Hacker News Reader

Comment by maxander | Hacker News Reader

Since it seems like the upshot of all of this is that Katcher is claiming to have discovered a set of signalling molecules which, when injected, rejuvenate tissue and presumably lengthen life, it runs into one of the most fundamental objections that can be leveled at theory of aging (or cure thereof): of the billions of humans that have existed, how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment? In the case of this proposal this sort of objection is particularly strong, since (though the blog post is silent as to what the treatment is) it's given that they are fractions from blood, so they're substances which the body produces in some quantity anyway, and which are sufficiently non-dose-specific that Katcher, with limited resources, could devise a reasonably effective regimen.

Parabiosis is one of the most striking (and just weird) phenomena in aging research, so efforts to understand what's going on with it are liable to bear interesting fruit. I'm just pointing out that there's good reason to doubt that this particular "breakthrough" is the "cure."

View on HN

At risk of sounding absolutely insane:

There's probably no way to prove that this hasn't happened. Anyone who realizes they're not aging normally would likely have taken on a new identity elsewhere for fear of:

1. being burned at the stake

2. being trialed in repeated experiments

3. being deified, and then subsequently being burned at the stake.

---

I realize my comment sounds like a joke, but I'm entirely serious. If you or I found out we're not aging normally and look e.g. 25 by the time we reach 40, or 30 by the time we reach 45, would either of us remain in our current lives?

There are other things that can cause similar effects. Many people look “younger” than their age.

https://en.wikipedia.org/wiki/The_Man_from_Earth

One of the only movies that remains intriguing throughout despite being basically a single conversation.

Just don't look up the sequel.

What about "My Dinner with Andre?" That's exactly a single conversation.

And so is, mostly, "Rope."

I happen to love certain niche movie genres, which happens to include "dinner party movies". Feel free to list some recommendations, if you like "people talk in a room" movies.

Some of my favories:

    Coherence (scifi)
    Garden Party (sleazy young adult Los Angeles drama)
    Murder Party (low budget horror comedy)
    How English sounds to non-English speakers (youtube)
    Circle 2015 (scifi)

The Invitation (2015 film)

12 Angry Men. My Dinner with Andre. Steve Jobs (a stretch, but much more a play than a movie).

There's some play adaptations which have few characters and mostly dialogue: Carnage, Who's Afraid of Virginia Woolf, Glengarry Glen Ross

Linklater's "Before" trilogy is also heavily dialogue-based, but the there are multiple locations.

El método (2005) is a really good take on corporate/personal dynamics.

https://www.imdb.com/title/tt0427582/

"How About Adolf?" (2018) [0].

"Perfect Strangers" (2017) [1].

[0] https://www.imdb.com/title/tt7477310/

[1] https://www.imdb.com/title/tt6101820/

Not exactly a dinner party movie, but Sleuth (1972 and also the 2007 remake) is a good one.

The Big Kahuna (1999) ("the majority of the film takes place in a single hotel room, and nearly every single line of dialogue is spoken by one of the three actors.")

Exam (2009) is another good single-room film.

I love those kinds of movies. It's a Disaster (2012) is a good watch.

At the risk of the suggestion being a spoiler in and of itself, the movie The Man From Earth is basically about this topic.

It's also entirely possible that they just look younger, but aren't given much more of a lifespan because there's other issues with such a treatment. So someone that just ages well but ends up dying of otherwise natural looking causes and a typical age.

Might I recommend the "The Man from Earth" (https://www.imdb.com/title/tt0756683/). Definitely worth checking out.

It's a low budget film, but I agree that it's worth watching.. especially for the socio/psychology elements.

One of my most favorite sci-fi movies explores this idea [0]. It's very intriguing and quite entertaining.

[0] https://en.wikipedia.org/wiki/The_Man_from_Earth

Was going to also post the same thing. It too is one of my favorite sci-fi movies.

I just commented before seeing your mention of it.

Although I didn't realize until I commented that Jerome Bixby the author of The Man From Earth was also a Star Trek writer.

Oh yes. I met them in person a while back [0]. Super nice people.

[0] https://twitter.com/synopsi/status/1188295183130955778?s=21

He wrote the episode Requiem for Methuselah, which has an almost identical premise.

I've met people who look 25 but are actually 45. A few of them, actually. It's on the extreme end of the bell curve but it happens.

As for more extreme cases, I could believe that a few people discovered that they weren't aging and hid it, but not more than a few people, especially in modern times. Switching identities isn't exactly easy and the probability of every one of them successfully carrying it out gets exponentially suppressed as the number of people increases.

I guess one would when they start approaching 80 and looking as 35.

Given how much people focus on looking youthful, it's probably reasonable to assume that appearing youthful has historically been advantageous, from a reproductive point of view. Which would lead such a mutation to spread pretty rapidly throughout the population.

Probably confounded by the social dynamics of human groups. There also isn't any evidence that it would extend reproductive lifespan either.

> There also isn't any evidence that it would extend reproductive lifespan either.

FWIW, it doesn't need to do this. It just need to result in more surviving children and grandchildren. Looking 5-10 years younger when you're a female between the ages of 25 and 40 could A) get you access to a higher status mate who can better provide for your children, and/or B) keep your mate more interested in you, reducing the likelihood that they will continue to provide for the children you have with them.

Someone I work with looks very youthful for their actual age, and that isn't always a good thing.

When the team went on an offsite morale event jet skiing, he was told by the proprietor that he couldn't participate because their policy requires you to be at least 16 years old. He was 27 at the time. He never lived that down with his peers. When he tries to go to a bar with friends, he's sometimes accused of trying to pass off a fake ID. These experiences are deeply embarrassing for him.

Imagine trying to get promoted to a senior director position at a company while looking like you are fresh out of college. In that case ageism takes a different meaning.

I'm only 23, so I understand that I am young, but looking young is, without a doubt, a serious disadvantage when it comes to people trusting in your ability.

I recently worked on overhauling the reporting system for one of the largest police departments in the US, and every step along the way I was asked who was in charge, how did I enter the workforce so young, how I got an internship while attending high school (I had already graduated college), etc. I even got those types of comments from other employees at companies where I worked full-time. Of course, I don't really have the luxury of getting too offended by it all the time, otherwise I'd be really bitter, but the classic "Oh well you'll be glad you look young when you're older" gets tiring.

I always looked about 5 years younger than my age. It sucked when I was young. At 40 it’s not the worst quality, but it also doesn’t help much. So I look 35, big whoop. I did discover wearing my hair long in my 20s made me look a bit older (eh, more like my age). Might try modifying your look.

Absolutely, just dressing differently and changing a few things has helped. Facial hair is a big one. I'd rather look young than be balding at 23 like some of my peers.

Right!? I found dressing “older” actually made me look younger. It looked like I was pretending to be grown up. I kind of embraced a rock/slacker look in my 20s and that worked best. These days I just do the dad look. That works fine. Best of luck out there!

Wear a suit? That thing buys a lot of deference.

You have to be careful not to come across like "a suit" in the engineering circles, it's a tricky balance, but it's worth it.

Yeah, I have experienced this as well before hair loss started up in earnest. Not really fun walking around with your partner of the same age and someone thinking she's your mom (she started graying early).

I think people age at different rates.

My Dad is in his mid 80's and plays four hours of sports a day, or at least he was before the pandemic hit.

When I was in my mid-20's I had to impress the hell out of potential clients to get work, as I looked like I was 15, and girls my own age wouldn't look at me as I was too young. I never drank, so bars weren't an issue. When I was in my early forties, 15-20 year old girls were still coming on to me. I will be 50 next year, and I finally look like I'm in my 20s or 30s, and still get those looks from University-aged girls whenever I venture where they hang out.

A couple of years ago, my now 43 year old partner was mistaken for her teenage doppelganger and asked to the high school prom by three different boys while walking home from work.

It was annoying earlier, but now I look forward to turning out to be one of the immortals.

> A couple of years ago, my now 43 year old partner was mistaken for her teenage doppelganger and asked to the high school prom by three different boys while walking home from work.

Pretty sure I saw this movie in the 80s.

One thing to remember is that people don’t have perfect vision either. As long as you are not out of shape or have sagging skin or gray hairs, people will not be able to clearly see any wrinkles or other textures in skin that would give away age.

In general I’ve seen a lot of people that look young for their age but when looking at their skin up close on their face, neck or hands it gives it away. Women are also at an obvious advantage through their use of makeup.

>When I was in my early forties, 15-20 year old girls were still coming on to me. I will be 50 next year

I've read that when Scott McNealy met his future wife (they married when he was 40) she thought that he was a Stanford undergraduate.

Here's a response that he can use when people comment on his youthful appearance.

"You look so young."

"I have this portrait in my attic."

I appreciate the dorian gray reference :)

A friend of mine also has this issue. She just turned 30 but looks like she could be a teenager, or perhaps a uni student.

We did a Dexa scan a few months back and it put her age based on body composition at 14.

She gets annoyed about it sometimes as she feels people don't treat her seriously. Because of this she's quite conscious of what she wears, and how she presents herself.

For anyone curious you can find her on youtube - search "Good Paleo Life"

I am 34, and people always say I look 23. In my last job, upon meeting me, people asked if I was a student (intern) or just graduated.

It was nice. I can't grow facial hair though so I have no choice. What worries me is when I'm 45, I'll look like the world's oldest 30 year old or something.

I'm 26 and but I look much younger (as long as I shave my beard). I regularly have to show my ID when buying alcohol for instance (which you can do with 16-18 in my country).

It's rather fun for me and I enjoy these kinds of interactions. Can't say it really ever hindered or embarrassed me in any way.

I suspect that if those people who feel embarrassed because they look young were looking older, they'd find something else to be embarrassed about. It's easy to find any number of shortcomings with yourself.

He should grow a beard then. It probably helps.

Probably, yes. I turn 40 this month, and was recently told by someone who just met me that I look 25. What exactly am I supposed to do differently now?

Ignore benign random behaviors and continue to apply your agency as you see fit?

I'm sorry, my programming is limited. I'm unable to answer your question.

This is kind of obvious, but since you are asking: you have to quit your job, quit your hobbies, delete your social media accounts, go out into the desert and spend 15 years seeking the true meaning of life.

I recently returned to a workplace I left 15 years ago. There are a substantial number of staff still there who are around my age - early middle aged. Many look very similar, but what took me by surprise - as I've never studied a large group of aging people over a decade plus - is their skin. Superficially features, hair, body weight, etc., hadn't changed but to a man (ie across everyone) they all have "aged" skin.

So, if you want to tell if someone is 25 or 40, maybe their skin will give it away?

this person exists--- his name is Jared Leto.

I was thinking Jon Bon Jovi.

Interestingly he is vegan. Many people I know that follow a plant based diet look suspiciously younger than the norm (I get the same comments often too). Causation or correlation - who knows.

Probably can't chalk it to that - I mean, Keanu Reeves is ageless as well and he's not.

haha yup!, I feel like all the people I know who look relatively young for their age don't eat a ton of meat or processed foods, also are extremely active both physically and mentally with work or other endeavors. Sitting around watching TV doing nothing in retirement is a sure way to early death.

This implies a sort of binary between "normal" aging and vampire-like eternal youth, but if these mutations do exist within the population, their practical effects are likely far more nuanced due to confounding factors.

There would almost certainly be a continuum, perhaps following a power law. The top quartile might be the "40 not looking a day over 25," while the top 0.1% might be true Dorian Greys.

regarding mutations, perhaps they are just confined to certain physical systems. The reason I bring this up is my mother-in-law has brownish hair with not a single grey hair, she does not dye her hair and is about to turn 70. Her mother also has barely any grey hair and is in her 90's, this to me is extremely strange as people in my family get alot of grey in their 40's and most get grey at least by 50ish.

> If you or I found out we're not aging normally and look e.g. 25 by the time we reach 40, or 30 by the time we reach 45, would either of us remain in our current lives?

I was routinely told I looked 25 at the age of 45, and can assure you I felt no need to start accumulating secret identities.

A surprising number of people have taken my comment rather personally.

Well, you know, the way you wrote the comment, it kind of invited us to take it as personal - as applying to ourselves.

My personal experience led to that assumption; I've never guessed anyone's age wrong by 15 years, hence the example. Sorry it hit you the way it did; wasn't my intent.

I don't think we took it "personally" in a way that calls for an apology. I don't think anybody felt accused or anything - just that we are responding literally, noting that some of us are in those circumstances, and aren't reacting the way you said. That's all I meant when I said you invited us to take it personally. I did not at all mean that you gave us grounds for feeling accused or defensive. (But thanks for the non-defensiveness of your reply - this conversation could easily have blown up with you feeling accused by my post, and I would not have known why, because I didn't mean it that way at all - which may mean that I wrote it badly.)

Internet is full of these stories, I believe none. For one, even if there are people who look younger (say, Selena Gomez, or Lucy Liu) even them cannot pass to be 10+ years younger than they are, after looking at them in person. Have you actually met a 30+ year old person who could pass consistently as a teenager? I have never met one. The second thing is that if you are "routinely" told that you look XX or YY years old , either you are going around people telling your actual age, or they are being gracious in their compliment. You dont approach a teenager to tell them that they look young.

These responses happen after people encounter me first, then see my kids come up to join the conversation (in their 20's) getting introduced as my kids, at which point the person I'm talking with realizes I am way older than they thought and they freak out. "Routinely" doesn't mean daily, but it does mean it happens often enough to be a thing.

I've gotten that from time to time. My oldest is turning 22 this year. When people hear that, they do a double take and say, "wow, you're not old enough to have a kid that old," to which I agree. I had her at 15 - a bit young to have a kid that age indeed.

I did meet a Taiwanese woman who I thought was a teenager but was actually in her 30s. It could be because I am not asian myself and have difficulty recognising distinctive features of asians, but she said that her friends in Taiwan told her the same all the time.

I’m almost 30 and I know I look like a teen because salespeople who knock on my door ask if my mom is home and flight attendants don’t want to let me sit next to the emergency door (you have to be FIFTEEN for that!). I can buy child tickets to things without a question asked. Of course celebrities don’t really look like teenagers, because they’re meant to look attractive. Real people who look young look like gangly awkward teens :)

That artist that survived both the Spanish Flu and COVID is 107.

Go take a look at her photo.

This one? To be fair, this photo is back from when she was a youthful 102.

https://www.washingtonpost.com/local/at-107-this-artist-just...

But yeah, wow.

I once met a 102 year old man who lived alone in a big patch of private forest in BC that he bought in the '20s. He was still driving a car and doing jumping jacks.

Amazing. She looks like she's in her 70's, or early 80's at the worst.

I looked, and she's wearing an Ouroboros necklace.

"The Ouroboros, an ancient symbol depicting a serpent or dragon eating its own tail, has been said to have a meaning of infinity by depicting the cycle of birth and death. The Ouroboros eats its own tail to sustain its life, in an eternal cycle of renewal."

I'm 31 and can probably pass for a college senior if I dress the part. I still can't get my facial hair to connect and form a full beard.

Waiting for my deification now...

I think you should consider the boiling frog syndrome.

Not aging is as slow as aging, and by the time you realise and accept there is something special with you, everyone else around has already figured it out. Disappearing at that point might be a pretty conspicuous move "that guy [or woman, I wonder why all immortals must always be men... :)] who is 70 but actually looked thirty went missing".

Based on your comment, you will likely enjoy "The Boat of a Million Years", by Poul Anderson [0]. Needless to say, it's science fiction.

It's about a very small number of people who are immortal, in the sense they stop ageing at 25 (iirc). They can be killed like anyone else, but smaller damages do heal faster. Also, they never get sick. Some are thousands of years old, some less. Some smart, some not so much. How they handle their immortality is very interesting though. I won't spoil it for you though.

[0]: https://en.wikipedia.org/wiki/The_Boat_of_a_Million_Years

The Lords of Farmer's World of Tiers also stop ageing at 25 and are immortal unless killed, usually by other Lords. I loved that series when I was young.

Like in the Highlander.

I think the variation in “visual age” is too large for “look like 25 by the time we reach 40” to be an outlier.

Excessive smoking and UV light exposure can easily make a 25-year old look older than a healthy 50-year old who exercises regularly, uses sunscreen when they go out in the sun, and didn’t get scars from accidents.

That's pretty much the plot of the story The Man From Earth written by Jerome Bixby. He also wrote a similar story for the original Star Trek series.

The Man From Earth and its sequel are on Amazon Prime Video.

edit: I should have did a ctrl+f man from earth

It's a great show everyone seems to have seen it. I never knew about it until I saw it in my Amazon Prime Video suggestions.

I’d guess that one out of fifty times the person would not die prematurely, have the means and foresight, and then go on to do this; and that one out of two times their community, which they don’t part ways with, catches on and names them a god for a while.

Have you seen "The Man From Earth"?

Robert Heinlein had a whole universe where this was the case. A group of people had been bred to live as long as possible and hid it from the wider world for fear of being hunted down and used as lab rats. They end up fleeing to space when discovered.

Sounds more like vampire-fiction like historical realities. People were "burned at the stake" for heretical ideas and challenging church dogma, not for looking suspiciously young. And the examples we have of living persons being deified was generally because they acquired enormous power (roman emperors, pharaohs and so on) not because of looking particularly young for their age.

> Sounds more like vampire-fiction like historical realities. People were "burned at the stake" for heretical ideas and challenging church dogma, not for looking suspiciously young. And the examples we have of living persons being defied was generally because they acquired enormous power (roman emperors, pharaohs and so on) not because of looking particularly young for their age.

https://en.wikipedia.org/wiki/List_of_people_executed_for_wi...

Quite a number were burned for (obviously alleged) witchcraft. (grep page for 'burn')

That's where I derived that first bullet.

The actual charge was "maleficium", using magic to harm people. Things like poisoning also counted, although we wouldn't consider that magic today. The important point was the intention to cause harm.

Of course that was hard to prove or disprove, but we have examples of alleged witches accepting payment for harming/killing other people using whichcraft - like a contract killer. So at least the intention to cause harm was there in some cases.

There are numerous accounts of people having (alleged) supernatural abilities who was not persecuted, e.g ascetics surviving without eating for years and such. These were generally held in high regard, and could end up as saints.

Of course people could be accused for maleficium on really flimsy evidence so it could also hypothetically happen to the hypothetical slow-aging person just like it could happen to anybody else.

> There are numerous accounts of people having (alleged) supernatural abilities who was not persecuted, e.g ascetics surviving without eating for years and such. These were generally held in high regard, and could end up as saints.

> Of course people could be accused for maleficium on really flimsy evidence so it could also hypothetically happen to the hypothetical slow-aging person just like it could happen to anybody else.

Yep, hence points 1 and 3.

Thanks!

Well you only become a saint after you are dead and if miracles at your grave. So the risk of being saintified and then burned at the stake is not high.

My point was just that unusual aging patterns would not put you at any particular risk of being burned at the stake.

Andy Milonakis?

To take that further, most ancient myths from most cultures, have some kind of immortals in them.

And the same argument applies to true magicians btw.

When you could summon real magic, why should you reveal that to others?

(or care to claim a million dollar

https://en.m.wikipedia.org/wiki/One_Million_Dollar_Paranorma...

)

But I doubt it.

From a perspective of evolution, aging and dying and new borns, make sense, because the environment changes. And youth is able to adopt better to new changes.

I think this is unlikely because at some point there would be an large cohort of such persons; discipline among 25 year olds (your figure) regarding reproduction cannot be relied upon. :)

If you have not seen the movie The Man From Earth, I highly recommend it.

In the end, there can be only one!

>25 by the time we reach 40

The socially desirable scenarios like this aren't really the interesting ones. How about looking 5 when you reach 25?

It doesn't need to be the malicious.

Let's assume the mutation happens when the person is in their 20s, which would be ideal. If this occurred any time in history up to the 1800s, would you not still be likely to die of disease, cancer, or other injury? Life expectancy hasn't increased because we are better at slowing aging, it has increased because we are better at not dying of the things that kill us.

If the mutation happened invitro, did the child survive birth? If it did survive but never grew, it wouldn't reproduce, and may have been abandoned if it were too much of a burden.

There are many scenarios where this mutation could have occurred but was never passed on.

Or maybe they just died of other things. Pretty sure most people didn't die of old age historically.

Probably also worth noting that there are [stories of it happening before](https://en.wikipedia.org/wiki/Methuselah).

If you read Genesis most people mentioned there lived 100s of years. This most likely is an artifact of years corresponding to moon cycles (aka months) in the earlier parts of the Old Testament.

The novel "How to Stop Time" by Matt Haig is a recent addition to this genre, and is built on this very premise. It is a fun read. (And, unlike most "eternal life!" type books, has no vampires)

Assuming such a de-aging mutation had occurred, the countless other ways to die would eventually kill all such people. Setting aside the fact that - in a long enough time line - an illness, accident, combat, or some external factor independent of one's baseline physical condition would be guaranteed to get you, other natural effects of longevity like e.g. cancer incidence may not be reduced by <insert whatever this hypothetical mutation does> either.

Aside from that, it's only in the last millennium or so that we have record keeping that we could plausibly consider credible enough to prove the existence of such a person - in ages before that we have countless myths of immortality or unnatural longevity that we immediately disregard as fictional. So if Methuselah really had lived 969 years due to this mutation, we'd all be none the wiser!

>At risk of sounding absolutely insane:

>There's probably no way to prove that this hasn't happened. Anyone who realizes they're not aging normally would likely have taken on a new identity elsewhere for fear of:

>1. being burned at the stake

>2. being trialed in repeated experiments

>3. being deified, and then subsequently being burned at the stake.

---

>I realize my comment sounds like a joke, but I'm entirely serious. If you or I found out we're not aging normally and look e.g. 25 by the time we reach 40, or 30 by the time we reach 45, would either of us remain in our current lives?

1, 2 and 3 are very astute observations about human nature. ALL people who disagree on 1,2 and 3 are just naive in what they think human nature is. History repeats.

I think Jared Diamond had a similar argument that seems valid.

Roughly speaking, it boils down to the fact that you need 90 out of 100 subsystems in your body to be working. Your lungs, your heart, your skin, your brain, etc.

They interact, but each part also needs to work on its own for you to live. Every one of those systems can fail and leave you dead.

Since evolution only "cares" about you to the point where you bear children and raise them, what are the chances that it engineered ALL those systems to last FOREVER?

And then it created a single hormone to control every system and make them stop decaying?

Such a fantastic over-engineering can't occur purely by chance, 100 times over.

-----

In fact ANY mutation that decreased life expectancy but increased fitness during the reproductive years would be selected FOR.

So it seems possible you have multiple mutations that prevent you from living much longer than "expected".

(I'd even conjecture there's a sexual selection effect going on in the "live hard die young" people, like rock stars, athletes, etc. Their hormones are selected for "living on the edge", and that strategy has proven useful over millenia... i.e. a tendency toward self-destruction is not necessarily something that gets weeded out by evolution)

-----

That said I think it's definitely possible for some treatment to make someone who would have lived 60 years last until 70, or even 100. It's harder to imagine going from 100 to 200 (especially with productive life).

"Every one of those systems can fail and leave you dead. Since evolution only «cares» about you to the point where you bear children and raise them, what are the chances that it engineered ALL those systems to last FOREVER?"

Evolution works in small steps, over long periods of time (given the humans slow grow up process). Mutations in any of those systems may increase or lower the chances of such failure. Evolution takes care of both, albeit by a small margin. Currently, cause of death number one worldwide is the ischemic heart disease¹ (i.e. the famous "coronary"). Now guess what, there are genetic mutations that work on this out there already, one of them being the Gilbert's syndrome². Yes, forever is unattainable, but (humanity scale speaking) I'm glad having lived past twenty four and willing to take any blessing coming after.

"I'd even conjecture there's a sexual selection effect going on in the «live hard die young» people, like rock stars, athletes, etc."

I hope you're aware of survivor's bias here. Assume a lot more of those to be weeded out. Also, the stars made it not only because they were risk inclined but also because they they have that value they were recognized for.

I find the gradual improvement that one may gain having a bit of time to be a very useful edge over the young and inexperienced, in the game of life. Especially for a male (that is not that restricted by an inherent fertility age limit), this edge fits perfectly in the reproductive selection window you mention.

¹ https://www.who.int/news-room/fact-sheets/detail/the-top-10-...

² https://en.wikipedia.org/wiki/Gilbert%27s_syndrome#Cardiovas...

Sure, but the point is there would have to be a Gilbert-like mechanism for every subsystem of the body.

And Gilbert isn't "free" -- it comes at cost. The body is a machine, and engineering is full of tradeoffs.

People with high abilities in one area (geniuses) often have low abilities in others. Optimizing some protein for your heart isn't neutral for the rest of your body, etc.

The point about the stars is that evolution has "determined" that it can be optimal to take a ton of risks and die early than to live safely for 200 years (in some cases, of course evolution favors diversity too, which is why you see centenarians).

If you could get reward without risk, then it wouldn't work that way -- the "stars" would live forever creating great music and not drink themselves to death. But life is full of tradeoffs and reward involves risk.

evolution only "cares" about you to the point where you bear children and raise them

Humans are highly social beings that naturally live in large kin groups. Knowledge and culture form a huge part of our survival strategy. Who among us have the most knowledge and experience to pass on? Elders.

Take a look at the role of elders in traditional hunter/gatherer cultures. Huge importance. Is it not implausible that natural selection would favour increased life expectancy so that elders can maintain and transmit the group's body of knowledge?

Of course, that's what "raise" means. Grandmothers also raise their grandchildren -- google "grandmother effect" or "grandmother hypothesis".

I'm more talking about people who want to raise life expectancy from 100 to 200, not go from 70 to 100 (not sure where the original article fell on this).

70 to 100 is clearly possible and we've already gotten a long way there in the 20th century (antibiotics, etc.) The "problem" now seems to be that not everyone actually cares if they live that long... i.e. there are plenty of people who don't want to live to 100, and might not even if they maintained the health of a 60 or 70 year old.

>Since evolution only "cares" about you to the point where you bear children and raise them, what are the chances that it engineered ALL those systems to last FOREVER?

This sentence turn things into such an anthropomorphic way, to the point that the concept of evolution en engineering don't make sense anymore.

In the (scientific) evolution theories, evolution doesn't "engineer" life. It shapes life forms by environment constraints alone. And these constraints are in no appearing way optimized for fostering life, which appear more like an accidental byproduct. No conceptual framework nor any concern for conscious parsimony of implementation or sense of elegance are underlying evolution forces.

Indefinite youthfulness span would sure seems impressive. But it is nothing compared to other challenges that should be overcome to attain an exceptional life span: an unswerving immune system, not being killed by any domestic accident, human social violence or natural catastrophe, and not suicide yourself over psychological disorders.

I don't understand your first argument. My feeling is that you got side-tracked by the use of the word "engineer" because it shouldn't be used in its literal meaning, but was it the intent of GP?

There are scientific papers, BTW, which engineer solutions by evolutionary algorithms. Is that evolution or engineering? Clearly there's an engineering setup, made of all the constraints you speak about for the evolution process to take place, and that evolution process is also defined artificially, yet just like the real stuff, it follows a set of rules, so where's the divide? Why nature couldn't be engineering life with evolution, but humans could?

Your last point OTOH is quite relevant.

https://www.bbc.com/future/article/20140520-the-girls-who-ne...

> A handful of girls seem to defy one of the biggest certainties in life: ageing. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest. He suspects that the disease is caused by a glitch somewhere in the girls’ DNA. His quest for immortality depends on finding it.

I met a child-like animator, who worked for Disney in Anaheim California (tiny hands). He appeared somewhere around age 9 at his mid 20s, due to a pituitary dysfunction from a car accident.

For a high-profile example, see Andy Milonakis[1]. He is ~40 in this video.

https://www.youtube.com/watch?v=hb9UgsVDwI0

I'm sad this comment hasn't been upvoted higher. The comment explain how the mutation could be possible.

The key is that the mutation would prevent reproduction. If you never age, you never reproduce.

You can think about different cancers. A mutation that causes fatal childhood cancer doesn't get passed on. A mutation that causes prostate cancer can spread.

Aging/death and reproduction seem to be closely related. I suppose maxander would counter that some mutation, given the many people who have lived before, should preserve reproducibility and youthfulness if fractional plasma is able to, but I'd counter that maxander is measuring (or guessing really) the probabilities wrong.

Important caveat for one of the patients mentioned in the article: “Her telomeres were considerably shorter than those of healthy teenagers, suggesting that her cells were ageing at an accelerated rate.“

Aging is weird. Maybe there’s something to be learned from these cases, but it’s very unlikely to be straightforward. Unless you’re a roundworm. We can make those live hundreds of human-relative years. But in those cases it’s a tiny number of genes involved, we have near zero evidence that the same is the case for higher organisms.

There are several kinds of animals with long lifespans https://onekindplanet.org/top-10/top-10-worlds-longest-livin...

Evolution may not select for long life?

https://biology.stackexchange.com/questions/17077/why-does-e...

this is the right answer. once you reach reproduction age and you are able to reproduce, from an evolutionary point of view you're done.

Eh that's too simple in humans. Hanging around longer to tend children and pass on knowledge benefits the survival of your grandchildren, who carry your genes too.

yes. you need to reproduce and to ensure your offsprings reach sexual maturity. but humans are in no way special. we believe we have escaped our biology because of the cultural stratum we posses (ie exchanged memes for genes) but we are still basically animals.

Why couldn't it be true that we want to survive to ensure our grand-offspring and great-grandoffspring reach sexual maturity as well? That's a valid strategy (with tradeoffs, as there are with everything)

we definitely want to survive, even with 0 offsprings. That was not the point. The point was the natural selection does not optimize for the longest surviving humans.

Read the answers in the link I gave -- they give seemingly solid answers (I am no expert).

Not necessarily. Hanging around longer could provide more of a resource drain than the relative benefit, humanity aside, and older people can create limits to societal change that could be a governance beyond material aspects too.

This will sound callous, but some older people really should be allowed to die. There's definitely points of diminishing returns for all involved; I hope that under certain conditions (eg dementia) I'll be allowed to die when I'm decrepit.

Not only that, but you are competing for resources with those in reproductive age. There are some advantages to having older members of he species around (at least in social animals), but only to an extent.

That also means gay people are constantly selected against, yet we have them present for eons.

Let's say someone possessed that mutation. You have to remember prior to 200 years ago, your chances of dying from a disease, an accident, hunger, race, religion would have killed you anyway.

Even today this is true, from different causes. If you eat too many cheeseburgers you die of coronary artery disease before you die of old age. Anybody can still get into a car accident or get cancer. Even minor injuries can result in infection or blood clots. Every meal is another chance to get food poisoning.

Maybe the people who don't age just died of something else eventually.

It has happened, and there are multiple documented cases. At least, the effect has happened — I don’t understand biology well enough to know if any have the cause described in the article.

https://en.m.wikipedia.org/wiki/Brooke_Greenberg

tl;dr: this is not an "age reduction breakthrough", it is both A) a confirmation of what we already knew, which is that parabiosis makes old mice healthier, and B) a finding that virtually proves the mAge clock has nothing useful to say about lifespan

Parabiosis does not substantially extend lifespan (possibly not at all), based on the experiments done so far. Even if it did, it definitely does not double it, which is what would be predicted by naively looking at the halved DNA mAge on the clock.

This paper is very likely intended as another validation of Horvath's mAge clock. The clock shows that there is a strong association between epigenetic state and both chronological age and morbidity risk. Exactly why that is, and what it means, is highly controversial.

Mainstream aging field does not really care about lifespan much anymore. Increasing amount of focus is on so-called "healthspan" - approximately the duration of healthy life, or incidence of morbidity. You would think that you could not affect one without the other, but in fact you can, to a frustrating and surprising degree.

Therefore when you read about "rejuvenation", we are increasingly finding that you can find treatments which improve a broad spectrum of unrelated health markers, that these treatments will affect epigenetic loci predictive of age, and all of this without any substantial effect on lifespan. (From a public policy perspective, this is considered highly desirable, as for public expenditures it would be ideal if people lived perfectly healthy until the moment they keel over, even if we cannot extend the time until they do)

One possibility to keep in mind is that rodents die almost entirely of cancer. So it is possible that some treatment which improves "everything except cancer" would not show any lifespan effect in rodents. This would be one way of reconciling this paper with Horvath's earlier finding that the clock predicts all-cause mortality in humans.

People who had this mutation could have died of causes other than aging.

My first thought too - maybe it's just wishful thinking, but the bible does talk about people who lived for thousands of years. We're prone to dismiss this as hyperbole from uneducated ancients, but maybe they actually did exist and this sort of thing was why.

"Someone slipped up the distinction between years and generations and a legend was born" still seems enormously more probable than anomalous longevity existing but somehow never making it into the wider gene pool.

Do you (they) mean "distinction between years and months"?

That would be between solar cycles and lunar cycles: seems enticing. That would make Methuselah 80yo when he reportedly died; but there are problems still as Seth (for example) became a father at 105, which if it were months would be 8¾ years.

Another possibility is that when it says Methuselah it just means "Methuselah's blood line" or "Methuselah the tribe"; it's a Hebraic thing (elsewhere in the OT) to refer to a tribe as if referring to the founding person.

Or, the person writing down the numbers used a different system, through error or otherwise.

Yeah, they would both account for being off by a factor of 10-20. As would any of a dozen other simple mistakes or embellishments, in all likelihood. IIRC the Skeptic's Annotated Bible has a bunch of direct numerical self-inconsistencies if one needs proof that this sort of slipup is possible, which one shouldn't, because of course it is.

> the bible does talk about people who lived for thousands of years

I don't remember anyone mentioned living for _thousands_ of years. There are plenty of characters that live for hundreds, though. It is believed that Abraham lived to the age of 175, while I believe there was one character that lived into the 300's, but I do not recall their name. It has been a while since I delved into the old testament.

https://en.wikipedia.org/wiki/Methuselah

> Said to have died at the age of 969, he lived the longest of all figures mentioned in the Bible.

that name rings a bell now that I see it. thanks!

edit: Found it on the wikipedia page you linked. I was thinking about Enoch, Methuselah's father, who lived to be 365 years old according to the bible.

Interestingly, Methuselah died the same year that the Flood happened, so you might assume he would have lived longer had his grandson not been instructed to build a party boat that he wasn't invited to...

Nota bene, lunar year vs solar year

I believe in Islam Noah is believed to have lived 950 years. It took him a long time to build the arch.

The other story mentioned in the Quran is about a group of people and their dog who slept in a cave for 309 years and woke up afterwards. I believe they died shortly after. There is an actual chapter in the quran about this called the cave[1].

[1] https://www.clearquran.com/018.html

On a long enough timeline, can't we assume that pretty much everyone is going to die of cancer?

Elephants are massive, and have a very large number of cells compared to humans, yet their rates of cancer aren't higher than ours. Research indicates that it may be due to TP53, a cancer suppression gene that is repeated a ton in the elephant. I could see anti-aging therapy eventually being used in conjunction with gene therapy to strengthen our own tumor suppression capacity.

The body, when it is healthy, generally kills cancerous cells on its own. This is, from what I understand why many cancers come with sickness/age, because your body doesn't react as robustly to broken cells as it did in health and youth. Something like "age reduction" could end up being a cure for many cancers, one could think.

Given that there are cancer's that strike the young as well, I don't know if that would actually work out.

People who are immune to aging are not necessarily immune to a cannonball impacting their face.

If only we could subject enough people to cannonballs we might find one of the super humans I postulate exist.

But train wrecks would allow for significantly higher populations per experiment.

I must ponder this.

They call me Mr...

Well, the obvious explanation to me is that that did happen, and then the person died of some cause unrelated to these specific signalling molecules. Possibly another cause of aging.

In 1850 the leading cause of death in the US census was "zymotic diseases" and cancer caused death in the triple digits. In 2020, almost none of the diseases in the "zymotic" category are significant in the US, but we're still dying. We've cured croup and scarlet fever, so we don't die of those much any more--instead we live long enough to die of heart disease and cancer. Cancer didn't kill many people in 1850, but that's only because "zymotic diseases" killed them before they could develop cancers.[1]

I think it's likely that there are many causes of aging, and they will behave the same way: as we eliminate some causes of aging we'll live long enough to die of other causes of aging that take longer to potentiate.

Given most people who reproduce do so before the age of 50, there's not really an evolutionary pressure to not age--in fact, there may actually be evolutionary pressure to age so you die off and leave more resources for more efficient (younger) organisms carrying your DNA. Ghengis Khan, the most evolutionarily successful person in history, died at 64 or 65. So if a person did produce these signaling molecules, they wouldn't necessarily gain any evolutionary benefit from them.

[1] Obviously "zymotic diseases" is a nonsense category in modern medicine--most were bacterial infections, some other forms of infections, some completely misattributed to infection. The point here is that most of them weren't cancers or heart disease--the things that kill Americans today.

There are tons of reasons this wouldn’t have happened. Lots of this is speculation but:

Seems likely this is a gradient, not a binary thing, so perhaps someone with a beneficial mutation would just live a little longer. There’s not a ton of evolutionary pressure at the old age side of the spectrum, you’re not reproducing a lot, so it may not get picked up.

Wilder speculation: it could be that indeed this has been happening and is why humans live about 2x as long as chimps and gorillas.

Personally I think it’s quite unlikely that in humans single genes would have large deltas on age. There are maybe a few hints from supercentenarians (https://en.wikipedia.org/wiki/Research_into_centenarians) that telomerase and other genes have some effect, but the “one gene for aging” in humans is elusive. As a result, it’s hard to predict how all this would play out evolutionarily.

I would be very careful about trusting research on supercentenarians. There is a substantial amount of evidence (https://statmodeling.stat.columbia.edu/2019/08/06/are-superc...) that a significant number of "supercentenarians" are simply pension/tax frauds taking up the names of dead people to keep collecting pensions.

Entirely possible! Hadn’t heard that critique but makes sense and something to control for.

Yup, your "hot take" is the core of "Lifespan" by Dr. David Sinclair.

To put it simply, a population with aging is more fit than a population without. The speed at which beneficial mutations in a population reach saturation in the gene pool is a function of the number of generations that have gone by. So we can expect some downward selective pressure on lifespan.

So then, once a population reaches "ideal" mutations, if that is possible, then wouldn't the opposite start happening?

There is no static ideal. The total environment is incessantly changing, and organisms are constantly adapting.

I'm not an evolutionary biologist, but why wouldn't the selection pressure be related to the speed at which offspring are produced, and not the age of the parent? And why wouldn't a parent that lives a long time and thus produces more offspring be evolutionarily fit?

There are a lot of factors involved in having viable offspring. For example, you need enough resources to sufficiently feed and nurture the children you already have. So having more offspring than some ideal amount for the environment can be detrimental. But parents also compete with their offspring for resources. Aging and dying is eventually the best thing a parent can do for their children.

This doesn't really work at the individual level. Parents compete with their children, but so does everybody else. Having two parents competing with you for resources in addition to the other ten thousand people in your local community is not a meaningful difference.

Meanwhile if there was an entire community like this then the people living longer still wouldn't be at a disadvantage, the community would just have a different equilibrium. The surviving communities could e.g. have fewer children on average (you only have to replace people who die in accidents) or would expand their territory over time (expanding population can control more territory).

That's a fair point about competing with the community. I was thinking of "parents" in aggregate, so the previous generation vs the next, but I didn't word it right.

But if everyone lived longer than required, i.e. the minimum ideal for raising viable offspring, then this population stood to be out-competed by another population that aged at a more efficient rate. Individuals in a population aging at an optimal rate is an evolutionary advantage to the population.

This might explain why genes for aging exist but doesn't really explain why genes for not aging don't exist. You could have a stable community where e.g. 15% of the population doesn't age and not run into community-level problems because they aren't that large of a percentage of the community, so where are they?

Hard to say. At least in the case of humans, high generational turnover might have been beneficial in our evolution from aquatic apes or whatever our ancestors were to modern humans. And so longevity genes were selected against. It might be the case that most species' environments are too dynamic for super longevity genes to be beneficial rather than faster population adaptation.

The older you get the more difficult it is to conceive children as well as raise them. Given that most people have a partner that is roughly the same age as them, and that there would be a much smaller percentage chance of pairing with someone with the same long life trait, the period of time that they are likely to have children probably stays consistent with societal norms. Therefore living a long life wouldn't increase the number of offspring and wouldn't provide any evnolutionary benefit.

> The older you get the more difficult it is to conceive children as well as raise them.

Are you trying to provide an evolutionary justification for aging by using aging itself as a reason?

At that point you are getting into some of the same reward dynamics that you see with honesty in intra-species signaling. Particularly that an organism in a population may wish to signal honestly even if it knows it is unfit so that the overall population health can improve. From what I recall, many evolutionary biologists disliked the hypothesis, instead preferring the costly signaling theory as an explanation of why signals remain honest.

https://en.wikipedia.org/wiki/Signalling_theory

That assumes that the species is not smarter than nature at assessing what is "more fit" for them. For example, smart chicken that wanted to go to alpha centauri might engineer themselves to live much longer in a way that nature never would.

Until recently, I assume even a human with an anti-aging mutation would've been killed by something else within a typical lifespan. War, disease, lung damage from wood burning stoves or coal, injuries while working, and so on.

Also, if it takes 4 different mutations (assuming each of 4 injections is a different substance), it might be very unlikely for all 4 to happen in one individual, and any 1 mutation may not give that individual any particular reproductive advantage.

Death and aging is a feature of evolution. These features evolved to further enable evolution and allow it to iterate more quickly. Species that iterated more quickly, and therefore evolved more quickly were more successful. Features that are deliberately evolved exist within many different genes as a mechanism to protect the feature, this is why dropout works so well on neural networks.

I wouldn't say a feature of evolution. Perhaps it is an adaptation of sexually reproducing multicellular life but it certainly doesn't apply to all life.

Just like organisms evolve things such as vision, frontal lobes, etc, we have evolved aging because it ultimately positively impacts the survival of species. This makes it an evolved feature, wouldn't you say?

Are there any good articles or books that make this case in a form that's not a just so story? You're just kind of stipulating that it's beneficial.

I think it's more likely that, as many others in this thread have observed, longevity is ignored while evolution optimizes for other things, which I would distinguish from something that specifically evolved like vision. Things can die perfectly well on their own without dying needing to be optimized. It would also be more plausible to me that death was evolved if it had some clear, functional, deliberate mechanism by which it was enacted, the way that eyes or lungs are clearly purposeful and functional. Death happens as an interference with function rather than as someone handled by an organ or internal system.

The quantity of a particular species in an ecosystem has an equilibrium point. The optimal amount of a particular species is a number. If there's no death, this number will be pushed out of equilibrium, and the given species isn't dedicating its niche in the ecosystem to the most superior 'version' of itself, therefore not investing the niche resources in the best bet of progressing the species.

This is more than speculation, how is this not beneficial?

Most death in those systems is due to predation though. Just look at what happens when natural predators are removed, the population explodes and then busts due to starvation. If your conjecture was correct then the population would self-regulate by aging and dieing before reaching that point.

It would simply take too many genetic changes in a too short period of time to change the aging rate to compensate for such a sudden change in the environment. Remember, genetic adaptation can take years, decades, or even centuries (think lactose intolerance which happens to be 1 gene).

Evolution only cares about whether you have viable offspring. Beyond that longevity could be a harmful feature because the long-lived would be competing with the fertile individuals for resources.

It all boils down to "is living longer an evolutionary advantage ?"

While the article mentions the current paradigm (accumulated DNA damage as the prevailing view of why our cells slow down), it doesn't address how it is wrong. In which case, cells with the right signals will behave more actively, but this could also lead to faster onset of cancer.

A more interesting approach to me seems almost feasible with current technology, assuming CRISPR will soon be able to replace DNA without causing more side effect DNA damage than it fixes.

Take a healthy human blastocyst, derived from healthy young relatives of the patient (likely to have compatible mitochondrial DNA). Now, determine the patient's original DNA structure. This would occur by sampling various cell lineages and using a statistical model to estimate the original DNA of the patient as a baby. Now, take some stem cells from the blastocyst and replace the DNA with the patient's DNA. Generate a culture of different stem cells and inject them throughout the patient's body. The patient now has cell lineages with fresh telomeres that will be actively dividing for another 6 decades. Perhaps additional signaling regulation would be necessary to prevent types of growth that would be unwanted in adults.

Any experts want to poke holes at this idea? I have no formal training in biotech but I always thought this seemed like the cure to non-structural age related diseases. The harder part seems like cleaning and regrowing new veins and arteries, and brain repair.

> how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment?

FWIW, I'm pretty skeptical of this announcement, but (assuming it's correct), it's possible that you need multiple signalling factors to achieve the age-reduction and that one single mutation might not do the trick.

Let's say that you needed four precise mutations to achieve the age reduction, then the probability of getting all of them in a single individual would be quite low.

But like I said, this announcement has a bad smell to me. In particular, the fact that they are not revealing the "rejuvenating factors" as well as the fact that they have not demonstrated age prolongation.

Finally, the complaint about the aging field being focused on cellular damage feels a little "straw-man-y" to me. I'm certainly not an expert in the field, but I imagine there are numerous researchers hunting for age-related signalling molecules.

It would have to confer benefits before reproductive age in order to be a trait for which there's evolutionary pressure (to first order). Something that makes you more likely to live an extra decade almost certainly won't make you have more kids or make your kids more likely to survive, so there's no selection pressure for those genes.

> how is it that none of them have possessed a mutation which (...) endogenously produced the signalling molecules which Katcher is proposing as treatment?

Because evolution is a random-driven process. (in the same way that we carry a number of traits that made our survival harder)

> of the billions of humans that have existed, how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment?

How would we know? What fraction of people in the past actually dies from old age and complications of old age, and not disease, infection, or strife such as wars or other conflict?

In the past, I imagine not degrading due to age would be at best an extra few decades of time until you got a bad flu, or pneumonia, or an infection, or were killed on a battlefield, or if you were female, died from complications of giving birth.

We don’t know it’s zero. What fraction of humans who have ever lived have died of old age?

We could have age-proof people living among us today who happen to die in car accidents or any number of other causes.

Seems like having this mutation from the beginning might be very different from getting it when you're 20+. Would you simply fail to develop even to viable infant stage?

Because, immortal creatures are counter-adaptive. They become a load on their population as they accumulate injuries and disease damage, until they are an ancient hulking parasite on their line?

Maybe because people tend to reproduce fairly early in life (usually half of lifespan) so living an extra X years doesn't really allow you to have more children, and therefore the mutation of longer life doesn't get a huge enough advantage in natural selection?

Right. And I suppose that the other side of the same coin is that we might want to deliberately delay having children as long as possible if we were actually trying to steer evolution toward optimising for longevity.

Not aging doesn’t mean not mortal. Until very recently, old age did not make it high on the top causes of death. Not aging doesn’t really help against hunger, illness, and accidents

Living a long time could be advantageous for the individual but disadvantageous for the society.

Evolution happens at all scales, not just the creature scale.

"The man from the earth" movie comes to mind reading this. Should have ctrl+f 'ed before commenting. It's a great movie.

So you can live longer, but what about cancer?

Maybe living longer means you don't get cancer. There are animals with extremely low or even zero rates of cancer.

Some people could have had that molecule, but it might have been undesirable for long-term survival of their tribe.

Reply on news.ycombinator.com