saying "the dose makes the poison", though in this case, it's "the dose has varying and highly state-dependent effects within a strongly chaotic dynamical system".
I can give an analogous example.
Lengthening telomeres is a naive strategy some chase for longevity. You can think of telomeres as aglets for DNA -- they shorten as you get older. So inhibiting that shortening is good, right?
Well, that does extend life, in a way, but it also slows down DNA repair and makes that a harder thing to access, because now damaged DNA has longer end-caps on it too.
So of course a few years after the whole "Just take telomere lengtheners!" headline wave, another headline wave of "Telomere lengtheners actually can worsen aging!" is a decent followup to expect (something like this happened IRL IIRC).
You can make a similar analogy with stem cells and a limited stem cell pool (do you deplete the pool early, assuming it no longer regenerates at this point, for a boost of apparent vitality, or ration it over the course of a lifetime?)
Homeopathy on the other hand assumes a bizzare, quantum-like "memory" in molecules that has not been shown to be accurate by science, but excels as being a placebo effect.
These are quite different phenomena. It's another way of saying "the dose makes the poison", though in this case, it's "the dose has varying and highly state-dependent effects within a strongly chaotic dynamical system".
Cancer thrives on any kind of NAD source, not specifically Nicotinamide Riboside. Even milk poses a risk of increased tumor growth (it contains NAD, a lot of it). But it only applies to those who have the ongoing oncology in the first place, so... blaming NR for causing cancers is probably a misfire.
Many people have small, slow growing tumors which aren't currently causing clinical symptoms and may not even be reliably detectible through the usual screening tests.
“I can do more for you if you just eat right and exercise” - Dr. McCoy from “The Omega Glory” ST:TOS
Is there anything in the works that can break down lipofuscein or advanced glycation endproducts? Those always seem under-discussed.
I try to keep up with the AGE breaker development, I thought there were at least one or two labs/companies trying to develop them.
I think IIRC that the crosslink breakers (referring to AGE above for those OOTL) mainly struggle from delivery being difficult? Because many of the AGEs we care about can end up in some bizzare, hard-to-reach places? I think?
I don't think this is directly related but there was one therapy for cellulite that just had an enzyme that dissolved collagen. I just learned that they (sadly, in the long run for the research field in that area) had to shutter that after only two years or so, apparently due to the bruising and discoloration of skin long term (https://investor.endo.com/news-releases/news-release-details...). I guess I can only feel so bad as they were marketing pretty heavily to people who were rich enough to pay for the cosmetic surgery out of pocket, and were as well in a category of middle-aged "luxury" buyers (from the official website -- I don't think the wayback machine will show the pictures [warning, very butt focused], but perhaps for the better, the saved version has the desktop and mobile transcript. Confetti for a medical drug advertisement website. Incredible: https://web.archive.org/web/20210124142605/https://www.qwo.c...)
Lipofuscein I'd love to learn about, I have not heard of that before.
I think IIRC that the crosslink breakers (referring to AGE above for those OOTL) mainly struggle from delivery being difficult? Because many of the AGEs we care about can end up in some bizzare, hard-to-reach places? I think?
I don't think this is directly related but there was one therapy for cellulite that just had an enzyme that dissolved collagen. I just learned that they (sadly, in the long run for the research field in that area) had to shutter that after only two years or so, apparently due to the bruising and discoloration of skin long term (https://investor.endo.com/news-releases/news-release-details...). I guess I can only feel so bad as they were marketing pretty heavily to people who were rich enough to pay for the cosmetic surgery out of pocket, and were as well in a category of middle-aged "luxury" buyers (from the official website -- I don't think the wayback machine will show the pictures [warning, very butt focused], but perhaps for the better, the saved version has the desktop and mobile transcript. Confetti for a medical drug advertisement website. Incredible: https://web.archive.org/web/20210124142605/https://www.qwo.c...)
Lipofuscein I'd love to learn about, I have not heard of that before.
Interesting stuff, glad to see that the research is continuing in this area. I'm thinking about experimenting with topical alagebrium just to see if it does anything. I recall a study in mice that found a very significant effect on skin wrinkles in aged animals.
And it's lipofuscin, I mistyped it. Basically oxidized junk molecules that never seem to get broken down and just accumulate within the cell with age. Interestingly, piracetam seems to have a positive effect on this in rodent brains.
And it's lipofuscin, I mistyped it. Basically oxidized junk molecules that never seem to get broken down and just accumulate within the cell with age. Interestingly, piracetam seems to have a positive effect on this in rodent brains.
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There's a great Radiolab episode on this topic and the person who first isolated it.
https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub
I second this podcast, great vivid storytelling.
Many of us know and follow rapamycin's story. There are some Drs in USA who're willing to prescribe it for longevity. I do hope some billionare will be willing to spend a few million on it to test it in clinical trials. Surely one of the most promising molecules out there, and very little sides when dosed intermittently.
From the article, this molecule sounds like a big hammer that you can pound cell reproduction with, affecting a wide range of systems in unpredictable ways. Whereas what we need are precision watchmaker tools and a diagram of the watch.
On thing I think is well established about aging is that it's not a single factor disease that you can "cure" by removing a well defined cause. Rather, it's a pervasive accumulation of entropy in various systems from various causes that evolution had no ability to correct, so that slowing aging down and reversing it involves a massive amount of tinkering with the watch.
On thing I think is well established about aging is that it's not a single factor disease that you can "cure" by removing a well defined cause. Rather, it's a pervasive accumulation of entropy in various systems from various causes that evolution had no ability to correct, so that slowing aging down and reversing it involves a massive amount of tinkering with the watch.
The anti-aging effects of rapamycin support the opposite of "pervasive accumulation of entropy" theory - which is that aging is a distorted development program, rather than random accumulation of entropy.
The definition of "random" implies by default that lack of information or knowledge on the object in question is primarily due to cognitive (and hence measurement) limitations of its users, rather than something being 100% objectively ingrained in reality.
The definition of "random" implies by default that lack of information or knowledge on the object in question is primarily due to cognitive (and hence measurement) limitations of its users, rather than something being 100% objectively ingrained in reality.
Only chink in that theory is rapamycin doesn't seem to have anti-aging effects per-se, rather a wide array of systemic effects, some beneficial to longevity in special circumstances. In the general case, you definitely won't be extending lifespan of the elderly by modulating down their immune system or promoting amyloid formations.
There is definitely "real" randomness, DNA replication errors are truly random because they are caused by quantum molecular effects. You can characterize them statistically and reduce their incidence, for example by controlling the diet or shielding the body from UV, but you can't measure those causes, only observe their effects. At best you could correct them, starting from a known-good-copy, as indeed cell biology already does.
There is definitely "real" randomness, DNA replication errors are truly random because they are caused by quantum molecular effects. You can characterize them statistically and reduce their incidence, for example by controlling the diet or shielding the body from UV, but you can't measure those causes, only observe their effects. At best you could correct them, starting from a known-good-copy, as indeed cell biology already does.
It has so many immunity-related side effects IIRC.
Lowering the drawbridge and opening the gate lets a lot of things happen/go in, both good and bad.
I've heard that it's oftentimes a trade between two extremes, cancer or...well to be honest I've completely forgotten the second one. Huh.
Lowering the drawbridge and opening the gate lets a lot of things happen/go in, both good and bad.
I've heard that it's oftentimes a trade between two extremes, cancer or...well to be honest I've completely forgotten the second one. Huh.
There are quite a few studies ongoing in '22 and '23.
https://www.rapamycin.news/t/rapamycin-clinical-trial-update...
https://www.rapamycin.news/t/rapamycin-clinical-trial-update...
Rapamycin is also being studied as a booster drug to ketamine for treatment-resistant depression
https://www.bbrfoundation.org/content/surprising-clinical-tr...
https://www.bbrfoundation.org/content/surprising-clinical-tr...
Yes, my ketamine doctor actually suggested this last year and prescribed me rapamycin as a booster with ketamine infusion sessions, citing this study referenced. He's done this for some patients who don't get infusions frequently, to try and stretch the positive effects longer.
It had a bit strange effects the first time I took the rapa, you dose it about 2 hours before ketamine infusion session. It actually attenuated the psychedelic effects of ketamine quite dramatically, which is interesting because the study predicted the rapamycin to strongly counteract certain effects of ketamine action, but the physical ketamine effects were still present for me. I did have the same positive mood boost starting later that day that I was used to with the infusions, I don't think the rapamycin hurt that effect and I was left with a good effect for some time afterwards.
What I was left wondering is, is the rapamycin actually amplifying the ketamine mood boost, or does it simply have a separate antidepressant effect that you can layer on by co-administering it? I took the rapamycin a couple times outside of session, and it did seem to give me an antidepressant effect for a few days as far as I can tell, of course not in a controlled study environment. But internally, I concluded that ketamine and rapamycin both have antidepressant effects that can both be used to positive effect, together or separately.
It had a bit strange effects the first time I took the rapa, you dose it about 2 hours before ketamine infusion session. It actually attenuated the psychedelic effects of ketamine quite dramatically, which is interesting because the study predicted the rapamycin to strongly counteract certain effects of ketamine action, but the physical ketamine effects were still present for me. I did have the same positive mood boost starting later that day that I was used to with the infusions, I don't think the rapamycin hurt that effect and I was left with a good effect for some time afterwards.
What I was left wondering is, is the rapamycin actually amplifying the ketamine mood boost, or does it simply have a separate antidepressant effect that you can layer on by co-administering it? I took the rapamycin a couple times outside of session, and it did seem to give me an antidepressant effect for a few days as far as I can tell, of course not in a controlled study environment. But internally, I concluded that ketamine and rapamycin both have antidepressant effects that can both be used to positive effect, together or separately.
Tangentially related: Fable of the Dragon-Tyrant[0].
0. https://www.youtube.com/watch?v=cZYNADOHhVY
0. https://www.youtube.com/watch?v=cZYNADOHhVY
I didn't realize this short was first a textual story [1] until years after my first encounter.
[1] https://nickbostrom.com/fable/dragon
[1] https://nickbostrom.com/fable/dragon
Me neither. Thank you for bringing it to my attention.
Today, I also learned about xianxia[0] from an unexpected place[1].
0. https://en.wikipedia.org/wiki/Xianxia
1. https://hsr.hoyoverse.com/
Today, I also learned about xianxia[0] from an unexpected place[1].
0. https://en.wikipedia.org/wiki/Xianxia
1. https://hsr.hoyoverse.com/
The part where a compound first investigated as an antifungal improves longevity of fungi wasn't really explored, but eh?
Is it controlling fungi that infect other fungi or something?
Is it controlling fungi that infect other fungi or something?
Sounds like this would have been a great candidate for covid patients with immune system issues...like cytokine storms etc.
Sorry for the meta-commentary but…
HN’s anti-aging obsession is wild.
I get zero anti-aging content from any other news source, user submitted or otherwise, and yet without fail it seems like there’s at least one anti-aging article a week on HN. Any other topic I find on HN I run into elsewhere: space, JavaScript, crypto, lisp, etc etc. Only on HN do I regularly see anti-aging “news” promoted.
The discussions are all about the same: it’s a scam! It’s worth a shot! More research is needed! Anti-aging is unnatural! Anti-aging is a biological imperative!
idk it must have fans to get so consistently upvoted, but I do not get the appeal.
HN’s anti-aging obsession is wild.
I get zero anti-aging content from any other news source, user submitted or otherwise, and yet without fail it seems like there’s at least one anti-aging article a week on HN. Any other topic I find on HN I run into elsewhere: space, JavaScript, crypto, lisp, etc etc. Only on HN do I regularly see anti-aging “news” promoted.
The discussions are all about the same: it’s a scam! It’s worth a shot! More research is needed! Anti-aging is unnatural! Anti-aging is a biological imperative!
idk it must have fans to get so consistently upvoted, but I do not get the appeal.
HN has always had some science content not just tech. Articles about fusion and batteries get promoted here often. If all your other sources are pure software focused it would make sense you dont see aging there.
As for the actual topic. Lots of people talk about fear of death, and i am sure that plays a part. For me though, i think its interesting because people have been trying to increase longevity since forever and haven't succeded yet. There is something fascinating about a problem everyone has tried to solve but still isn't solved.
As for the actual topic. Lots of people talk about fear of death, and i am sure that plays a part. For me though, i think its interesting because people have been trying to increase longevity since forever and haven't succeded yet. There is something fascinating about a problem everyone has tried to solve but still isn't solved.
The median lifespan is ~77 years but some people live to ~115. That's quite a difference. Some of that may be genetics but not all of it. The median person who dies at 95 is doing something different than the median person who dies at 60. The least we can do is find out what.
And maybe if we do, someone could live to be 130, or still be in good health at 95.
And maybe if we do, someone could live to be 130, or still be in good health at 95.
There's a mindset amongst hackers that you can hack yourself, hence the popularity of life hacks, discussions of all sorts of drugs. I think it's up to each individual to decide whether they want to go that route and experiment with themselves or not...!
It's a valid topic of discussion around here because people are educated enough to consider medical anti-aging as a plausible thing, whereas in other demographics you would be ridiculed as an idiot with a God delusion.
But anti-aging in general is a topic permeating our entire society, from non-stop commercials to "rejuvenating" cosmetics and dead-sea-mineral-spas, to the boom of plastic surgery, to the fad diets promising a long healthy life, if we look around everybody talks about it one way or another because nobody wants to get old.
But anti-aging in general is a topic permeating our entire society, from non-stop commercials to "rejuvenating" cosmetics and dead-sea-mineral-spas, to the boom of plastic surgery, to the fad diets promising a long healthy life, if we look around everybody talks about it one way or another because nobody wants to get old.
Such an educated audience. And brilliant too. Other demographics can't hold a candle to how smart and also cool HNers are.
You forgot attractive; nothing but raw sexual energy from this bunch.
I do not get why you do not get the appeal. Do you want to die?
It's not about not wanting to die. It's about death being inevitable. Everything dies, or breaks down, or decays. That's just how the universe works.
The best you'll get is extended life, and that's never going to be enough - there's always going to be someone trying to push that limit out a little further. IMO, what matters more, and what some folks here have brought up, is more healthy years. I think wanting to be fitter and healthier in old age is pretty uncontroversial, but the problem is that it gets rolled up with immortality, because getting to say "We conquered death" would be way sexier than saying "We extended good living by a decade or two (and that's being optimistic)".
Immortality has been, and always will be, a fantasy. Better that those resources go to something more productive, like healthcare.
The best you'll get is extended life, and that's never going to be enough - there's always going to be someone trying to push that limit out a little further. IMO, what matters more, and what some folks here have brought up, is more healthy years. I think wanting to be fitter and healthier in old age is pretty uncontroversial, but the problem is that it gets rolled up with immortality, because getting to say "We conquered death" would be way sexier than saying "We extended good living by a decade or two (and that's being optimistic)".
Immortality has been, and always will be, a fantasy. Better that those resources go to something more productive, like healthcare.
> Everything dies, or breaks down, or decays. That's just how the universe works.
Sure, that's entropy, but that's only necessarily true at the level of the whole system, energy inputs can and do reduce local entropy.
> The best you'll get is extended life
Sounds good, let's start there. 'True' immortality may or may not be a pipe dream, but it doesn't matter if it is. Almost nobody is talking about living absolutely forever, but looking at ways in which greater longevity can be achieved. I'd bite your hand off for another couple of decades on top of whatever my current 'allocation' might be, I don't give a crap if we've "conquered death" or not, but if we can find ways to give the average person more time, that seems like a win.
> Better that those resources go to something more productive, like healthcare.
How is this not healthcare?
There seems to be this backlash against any talk of life extension, that other things matter more, that it's somehow frivolous, or just morally wrong to seek to live longer. It feels to me entirely arbitrary as we already use all sorts of interventions to help people live longer, and to be healthier for more of that time. This is good and wise and virtuous. But some folks seem to have this weird switch in their heads when extending life gets mentioned, that suddenly they're uncomfortable and the whole thing is not to be discussed by preference.
And I wonder if it's because they don't want to admit to themselves or others that they are terrified, but have rationalised away their fear as "meant to be, can't be changed". Such talk of extension makes them uncomfortable.
Sure, that's entropy, but that's only necessarily true at the level of the whole system, energy inputs can and do reduce local entropy.
> The best you'll get is extended life
Sounds good, let's start there. 'True' immortality may or may not be a pipe dream, but it doesn't matter if it is. Almost nobody is talking about living absolutely forever, but looking at ways in which greater longevity can be achieved. I'd bite your hand off for another couple of decades on top of whatever my current 'allocation' might be, I don't give a crap if we've "conquered death" or not, but if we can find ways to give the average person more time, that seems like a win.
> Better that those resources go to something more productive, like healthcare.
How is this not healthcare?
There seems to be this backlash against any talk of life extension, that other things matter more, that it's somehow frivolous, or just morally wrong to seek to live longer. It feels to me entirely arbitrary as we already use all sorts of interventions to help people live longer, and to be healthier for more of that time. This is good and wise and virtuous. But some folks seem to have this weird switch in their heads when extending life gets mentioned, that suddenly they're uncomfortable and the whole thing is not to be discussed by preference.
And I wonder if it's because they don't want to admit to themselves or others that they are terrified, but have rationalised away their fear as "meant to be, can't be changed". Such talk of extension makes them uncomfortable.
Your post is a good example on how even highly educated people need more education, how communication is an important thing in science and how framing changes perception of everything.
Anti-aging science is basically the most audacious preventative program out there. It is not really about "immortality" (even if this level of success were to be reached, one can always kill themselves, no biology will give you immunity to fast flying bullets), but an attempt to prevent or at least delay onset of a host of chronic diseases that are synonymous with aging.
"but the problem is that it gets rolled up with immortality"
Then don't contribute to that problem by insinuating that anti-aging is something different from healthcare. It is not, it is literally about extending healthspan, at least at this point. Rejuvenation means making people live longer by improving their metabolism etc.; how it is not healthcare in the best sense of the word (protecting health instead of treating already extant diseases)?
"Everything dies, or breaks down, or decays."
And yet you can keep your room tidy for long decades even if the entropy of the universe as such increases.
We have a lot of self-repair mechanisms, that is why we live longer than our relatives like dogs and mice. "The universe" does not dictate to us whether to get cancer or not; some species (like whales) seem to be very resistant to cancer and it is absolutely thinkable that we could acquire this ability too, if we happen to learn enough about metabolism. Etc. etc.
Human death at 80 isn't a result of laws of physics, any more than murine death at 2,5. It is a case of biological dysregulation that can possibly be fixed or at least improved, much like we improved other things about ourselves. Few of the HN crowd would proclaim wearing glasses to fix your vision to be unnatural. What we are looking for in anti-aging are "glasses for the body".
Anti-aging science is basically the most audacious preventative program out there. It is not really about "immortality" (even if this level of success were to be reached, one can always kill themselves, no biology will give you immunity to fast flying bullets), but an attempt to prevent or at least delay onset of a host of chronic diseases that are synonymous with aging.
"but the problem is that it gets rolled up with immortality"
Then don't contribute to that problem by insinuating that anti-aging is something different from healthcare. It is not, it is literally about extending healthspan, at least at this point. Rejuvenation means making people live longer by improving their metabolism etc.; how it is not healthcare in the best sense of the word (protecting health instead of treating already extant diseases)?
"Everything dies, or breaks down, or decays."
And yet you can keep your room tidy for long decades even if the entropy of the universe as such increases.
We have a lot of self-repair mechanisms, that is why we live longer than our relatives like dogs and mice. "The universe" does not dictate to us whether to get cancer or not; some species (like whales) seem to be very resistant to cancer and it is absolutely thinkable that we could acquire this ability too, if we happen to learn enough about metabolism. Etc. etc.
Human death at 80 isn't a result of laws of physics, any more than murine death at 2,5. It is a case of biological dysregulation that can possibly be fixed or at least improved, much like we improved other things about ourselves. Few of the HN crowd would proclaim wearing glasses to fix your vision to be unnatural. What we are looking for in anti-aging are "glasses for the body".
Yes, immortality sounds horrible.
> Do you want to live forever, Harry?"
> "Yes, and so do you," said Harry. "I want to live one more day. Tomorrow I will still want to live one more day. Therefore I want to live forever, proof by induction on the positive integers. If you don't want to die, it means you want to live forever. If you don't want to live forever, it means you want to die. You've got to do one or the other... I'm not getting through here, am I."
It would be interesting to see how society will change when we can make ourselves permanently healthy. Maybe people who want to die will start taking extreme risks like sky-diving or Russian roulette but the above quote stands imo. If you don't want to live any more sounds to me like you have a psychological problem. I don't mean that 80 year olds, that have a dozen physical problems and struggle to do anything and therefore want to die because life is unbearable, have a psychological problem but if you're young, healthy and still find no pleasure in living then maybe you should see a therapist. Maybe the psychological part of living forever needs to be solved too
> "Yes, and so do you," said Harry. "I want to live one more day. Tomorrow I will still want to live one more day. Therefore I want to live forever, proof by induction on the positive integers. If you don't want to die, it means you want to live forever. If you don't want to live forever, it means you want to die. You've got to do one or the other... I'm not getting through here, am I."
It would be interesting to see how society will change when we can make ourselves permanently healthy. Maybe people who want to die will start taking extreme risks like sky-diving or Russian roulette but the above quote stands imo. If you don't want to live any more sounds to me like you have a psychological problem. I don't mean that 80 year olds, that have a dozen physical problems and struggle to do anything and therefore want to die because life is unbearable, have a psychological problem but if you're young, healthy and still find no pleasure in living then maybe you should see a therapist. Maybe the psychological part of living forever needs to be solved too
"The water isn't boiling yet. In one minute the water will still not have boiled. Therefore it will take forever to bring this pot to boiling point, proof by induction on the positive integers."
I broadly agree with lifespan and healthspan extension on the grounds that one should get to choose the time and manner of their passing, but that quote is just ridiculous and Yudkowsky should have known better.
I broadly agree with lifespan and healthspan extension on the grounds that one should get to choose the time and manner of their passing, but that quote is just ridiculous and Yudkowsky should have known better.
That quote is from the perspective of an 11-year old. I'd say it fits the context and he wrote it well because even though it's not an accurate and perfect view it is funny
I personally think it would be so cool to see the world evolve over thousands of years.
Maybe we'd be nicer to each other if we lived that long, because we know our empire might be on top now, but likely not through our lifetime.
But wealth inequality would probably be even worse, because by the time one generation dies, they've already bought up every piece of land in the world.
Maybe we'd be nicer to each other if we lived that long, because we know our empire might be on top now, but likely not through our lifetime.
But wealth inequality would probably be even worse, because by the time one generation dies, they've already bought up every piece of land in the world.
that proof assumes the desire to live will remain constant over time but it will not. parts of the human body will decay and over time the will to live will drop.
death is inevitable. by artificially extending your lifespan, you're not becoming immortal. you're taking an event that typically comes as a natural part of life and is out of your control and forcing yourself to choose when it happens. you will have to choose at what point your agony is so unbearable that you no longer want to live.
people who are unlucky already have to live that hell in modern times. i don't think people chasing this fever dream have experienced the joy of seeing it play out.
death is inevitable. by artificially extending your lifespan, you're not becoming immortal. you're taking an event that typically comes as a natural part of life and is out of your control and forcing yourself to choose when it happens. you will have to choose at what point your agony is so unbearable that you no longer want to live.
people who are unlucky already have to live that hell in modern times. i don't think people chasing this fever dream have experienced the joy of seeing it play out.
If you can't picture yourself giving up an anti-aging treatment without "unbearable agony" forcing your hand, that's your psychological hangup, not everyone else's.
A normal person can just decide they're 200 and not really enjoying much anymore and have that be the end of it.
A normal person can just decide they're 200 and not really enjoying much anymore and have that be the end of it.
Even then, maybe first see a therapist, try some psychedelics or whatever. If you've tried everything and somehow still see no point in living then yeah.. go ahead.
I've been depressed a couple of times in my life and saw no point in going further or living but I've talked myself out of it by simply saying, hey, if I do this relatively small thing and then do this thing that gives me pleasure then that's better than literal death. I find it hard to believe a person has experienced everything there is to experience in 200 or even 1000 years. Our set of experiences is what it is because of the short time that we have but it doesn't mean it can't evolve to accommodate a lifespan of 10x or 100x.
I've been depressed a couple of times in my life and saw no point in going further or living but I've talked myself out of it by simply saying, hey, if I do this relatively small thing and then do this thing that gives me pleasure then that's better than literal death. I find it hard to believe a person has experienced everything there is to experience in 200 or even 1000 years. Our set of experiences is what it is because of the short time that we have but it doesn't mean it can't evolve to accommodate a lifespan of 10x or 100x.
i'm arguing against the idea of achieving "immortality", not against anti-aging treatments. slowing the progression of aging but maintaining the same trajectory of life and death is a desirable thing. trying to avoid death is not.
> parts of the human body will decay and over time the will to live will drop.
parts of the human body also evolve and strengthen over time, unfortunately evolution also made them decay after some point, that's what we're trying to fix.
> you're taking an event that typically comes as a natural part of life and is out of your control..
this whole paragraph could apply to any physical problem. You were born with XYZ health problem? just accept your fate, it's natural. You got bit by a dog? Natural, just accept your fate. You got an infection? why even bother taking antibiotics, you're just forcing yourself to live longer
parts of the human body also evolve and strengthen over time, unfortunately evolution also made them decay after some point, that's what we're trying to fix.
> you're taking an event that typically comes as a natural part of life and is out of your control..
this whole paragraph could apply to any physical problem. You were born with XYZ health problem? just accept your fate, it's natural. You got bit by a dog? Natural, just accept your fate. You got an infection? why even bother taking antibiotics, you're just forcing yourself to live longer
Your lifespan has already been artificially extended. It’s nearly twice the maximum of 10,000 years ago when most people were nomadic, and about 20–25% longer than that of the ancient Greeks, who retired from their militia at 65 only if they made it that long.
And most of that life is spent in healthy youth and middle age, not in continual decline. Today we expect to become elderly in our 70s or 80s, and then die. The Greeks became elderly in their 60s or even earlier. Is it so hard to believe that in another 100 years people could be living to their 90s or 100s before age catches up with them?
And most of that life is spent in healthy youth and middle age, not in continual decline. Today we expect to become elderly in our 70s or 80s, and then die. The Greeks became elderly in their 60s or even earlier. Is it so hard to believe that in another 100 years people could be living to their 90s or 100s before age catches up with them?
i agree with everything you said. what i don't agree with is that you can prove by induction that you want to live for eternity.
The choice of death is a very good point. One would argue that the difference between a natural death and a death sentence is the knowledge and control of your life’s termination.
If people decide to end themselves that is suicide, and if someone else decides it then that is murder. All these are morally and ethically much more complicated than just dying agentlessly.
If people decide to end themselves that is suicide, and if someone else decides it then that is murder. All these are morally and ethically much more complicated than just dying agentlessly.
To be honest, i've always wondered how many people would actually believe this if given the choice (assuming healthy immortality). It always struck me a bit as the sort of thing people say to be able to live with the fact they are going to die and there is nothing they can do about it. Always easier to accept something out of one's control by pretending it is what you wanted all along.
Immortality sounds horrible if and only if I'm the only one immortal.
Most people don't want to die. I want to learn more, and indulge curiosity for another day. I want to laugh and love and see my family forever longer - I don't think I'd ever wish to leave my loved ones, and I will unsurprisingly mourn their loss. I assume I'm not particularly special in any of this...
I think the sudden onset of immortality (especially concentrated on the wealthy) will be catastrophic for society. Imagine Bezos or a Kardashian or someone politically motivated like Murdoch/Soros but immortal? Imagine them being able to spend (and grow) generations of wealth... for generation?
For the rest of us, the cost of an opportunity to be immortal will be massive because of course it can be. People today save for retirement, but one day they may save for immortality - or perhaps take out insane loans to fund it. Imagine real estate prices when banks can offer 100y mortgages to a class of rich immortal workers? Imagine trying to advance in your career when someone can get a senior job and work for hundreds of years, especially if they need to fund their 100y mortgage or their immortality procedure - Millennials already complain that boomers won't retire and open up the higher-rung jobs.
Immortality would upend society, and likely exacerbate social tensions, but it could also be a great reset in social expectations. Maybe it'd encourage everyone to take a long-term view of their actions. eg. Climate change would impact everyone, so no one would be "too old to care".
Most people don't want to die. I want to learn more, and indulge curiosity for another day. I want to laugh and love and see my family forever longer - I don't think I'd ever wish to leave my loved ones, and I will unsurprisingly mourn their loss. I assume I'm not particularly special in any of this...
I think the sudden onset of immortality (especially concentrated on the wealthy) will be catastrophic for society. Imagine Bezos or a Kardashian or someone politically motivated like Murdoch/Soros but immortal? Imagine them being able to spend (and grow) generations of wealth... for generation?
For the rest of us, the cost of an opportunity to be immortal will be massive because of course it can be. People today save for retirement, but one day they may save for immortality - or perhaps take out insane loans to fund it. Imagine real estate prices when banks can offer 100y mortgages to a class of rich immortal workers? Imagine trying to advance in your career when someone can get a senior job and work for hundreds of years, especially if they need to fund their 100y mortgage or their immortality procedure - Millennials already complain that boomers won't retire and open up the higher-rung jobs.
Immortality would upend society, and likely exacerbate social tensions, but it could also be a great reset in social expectations. Maybe it'd encourage everyone to take a long-term view of their actions. eg. Climate change would impact everyone, so no one would be "too old to care".
Do you want to die earlier rather than later, and/or in worse health condition than possible?
That's what anti-aging is.
That's what anti-aging is.
Not OP, but my opinion is that I want to die when I'm supposed to, and I want everyone else to also. Time is the great equalizer, and the well to do's should not be able to purchase more.
The last time I wrote this opinion, I was met with everything from 'just kill yourself' to 'quit trying to control my life.'
Funny bunch here.
The last time I wrote this opinion, I was met with everything from 'just kill yourself' to 'quit trying to control my life.'
Funny bunch here.
The dying part bothers me less than the aging. I'd be fine dying at the "normal" age, but I'd rather do so with a healthier body than my grandparents.
And telling other people when they should die is sorta messed up. Ignore these anti-aging medications, should people be cut off other medicines at a certain point? What's the difference?
And telling other people when they should die is sorta messed up. Ignore these anti-aging medications, should people be cut off other medicines at a certain point? What's the difference?
I've had all these arguments before, that I don't care to have again.
> And telling other people when they should die is sorta messed up
I'm not telling other people when to die! I'm thinking more of a societal contract. Which in fairness, seem less and less these days.
Like, if I go to the back of a queue, and see you going to the front, and request you go to the back... I'm not trying to control your life. I'm just asking you to acknowledge and respect that we live in a society.
> And telling other people when they should die is sorta messed up
I'm not telling other people when to die! I'm thinking more of a societal contract. Which in fairness, seem less and less these days.
Like, if I go to the back of a queue, and see you going to the front, and request you go to the back... I'm not trying to control your life. I'm just asking you to acknowledge and respect that we live in a society.
>I've had all these arguments before, that I don't care to have again.
The arguenent of "I don't want to need help going to the bathroom/eating?" Or "I don't want to have effectively a two minute memory?" They're pretty solid arguments to me.
>I'm not telling other people when to die!
No, you want society to agree with you when people should die. This societal contract already does not exist. Maybe it'd be nice if it did, but you'd still need to answer the question of "should I stop this person from taking medicine because it's time for them to die?"
The arguenent of "I don't want to need help going to the bathroom/eating?" Or "I don't want to have effectively a two minute memory?" They're pretty solid arguments to me.
>I'm not telling other people when to die!
No, you want society to agree with you when people should die. This societal contract already does not exist. Maybe it'd be nice if it did, but you'd still need to answer the question of "should I stop this person from taking medicine because it's time for them to die?"
>Time is the great equalizer, and the well to do's should not be able to purchase more.
The entire medical (and dental) profession is all about keeping you from dying when you're "supposed to". You're supposed to die in your teenage years of a tooth infection, or in your 30s or 40s of cancer, or any random age of an injury.
People in rich countries live much longer (and healthier) than people in poor countries because of access to modern medicine.
So apparently you think people shouldn't have access to any medical services?
The entire medical (and dental) profession is all about keeping you from dying when you're "supposed to". You're supposed to die in your teenage years of a tooth infection, or in your 30s or 40s of cancer, or any random age of an injury.
People in rich countries live much longer (and healthier) than people in poor countries because of access to modern medicine.
So apparently you think people shouldn't have access to any medical services?
Our ancestors probably also had to put up with people like you trying to prevent them from making fires because night is the great equalizer and everyone should sleep when it's dark or some other nonsense.
I feel miserable just trying to imagine why a person would think this way. I'm grateful I don't have this kind of psychology.
I feel miserable just trying to imagine why a person would think this way. I'm grateful I don't have this kind of psychology.
That's fine, you and your ilk can get old on your own, suffer from the degradation of health and consequently quality of life caused by aging, and eventually die from old age, we won't stop you.
The rest of us will support the relevant research, and use the results to remain young or to be young again, possibly lasting for millennia.
The rest of us will support the relevant research, and use the results to remain young or to be young again, possibly lasting for millennia.
Sounds like hell on a dying planet where more people keep coming and no one leaves.
(Dying from the point of view of being about to sustain human life)
Unless of course we have magically conquered space travel too.
(Dying from the point of view of being about to sustain human life)
Unless of course we have magically conquered space travel too.
> Unless of course we have magically conquered space travel too.
If everyone sticks around, they can help solve the problem. If people don't die, maybe they'll be forced to care for the planet instead of spoiling it for the next group.
If everyone sticks around, they can help solve the problem. If people don't die, maybe they'll be forced to care for the planet instead of spoiling it for the next group.
I have a feeling we'll both be worm food by 80 or 90. The difference being my ilk had a better appreciation for time, while yours thought they'd live forever.
Do you really think it makes that much difference, day to day?
Because if better appreciation just means you're on the right side of an argument that very rarely comes up, then your life quality is the same.
Because if better appreciation just means you're on the right side of an argument that very rarely comes up, then your life quality is the same.
Contrary to the person you're responding to, I think it does make a large impact on the day to day. It's going to drive very different philosophies of life. One obvious embodiment of this would be on fertility. One who ignores, let alone denies, their own mortality is going to, on average, a different perspective on fertility than somebody who accepts their own imminent mortality. And these sort of things can often sort of snowball into impacting many other issues in life, in very significant ways.
Day to day, not at all. Just more generally. How many times have we heard 'I wish I'd visited my X more before they died.' Timelines and sense of mortality force you to think about such things.
It's definitely not about taking solace in winning some inane argument. I won't be celebrating my death, nor yours, as some kind of win.
It's definitely not about taking solace in winning some inane argument. I won't be celebrating my death, nor yours, as some kind of win.
You think the problem of aging cannot be resolved?
Aging has long been characterized. We understand in which ways degradation happens, and no new ways have been found for several decades. There aren't that many; They can be tackled, one by one.
We have an assortment of tools today that weren't available a mere 20 years ago, and it is our moral imperative to do this research.
There's more people suffering from aging and the conditions it does cause than any other health issue. All of us will eventually degrade, suffer and perish if nothing is done about it.
Improving the quality of life of our aging population by supplementing the shortcomings of metabolism (and thus un-doing aging) is the target.
Longevity would be a byproduct of this.
Aging has long been characterized. We understand in which ways degradation happens, and no new ways have been found for several decades. There aren't that many; They can be tackled, one by one.
We have an assortment of tools today that weren't available a mere 20 years ago, and it is our moral imperative to do this research.
There's more people suffering from aging and the conditions it does cause than any other health issue. All of us will eventually degrade, suffer and perish if nothing is done about it.
Improving the quality of life of our aging population by supplementing the shortcomings of metabolism (and thus un-doing aging) is the target.
Longevity would be a byproduct of this.
You're entitled to have opinions about your own life. When you start using your values to try to decide how long I should live mine... this is why you get hostile reactions.
> Time is the great equalizer
Yes, totally, we all get to live exactly the same amount of time, so it's perfectly fair. Also that fixed term life deal is the perfect amount of time by definition, so we should never, ever try to change it.
> Time is the great equalizer
Yes, totally, we all get to live exactly the same amount of time, so it's perfectly fair. Also that fixed term life deal is the perfect amount of time by definition, so we should never, ever try to change it.
Yes, your reaction was covered under the 'quit trying to control my life' clause. Not sure what else is being added here.
> Not sure what else is being added here.
A challenge to your assumption that there is an implied system and that said system is somehow fair in its current state. It's nonsense.
A challenge to your assumption that there is an implied system and that said system is somehow fair in its current state. It's nonsense.
Would you agree that for every year added to your life, a year should also be added to all those in third world countries?
My main argument is against the wealthy buying time that others cannot. This is why I'm not against say, penicillin and such.
If you feel that is a bad argument, please explain why. If you feel it's fair, then I think we may agree. I'm not against humanity living longer, I'm against some select few doing so.
My main argument is against the wealthy buying time that others cannot. This is why I'm not against say, penicillin and such.
If you feel that is a bad argument, please explain why. If you feel it's fair, then I think we may agree. I'm not against humanity living longer, I'm against some select few doing so.
I don't disagree with that at all, in principle.
"I should get to live longer and everyone else can rot" would be a particular sort of evil.
However what I don't agree with is going from there to "unless everyone can have it, noone can". An awful lot of medicine is not (yet) available to everyone in the world, and while I think it should be, and we should work towards every last human being having access to free, socialised healthcare of the highest quality, you won't find me calling for denying cancer treatments to those in wealthy nations because other nations can't foot the bill.
"I should get to live longer and everyone else can rot" would be a particular sort of evil.
However what I don't agree with is going from there to "unless everyone can have it, noone can". An awful lot of medicine is not (yet) available to everyone in the world, and while I think it should be, and we should work towards every last human being having access to free, socialised healthcare of the highest quality, you won't find me calling for denying cancer treatments to those in wealthy nations because other nations can't foot the bill.
Well, the other side of the coin is whether those folks even want to live longer.
We have gotten so used to being generally blind to essentially slave labor to support our lifestyles. Is it fair if we double our lifespan while those stuck in poverty making our products don't, or perhaps don't even want to?
We have gotten so used to being generally blind to essentially slave labor to support our lifestyles. Is it fair if we double our lifespan while those stuck in poverty making our products don't, or perhaps don't even want to?
I don't think very much is fair about anything in that picture, but I also don't think we should hold back advances or treatments while we work that out, nor do I think that it's particularly useful to relate those two phenomena specifically, you could as well say "Is it fair we use jet-skis while those stuck in poverty making our products have such a poor quality of life? Is it fair to use iphones while those stuck in poverty making the iPhones have such a poor quality of life?", and to be honest I'm slightly inclined to say "no" to that last one...
Significant longevity treatment is likely to be highly disruptive to our society in many ways, but I don't think that we should either fall for the fallacy that we can accurately predict those ways, nor succumb to the idea that we won't or can't adapt positively.
Significant longevity treatment is likely to be highly disruptive to our society in many ways, but I don't think that we should either fall for the fallacy that we can accurately predict those ways, nor succumb to the idea that we won't or can't adapt positively.
It doesn't bother me.
Every single one of my ancestors for the last 3.5 billion years has died. It is part of existence.
50, 60, 100 more years? Great! Then I can pile on knee, hip, back, and wrist regeneration surgeries. Then extensive therapy to keep my brain from degrading. Also new teeth and corneas. Oh and the heart is going to need a lot of work if it starts beating for twice as long as it was designed to. Plus constant maintenance for the skin as it soaks up an entire second lifetime's worth of UV.
Just a never-ending cycle of expensive, likely painful, time-consuming all-consuming patches on the body to delay the inevitable.
Just kill me already.
Maybe eventually they'll find a path to immortality.
That would be even worse. I imagine the joy would drain out of sunsets if you've seen a billion of them, with them being as noteworthy as every time your eye blinks.
Every single one of my ancestors for the last 3.5 billion years has died. It is part of existence.
50, 60, 100 more years? Great! Then I can pile on knee, hip, back, and wrist regeneration surgeries. Then extensive therapy to keep my brain from degrading. Also new teeth and corneas. Oh and the heart is going to need a lot of work if it starts beating for twice as long as it was designed to. Plus constant maintenance for the skin as it soaks up an entire second lifetime's worth of UV.
Just a never-ending cycle of expensive, likely painful, time-consuming all-consuming patches on the body to delay the inevitable.
Just kill me already.
Maybe eventually they'll find a path to immortality.
That would be even worse. I imagine the joy would drain out of sunsets if you've seen a billion of them, with them being as noteworthy as every time your eye blinks.
What if its not constant patches and repair work, but something that slows the degradation entirely so you end up with less health issues up until the point you get cancer and die anyway. But you enjoyed more of that time fitter and healthier.
I would be very happy if my body can stay young and not necessarily live longer. That's what anti-age means right? Not pro-long your life necessarily, but to live younger, so I don't have to care about my knee problem when exercise.
> I imagine the joy would drain out of sunsets if you've seen a billion of them, with them being as noteworthy as every time your eye blinks.
So you can imagine that rather than see another sunset, you'd die?
You can imagine a state of being where you become so jaded, so incurious, that nothing can pique your interest any more, that interpersonal relationships would be better off terminated with biological death than continued, that learning, travel, discovery all lose their meaning and value?
Honestly, as with many of these comments, I feel it says more about your present life than those who would like to live longer or indefinitely.
And I certainly know people in their 70s who are not ready to settle down and be fitted for a coffin yet, even if their bodies are starting to seriously disagree. I don't imagine they would turn down the chance of a few more decades of relative fitness.
So you can imagine that rather than see another sunset, you'd die?
You can imagine a state of being where you become so jaded, so incurious, that nothing can pique your interest any more, that interpersonal relationships would be better off terminated with biological death than continued, that learning, travel, discovery all lose their meaning and value?
Honestly, as with many of these comments, I feel it says more about your present life than those who would like to live longer or indefinitely.
And I certainly know people in their 70s who are not ready to settle down and be fitted for a coffin yet, even if their bodies are starting to seriously disagree. I don't imagine they would turn down the chance of a few more decades of relative fitness.
It's more about "die young, as late as possible" than live forever
>50, 60, 100 more years? Great! Then I can pile on knee, hip, back, and wrist regeneration surgeries. Then extensive therapy to keep my brain from degrading. Also new teeth and corneas.
>Just a never-ending cycle of expensive, likely painful, time-consuming all-consuming patches on the body to delay the inevitable.
So I take it you never visit a doctor or dentist? After all, going to the doctor to get that mole checked for cancer, or getting your teeth drilled to prevent an infection that kills you is unnatural.
>Just a never-ending cycle of expensive, likely painful, time-consuming all-consuming patches on the body to delay the inevitable.
So I take it you never visit a doctor or dentist? After all, going to the doctor to get that mole checked for cancer, or getting your teeth drilled to prevent an infection that kills you is unnatural.
Anti-aging by necessity also means solving the common causes of death and your body falling apart, not just letting them happen but somehow preventing them from killing you.
I don’t think I’m important enough for it to matter, and I’m fairly sure the fact I will die is a significant component of what makes the brief time I have so valuable.
An enormous amount of resources are wasted on treating specific, often rare, individual age-related conditions that doesn't efficiently transfer to other conditions. Clearly, people are hurting and it'd a net positive to society to treat the single underlying cause, and save the resources expended on everything else, for an equal if not improved overall health outcome.
Even if you don't consider yourself important to the world, surely you are important to yourself. At least I as an atheist consider my limited time alive here— conscious and healthy— to be infinitely valuable to me personally as it's really all that I have. And I think if your life isn't valuable to you in the same way, there's something wrong. Hence, extending it is a worthwhile goal.
Longevity research is difficult and it's not as if a breakthrough improving our lifetime by an order of magnitude is around the corner. So, I see little risk in ambitious research that'll probably only yield humble results anyway, at least until we're reaching 200 years old.
Even if you don't consider yourself important to the world, surely you are important to yourself. At least I as an atheist consider my limited time alive here— conscious and healthy— to be infinitely valuable to me personally as it's really all that I have. And I think if your life isn't valuable to you in the same way, there's something wrong. Hence, extending it is a worthwhile goal.
Longevity research is difficult and it's not as if a breakthrough improving our lifetime by an order of magnitude is around the corner. So, I see little risk in ambitious research that'll probably only yield humble results anyway, at least until we're reaching 200 years old.
> Even if you don't consider yourself important to the world, surely you are important to yourself. At least I as an atheist consider my limited time alive here— conscious and healthy— to be infinitely valuable to me personally as it's really all that I have.
I agree with this completely, so long as it doesn’t actually cause problems for younger people born into the world. At the moment it’s arguably a good thing that we die and let new generations have their shot at things. I’m only 37 and already excited to see what people in their teens manage to accomplish before I die. By the time the they’re full swing and doing cool stuff, I’ll probably be looking for my keys for a car I haven’t owned for 20 years in a bingo hall. No one will need more of me.
Fundamentally though I believe our time is rarely spent as well as it could be, and fixing that might be best to come first. Should I live longer if I don’t cherish it? Should I want more days when I’ve admittedly wasted many? Perhaps the best thing I could do is learn to use the time I have to its fullest.
And of course, I go to great lengths to protect my health and lifespan — I want to live as long as I reasonably can, and I want to be able to enjoy it. I don’t think for a second that I should prolong that to any degree which begins to hinder the opportunities and possibilities of younger people, though. Maybe that sounds crazy. I just don’t think I matter more than another person, just like me, wanting all the same opportunities in their own life. I guess I don’t believe old people should be in the way of young people fully living their lives.
As long as that’s not happening, sign me up. Until then I’d like to learn to use my time more wisely. On the Shortness of Life totally transformed how I think about longevity and lifespan extension in general. It seems to pale in importance compared to the practice of living better to begin with.
I agree with this completely, so long as it doesn’t actually cause problems for younger people born into the world. At the moment it’s arguably a good thing that we die and let new generations have their shot at things. I’m only 37 and already excited to see what people in their teens manage to accomplish before I die. By the time the they’re full swing and doing cool stuff, I’ll probably be looking for my keys for a car I haven’t owned for 20 years in a bingo hall. No one will need more of me.
Fundamentally though I believe our time is rarely spent as well as it could be, and fixing that might be best to come first. Should I live longer if I don’t cherish it? Should I want more days when I’ve admittedly wasted many? Perhaps the best thing I could do is learn to use the time I have to its fullest.
And of course, I go to great lengths to protect my health and lifespan — I want to live as long as I reasonably can, and I want to be able to enjoy it. I don’t think for a second that I should prolong that to any degree which begins to hinder the opportunities and possibilities of younger people, though. Maybe that sounds crazy. I just don’t think I matter more than another person, just like me, wanting all the same opportunities in their own life. I guess I don’t believe old people should be in the way of young people fully living their lives.
As long as that’s not happening, sign me up. Until then I’d like to learn to use my time more wisely. On the Shortness of Life totally transformed how I think about longevity and lifespan extension in general. It seems to pale in importance compared to the practice of living better to begin with.
> surely you are important to yourself.
Depends on how depressed a person is I guess. ;)
Depends on how depressed a person is I guess. ;)
Is your life more valuable the briefer it is?
If 1/x where x is the current age, then yes. I say it as a joke but makes me think why more mundane experiences on my childhood stuck more than profound ones on later life.
This question/answer is the standard fallacious response to anybody talking against the anti-aging current.
Some people may indeed prefer to die, some people may be religious or whatever, but most people doing the criticism just give extremely low prior probability to not dying due to some technological/medical advance (during their lifetimes at least), so they consider obsessing with something that is virtually impossible for the hope that it will happen a waste of time, of the finite life they have.
Then it boils down just to whether one is curious about it, or is curious about any other X subject.
Some people may indeed prefer to die, some people may be religious or whatever, but most people doing the criticism just give extremely low prior probability to not dying due to some technological/medical advance (during their lifetimes at least), so they consider obsessing with something that is virtually impossible for the hope that it will happen a waste of time, of the finite life they have.
Then it boils down just to whether one is curious about it, or is curious about any other X subject.
For me the anti aging, immortality thing is funny because I think it has been solved for most species: it is called reproduction. Actually surviving is reproducing.
If anti aging proponents spent as much time trying to reproduce and making sure their offspring were fit to continue their bloodline with good education it seems to me a good outcome. That is why the education of my children is important: the imprint of intellect self after I imprinted my bodily self in their genes.
One could argue, but “hey ptsneves your children are not you thus you will unavoidably going to be eliminated from existence”. And I say, “it is ok and part of physical existence. I accept it.“
Evolution found it worthwhile to have sexual reproduction, meaning clones are a bad fit for eco system disturbances.
Evolution also found it fit to restart the cycle from scratch even if it meant an individual would lose experience or ecosystem optimality. This is to protect again local optimae , which is a great path to extinction.
The extent of these 2 premises is such that the apex predator on earth reproduces sexually and has a limited life span. Maybe that is survival bias but I think there are good causation ideas behind them.
With the above if I really want to be immortal and have my legacy preserved robustly I should use the current system: reproduction with a good emphasis on descendant upbringing and according to my experience. Again, even if I am great in my current eco system I do not presume this experience will work with eco system disturbances, so I accept evolutionary bargains and have children with a partner I believe will fulfil my bodily destiny the most resilient way possible.
I even wanted to start a religion where propagation of one’s self through dedication to offspring and community is central. I am tired of a society ruled by geriatric concerns[1]. (I say this as mostly a joke of course, I have more than enough work raising my children much less dabbling in other peoples lives)
Ps: none of what I wrote invalidates improvements on longevity. It is just that we already have a basic system for propagation in time.
[1] I know extremely young demographics make for crappy countries and quality of life.
If anti aging proponents spent as much time trying to reproduce and making sure their offspring were fit to continue their bloodline with good education it seems to me a good outcome. That is why the education of my children is important: the imprint of intellect self after I imprinted my bodily self in their genes.
One could argue, but “hey ptsneves your children are not you thus you will unavoidably going to be eliminated from existence”. And I say, “it is ok and part of physical existence. I accept it.“
Evolution found it worthwhile to have sexual reproduction, meaning clones are a bad fit for eco system disturbances.
Evolution also found it fit to restart the cycle from scratch even if it meant an individual would lose experience or ecosystem optimality. This is to protect again local optimae , which is a great path to extinction.
The extent of these 2 premises is such that the apex predator on earth reproduces sexually and has a limited life span. Maybe that is survival bias but I think there are good causation ideas behind them.
With the above if I really want to be immortal and have my legacy preserved robustly I should use the current system: reproduction with a good emphasis on descendant upbringing and according to my experience. Again, even if I am great in my current eco system I do not presume this experience will work with eco system disturbances, so I accept evolutionary bargains and have children with a partner I believe will fulfil my bodily destiny the most resilient way possible.
I even wanted to start a religion where propagation of one’s self through dedication to offspring and community is central. I am tired of a society ruled by geriatric concerns[1]. (I say this as mostly a joke of course, I have more than enough work raising my children much less dabbling in other peoples lives)
Ps: none of what I wrote invalidates improvements on longevity. It is just that we already have a basic system for propagation in time.
[1] I know extremely young demographics make for crappy countries and quality of life.
Do you see more discussion of anti-aging on HN than you see discussion of major diseases?
I don't see more of it. And I think it's fair to talk about aging as much as cancer, for example. They're both very difficult fights to claw back months or years, but we can figure out how to slow the progress and cure specific instances.
If we could extend life expectancy by two years that might beat covid in impact. Isn't that worth significant research and discussion?
It's not just people idly wanting to live a million years.
I don't see more of it. And I think it's fair to talk about aging as much as cancer, for example. They're both very difficult fights to claw back months or years, but we can figure out how to slow the progress and cure specific instances.
If we could extend life expectancy by two years that might beat covid in impact. Isn't that worth significant research and discussion?
It's not just people idly wanting to live a million years.
>And I think it's fair to talk about aging as much as cancer, for example.
I agree with the underlying argument, but I must note: Cancer gets more likely with age, and the mechanisms that enable it are considered one of the (few) groups by which aging is characterized.
All these groups are co-morbid, so any progress in un-doing the damage of aging will also help with cancer.
I agree with the underlying argument, but I must note: Cancer gets more likely with age, and the mechanisms that enable it are considered one of the (few) groups by which aging is characterized.
All these groups are co-morbid, so any progress in un-doing the damage of aging will also help with cancer.
I don't know man my parents just spent the first few years of their early retirement caring for my grandma who is now in the final phase. It's not like you just won't be there one day. It also costs others a lot of time and effort, money et cetera.
There are a lot of men in tech with lots of money, engineering expertise that they believe will carry over to biology, and a fear of becoming old and irrelevant.
Ding ding ding.
There are many avid sci-fi fans here. So it's likely as much to do with piqued interest (scientific or philisophical), as it is to do with not wanting to die.
Someone who loved reading Time Enough for Love, or Permutation City, is probably going to be interested in the subject.
Someone who loved reading Time Enough for Love, or Permutation City, is probably going to be interested in the subject.
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How are you going to learn all the essential Javascript frameworks in time if you die before you reach your first few centuries of age?
It's simple. We want trusted individuals and knowledgeable debate on the topic, especially for one so controversial. And yet, this entire thread is now revolving on your meta commentary on the topic. Very disappointing.
It doesn't pop up nearly as us fans would like, and I barely see it once a month on here.
It doesn't pop up nearly as us fans would like, and I barely see it once a month on here.
To be fair, the other most likely source you’d receive anti-aging news from, r/science, is hands down the worst moderated community on the internet and I wouldn’t put it past them to bury such news by their own whims.
We all want to live long enough to witness the singularity. <wink>
Thanks for that, never heard of it before - there is a 90 min radio adaptation archived here:
https://archive.org/details/john-wyndham-trouble-with-lichen
https://archive.org/details/john-wyndham-trouble-with-lichen
The odd thing is, HN is also obsessed with early retirement. You’d think people would’ve learned the lesson of One Foot in the Grave.
To me it just signals a lack of emotional maturity
I mean, HN has more than a few Peter Thiel fans..
I regularly see anti-aging discussion/news here and on 4chan's /sci/ board (aka the flat earth and electric universe debate forum.) Make of that what you will.
If you want to start down the rabbithole (SENS talks can be trusted and are good, well-backed by science, etc etc. Have been derailed by some drama recently, but still, they've really done a lot) then you can start by going to the rejuvenation roadmap: https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/
A little further (Aubrey de Grey, from SENS originally): https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_ag...
If you want to lose 4-5+ hours (minimum -- think TVTropes level of rabbithole addiction here), then here is your next free joyride. It's a fun one, I've been pretty interested in it as it's continued to have developed. Have fun reading the saga: https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbu...