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That's actually interesting.

You have to wonder what low-hanging fruit is coming up by combining mass sequencing with medical (and other) history.

I wonder whether some group will start some gene therapy based on this research.
I’d love this to be incorporated into 23andme and the like. Would change one’s approach to retirement and savings if you knew how long you needed money for…
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As someone 99% confident that we're on the verge of discovering a way of reversing aging, it makes me incredibly sad, almost angry, to realize that many people are literally planning how they'll die.
If we can reverse ageing, your entire life will be spent planning how to avoid existential risks. When you can live forever even crossing the road becomes too risky.
Not necessarily, because people do plenty of risky activities today which shorten their life expectancies.
Is that new? Humans have always planned how they die, and how it will affect those around them. Isn't that the point of a will, for instance?
Idk, I just don't understand the meaning of a life that has an end, and thus "leaving something behind" makes no sense to me. Why leave something behind if the moment a person dies the entire universe ceases to exist for them?
There are things worse than dying, similarly, there are things that are better than what can be experienced
It makes sense if you believe other people exist in a meaningful way similar to your own conscious existence. When you die, the universe doesn't cease to exist for them. So you are not leaving things behind for your own benefit. It's for other people.

Conversely, if you believe the universe ceases to exist entirely when you die, you believe other people cease to exist too. In this case, perhaps the only consistent way to think of other people is that they are not like you when you are alive either.

From a more down to Earth perspective, if I left the planet on a one-way interstellar FTL journey, confident I would never return and that there was no way to communicate with the people I left behind, even though it would be a relief in some ways and I'd stop caring about people left behind, I'd still want to arrange good things for some of them after my departure. Because I'm nice like that.

> From a more down to Earth perspective, if I left the planet on a one-way interstellar FTL journey, confident I would never return and that there was no way to communicate with the people I left behind, even though it would be a relief in some ways and I'd stop caring about people left behind, I'd still want to arrange good things for some of them after my departure. Because I'm nice like that.

Well, you can't be so sure you'll never see them again and you'll never be able to communicate with them, because of scientific advances and such. The only truly irreversible thing that could happen to a human being is death itself. Everything else being reversible (or eventually reversible) is the nice part about being alive.

Well, the universe doesn’t need me to keep on going, and it makes me happy while I’m alive that I can help my fellow humans out.

That doesn’t really work out in a logical sense if you assume that people are purely self interested, but they aren’t, their behavior is optimized by evolution and self interest is only one of many complicated feelings that people have.

I still share your optimism though that we might cure the diseases of aging, so that people do not suffer from slow decline.

May I ask why you are so confident? Sounds very sci-fi, though I’d love for it to be true.
Do you have sources or reading material to substantiate your confidence? I'm interested in this area.
1. https://old.reddit.com/r/longevity/

2. https://joshmitteldorf.scienceblog.com (be sure to follow the links to research papers and read the comments)

3. I also made a playlist with videos and lectures on the topic: https://www.youtube.com/playlist?list=PLLvA7pB41pDk27XOjqbXi...

Imagine the misfortune of being 80 years old when humanity finally figured out how to do this.
I think the worst would be discovering that we can cure old age but only in utero, thus the next generation will be the immoral ones but we will all die eventually.
The worst would be discovering we can cure old age, but only for people rich enough to pay for the extraordinarily expensive treatment...
No, imagine the fortune because you'll now have your body reverted to a younger age.
Touche.

If it's possible do you know why evolution didn't figure out how to do this? Seems like it would be a good adaptation

This one is easy. First of all, evolution only cares about the species as a whole, so the survival of an individual, especially after they've produced their offspring, doesn't matter much. Second, in the wild, animals will be killed by predators much more quickly than they'd die of old age, so all the mutations that only manifest negatively in older age have never had a chance to be selected against.

Besides, the whole premise of evolution is that older generations die.

(disclaimer: I'm a software developer, not a biologist, but I'm fascinated by biology)

You got it in reverse: evolution only "cares" about the individual

https://en.wikipedia.org/wiki/The_Red_Queen:_Sex_and_the_Evo...

Lol. I usually read HN to follow tech trends. This thread in hilariously uninformed. It is as shaky as me writing a critique of database engines would be.

On this specific subthread: yes the individual is the level of selection (mainly) but Dawkins has renewed interest in the sequence variant as the ultimate unit of selection. We are protoplasmic bags of gene variants, some of which make it to the next generations.

Evolution optimizes for reproduction, not long life. Long life is likely not very beneficial to reproduction and a large population of older members is a drain on resources. At least, it was until we got to the Information Age.
Sometimes long life is key to reproduction, for example old turtles are bigger and safer from predators (before humans came) and have more offsprings than younger ones (yearly and in total). Turtles can grow very old because there is reproduction advantage to that.
I'm sorry but this is extremely weak none of this brings it anywhere close to 99%. This is youtube, a blog and reddit. Seriously.
So? There are links to real research papers written by real scientists.
Why do you think we can cure aging when we haven’t solved or even made any progress tackling much simpler problems like Alzheimer’s?
They are not "much simpler" — they're direct consequences of aging. It's like trying to put a fresh coat of paint on a car that has almost rusted through. It makes more sense to address the root cause than its many consequences.
Grishka needs to read more widely on this topic. Start with Caleb E. Finch’s magisterial book “Longevity, Senescence, and the Genome” (University of Chicago Press, 1990). Or read my review with Michael Hook: “Genetic Cartography of Longevity in Humans and Mice: Current Landscape and Horizons”.

Just do a text string search. It is on PubMed Central and free.

For a counterpoint to the confidence, but still a very high-confidence prediction, Aubrey de Grey has recently estimated a 50% chance that we'll hit longevity escape velocity by 2036. That is, enough treatments will be available to people such that they can expect their lifespans to be Y, an increase from their previous X. But before they hit Y age, there'll be new treatments developed they can take that extend expected life age even further to Z, and so on, until we arrive at general treatments that extend life indefinitely.

Aubrey is the foremost expert in the whole field of longevity research as far as I'm concerned, so I don't have any reason to be more or less confident than him about any aspect of it. If you haven't read it, his Ending Aging book covers a lot of details. It was published in 2007 but has still held up, especially with overall strategy. Apart from the various medical developments since then, another encouraging sign is the increase in newly formed companies in the space, lowering the need for philanthropy/government grants. https://agingbiotech.info/ has a list

What makes you so sure? Personally, that bubble burst for me a long time ago. I hope I'm wrong. I'd love a new insight or even any tips that might give me more of a chance to see that discovery.
We are going to die and never come back, 100%.
The societal ramifications of a large number of people living past 100 would be unprecedented.
They certainly will be, but not necessarily for the worse. Imagine oil billionaires having to live through the consequences of their actions. Imagine the societal benefits of people being able to use their decades of valuable experience for much longer, rather than having it die with them.

I do believe it’s going to happen, but personally I’m more pessimistic than GP and don’t think it’ll be within my lifetime. Medical research is so tightly regulated when it comes to testing on humans (for good reason!), and there isn’t enough money going into the field.

> Imagine oil billionaires having to live through the consequences of their actions.

They won’t be. They’ll be billionaires, able to buy any scarce resource they need to continue their lifestyle. They might need to cut back on their monthly yacht purchase, maybe, but little else.

That's one way to look at it.

Another is that this is the endgame for medicine as there is no other path forward. A huge amount of resources, both human and monetary, is spent to care for elderly people to slow the decline of their fragile health as much as possible — while still inevitably failing eventually. It's as if we've almost hit the ceiling of what can be done here with "traditional" methods. So it's the next logical step to declare aging itself a disease, because it's ultimately the cause of all those conditions, and start looking for the ways to reverse and/or prevent it.

I can say that about dozens of technologies that already exist, and several others besides a mere 18 year boost to average life expectancy that are actively being worked on.
Even if we discover the secret to everlasting life there are going to be plenty of people who would like to die eventually. Also if I’m 90 and in poor health the idea of living forever doesn’t sound very appealing in general.

I think your premise is incredibly ambitious but even if it’s true the vast majority of people aren’t going to get access to the veritable fountain of youth anyways, at least not for a very long time because society will have to fundamentally change both to accommodate the idea and also to allow your average person to have the means to obtain it.

If you are 90 and in poor health, it's likely because you are dying albeit slowly. The technology for everlasting life will likely reverse or halt the breakdown of basic bodily functions due to 'old age' and may rejuvenate organs who are simply suffering from maintenance issues.

So in the end, a cure for death is also a cure for myriad amount of ailments.

Maybe. This is speculation on speculation.

It certainly makes a lot more sense for people to plan their lives around our current understanding of mortality than an increasingly hard to believe pyramid of hypotheticals as the GP has contended.

The speculation is very convincing, it goes like this: 1) Senescence is a collection of symptoms caused by incomplete repair mechanisms allowing damage to build up, 2) some level of damage has very little ill effects (e.g. the amount you've collected on your 25th birthday), and 3) there are interventions that stop the accumulation of damage or even reverse it.

I believe currently only 3) is a bit controversial, but since there are biologically immortal organisms I find it plausible that it's possible.

> So in the end, a cure for death is also a cure for myriad amount of ailments.

Not if you're an amputee. There's a certain amount of damage to the body that isn't due to just aging.

Google Michael Levin or watch his lectures here: https://www.youtube.com/playlist?list=PLLvA7pB41pDk27XOjqbXi...

We'll probably figure out how to regrow limbs and organs soon.

Full Self Driving soon?
Lol. It should be easy to make a self-driving car that would coordinate its actions with surrounding self-driving vehicles. It's extremely hard to make it behave well in an environment where some of the cars are driven by humans.

So, no, not soon. Unless we introduce dedicated lanes where only self-driving cars are allowed.

When is the singularity going to happen?
2012. We're all machine elves now.
That's just egocide. We've had plants that do that for millennia.
The current best treatment for death is to contribute to social health and knowledge. Transmit both to your progeny and younger colleagues. Your particular atoms and molecules are really not all the unique and wonderful.
Your atoms and molecules might not matter, and indeed get replaced many times as a normal process throughout your life, but your consciousness is wonderful and valuable.
and also to allow your average person to have the means to obtain it

It's basically the opposite. Health care for old people is very expensive, precisely because they're old. Reversing or preventing aging to the point where everyone has the health profile of a 30 year old would save a fortune.

I won't contend the point you're making regarding the costs of healthcare for population that is healthier on average vs one that isn't (elderly). That's true.

The idea that our collective human society is going to be handing out everlasting life to anyone who wants it is, even in light of this, something I can't begin to fathom. Perhaps if the arrival of the immortality drug also coincides with the arrival of a utopian society that actually cares about people beyond their basic (and incredibly power-imbalanced) economics that are skewed to benefit corporations not only over people, but over governments, then I can accept it.

But in context of the way the world currently works, this is an incredibly optimistic or naïve assertation to me. People die every day even in the most developed nations due to a lack of access to healthcare, food and/or shelter.

If you had to bet, what would you say is the percentage of people that are currently planning how to die but are doing so in vain?
How foolish. May you live forever is how I would curse my worst enemies.
So how do I become your enemy? :D
Coud we be platonic enemies, please?
How is it logical to know living forever is bad when you there isn't a single person on the face of the earth who has done so? This is not a rational statement or philosophy. It is simply speculation as we have no evidence whether this is good or bad unless we talk to someone who has experienced it. Fundamentally speaking... no one has experienced this so we have no evidence FOR or against it.

Additionally "living forever" isn't invulnerable immortality where you are doomed to float around alive in the solar system long after the sun has inflated and pulverized the earth as a red giant... You'll still die well before that.

You can also always choose when to kill yourself, whenever. Logically any form of "living forever" described as a scientific possibility is actually more of a "you can choose when you die" or a "you can live much longer than normal"

If you are asking to live as long as you desire, I am all for that! But the comment I was replying to was ridiculing the idea of planning for the eventual end of one's existence so presumably they want to live literally forever. And that's a very long time.

For arguments sake imagine that your consciousness is transferred into a simulation that runs at a highly accelerated rate so you can experience a very long existence. The custodian of the simulation is benevolent, it tries to keep you happy, lets you shape the world in whatever way you want but the one hard rule is that you are not allowed to end.

You will probably have an awesome time for the first few hundred years. So many fun experiences you could only dream of before. You can explore the stars, turn the world into paradise, come up with new forms of art that no one has imagined.

After a few thousand years things might start getting a bit samey but you will still find new things to do. But how about after a few million years? Or billion? It might start getting pretty boring. You have done all the fun things countless times and all the terrible things too just to do something different. But your looooong adventure is only beginning! There is no exit button. Welcome to hell.

The scenario is not completely implausible, agreed? I think one of the Iain M Banks novels had something similar going on. I think the custodian there was evil but I am arguing that on the looong run that makes little difference.

One might argue that they would transform themselves into something that can tolerate the infinite existence but I call that cheating, such a thing wouldn't really be you anymore. And the custodian might see it that way too.

Pretty much no one who advocates for effective biological immortality also argues that you should be forced to live forever against your will. So while it can be fun to speculate on such, as it can be fun to look at torture methods (the video game Amnesia has a good section on this), it shouldn't be mistaken for people advocating for such.

The ridicule the comment made is for a mindset that actually happens right now, talk to some retired boomer relatives. A lot of them have had actuarial consultations and some of those are treating it almost like gospel, like the other comment wishing he could do the same given 23andMe reporting. This leads to them depleting their savings (mostly held up in "safe" investments that aren't expected to grow or shrink much over the relevant timespan) at some rate so that it gets close to $0 by the time they can expect to die. Some older people have already made it long enough to go past that point, and they get into the same situations that retirees without any savings get into. i.e. you hear about old ladies subsisting on dog food because their only source of income is a small social security check.

A better mindset is the one used by the FIRE crowd, which applies just as well if you're "retired" at 30 or 60: recognize index funds are not just pretty safe but also give a pretty high confidence minimal rate of return, plan for average x% returns per year, and don't withdraw more than x% for income, so that your savings never decreases but in fact increases. This way you can retire whenever your savings hits the right number to support your required income indefinitely, rather than retiring when your savings hits the right number to provide income only for the next X years until you die.

(I shouldn't have to say it but will: this is a theoretical optimal modeling strategy, reality will be messier, any real plan should analyze possible setbacks and ways to deal with them -- the easiest way typically being to seek work again for some period of time, which tends to be easier the more biologically young you are. And of course, regardless of biological immortality or whatever, you could be an unlucky passenger in a car driving down the freeway when a random brick from a truck in the oncoming lane comes loose and collides with your head.)

First off nobody realistically talks about this. It's speculation. The topic at hand is talking about endeavors in the realm of reality. Not even mountains can last billions and billions of years, nobody is talking about immortality at that scale simply because it won't ever happen.

So if we're speculating here your argument is that boredom is a curse. At my age I'm already bored every single day of my life.

I'd rather be bored than be dead. But again this is speculation. I'd rather be bored for 50 years than die at 50 but would I be the same at 5 billion? Truthfully nobody knows. Even 50 Years is a long time to be bored but if you're not bored at 50 what makes you suddenly conclude that 5 billion is too much?

There's no evidence or weight behind this philosophy. Boredom does not equate to being cursed.

Yep, there also won't ever be a person who lives forever, since one can only observe someone who has lived for a finite amount of time.

But whether it's good or bad is something that only an individual can determine. It's more/less along the same lines as the question "is life worth living?"

Agreed? Why are people so afraid of death? If you're religious, then you wouldn't want to live forever. If you think you just disappear into the void when you die, then it doesn't matter when you die (which you will eventually).
Who says they're afraid? Maybe some people just enjoy life.
I don’t know why people refuse to admit it. I’m afraid to die. Not of the process, but of not existing.

So is pretty much every other creature. We all try to avoid death.

If you decide you don't like it, take up wingsuit jumping. You'll likely die before that long and enjoy your remaining time, so win-win.
A few counter thoughts:

* I love peppermint ice cream, but I'd probably get tired of it after a million gallons.

* I'm looking forward to retirement in a few years. I don't desire to work for 5000 years.

* A thing in infinite supply has little value. Why would another year of life be any different?

* Marriages would become limited term contracts, and partners would change every few decades

* Unless society figures out a way to address poverty, do you think the billions of impoverished people will want to live forever?

* Having children will be limited to a chosen few, probably the wealthiest.

* Suicide will have to become socially acceptable when people become

Honestly, I think even if the technology is developed, it will be available only to the rich and powerful. They would be willing to prevent the technology from becoming widely available because it would upset the current order and they dare not risk losing their position of privilege.

It's nice to have an option to not age and die, anyway. We have no idea what the world will be like in a decade, let alone 5000 years.

> I love peppermint ice cream, but I'd probably get tired of it after a million gallons.

So you'll take a break. Then you'll crave some more. The problem with suicide is that one can't change their mind, because there's no mind any more.

> A thing in infinite supply has little value. Why would another year of life be any different?

We have effectively unlimited supply of water, yet it has a lot of value to us because a person can't survive without water.

* People don't like changing their minds once they find something that works so we'll have huge chunks of people with moral compasses from hundreds of years ago
* I love peppermint ice cream, but I'd probably get tired of it after a million gallons. - Who will eat the same food all the time?

* I'm looking forward to retirement in a few years. I don't desire to work for 5000 years. -You will encounter a means to not need to "work"

* A thing in infinite supply has little value. Why would another year of life be any different? - Statistically you will die of a horrible accident earlier... don worry

* Marriages would become limited term contracts, and partners would change every few decades - YES !

* Unless society figures out a way to address poverty, do you think the billions of impoverished people will want to live forever? - with free information everywhere... Who will not get a chance to get a great education on his first 200 years?

* Having children will be limited to a chosen few, probably the wealthiest. - ???????

* Suicide will have to become socially acceptable when people become - Again... - Statistically you will die of a horrible accident earlier... don worry

I like to imagine that this is what cells think right before they become cancerous.
> we're on the verge of discovering a way of reversing aging

This happens shortly after Tesla makes the million full self driving robotaxis at the end of 2020?

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We would all be wise to plan along these lines until your 99% sure-thing is proved. I study the genetics of longevity and alas I am gracefully planning to die.
My guess is that everlasting life will just open the door to other problems we didn't consider.

Fix one bug, say hello to another.

We'll fix them as we encounter them. At some point the human body will be completely reverse engineered anyway.
Yeah the next issue will be obvious and have an easy solution. And the distinction between fixing a bug and breaking a feature will always be clear :) /s
There are many different forms of aging. Which one are we on the verge of reversing and how?
As someone who is literally the only surviving member of my childhood block's clique of 80s boys, I laugh loudly in your general direction.
I'm a strong supporter of this sort of research but our lack of fundamental understanding of most life processes does not inspire confidence we'll crack this puzzle soon.

More likely, through use of bioinformatics to customize chronic disease treatments, we'll get another few decades of average life expectancy over the next century.

Why would knowing you are great at DNA repair guard against other things befalling and endangering the elderly, and very mundane, like falling and breaking a bone, increasingly hard to heal the older one is, and thus at times a gateway to further injury cascade?
There are many ways one can die or be injured. But knowing the likely upper limit of your longevity can change how you approach finances and risk.
I find it good to remember that genes are like re-used variables that do 100s of things in a giant 1mil lines of code file.

Just cuz they identified one gene doesn't mean that it doesn't require other activations as well. Or that expressing that one gene will have that much of an effect.

So sure, you could have an idea of the upper limit but definitely not the whole story.

Circulating levels of GH/Insulin/IGF and other hormone like chemicals also play a huge factor in longevity as well.

https://pubmed.ncbi.nlm.nih.gov/22396862/

So far, I suspect such genetic analysis has too much uncertainty to use as individual guidance.

Knowing that an average person has say an 85% chance to exceed age 70, but you only have a 68% chance, would you dramatically change your life choices?

In this case it’s not about that, but rather if you possess what it takes to hit 100+.
I look at my dad, and grandfathers deaths, and pray. As to retirement---I just hope jobs that are easy on the body, and don't require much thought are still around in a few years.

I figure the only thing that might give me a few more years them is I wasen't a huge smoker.

Although, they all had easier financial lives than myself which puts me in the early death catagory?

No one makes it out alive
Without knowing your entire genome (23andme looks at markers and not much else) it's going to be hard to give an accurate answer to that sort of question. And that's aside from non-genetic risks of death that the other commenters have already pointed out.
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Yes, and genomes only a small but significant part of the longevity puzzle.
Indeed, hence the nature vs nurture debate. The environment and how it indirectly interacts with the genome is just as big of a factor.
> I’d love this to be incorporated into 23andme and the like.

Watch out - your insurance company would probably love that too, if they can get their hands on the data.

I mean, it would help my government better plan health care resources and where they're needed. "Ok, this region over here is going to have a lot of cancers, build a treatment clinic there".
You mean like everything governments know about smoking, drug use disorders, poor diet, exposure to environmental toxicants, and how they have used that information with marvelous efficiency? Yep.
I used to get those reports when 23andme started. They are not allowed to give them for 10+ years now. I m not in the US - we have universal healthcare. Disallowing me to have those reports is almost violating my rights
I’m not sure if it’s still an option but when 23andme first started getting looked at by regulators and shut off the health reporting they allowed you to download all of your raw data. I wish I could remember the name of it but there was a GitHub repo (I think written in Python?) that you could run against your raw data and it would spit out the health results that 23andme withheld.
Yes i have those (from 10+ years ago) and there is also promethease. But the ban still makes negative sense
No, they will be smart enough to know this is bogus.
I have not read the original paper yet, but I can tell you that longevity is not controlled by any one process. Its complicated. Simple stories are simply wrong. That complexity is amplified by environmental factors and intense gene-by-environmental non-linearities. We have to live with this reality until we die ;-)
> Would change one’s approach to retirement and savings if you knew how long you needed money for…

Popular wisdom amongst early retirement groups is you need 25x your annual spending to retire indefinitely. This figure is based on average stock market returns, so as long as you take out less than you earn each year you are golden. Some years it won't do so well, others it'll do better, but overall you should be safe.

https://www.madfientist.com/safe-withdrawal-rate/

Yes, but that is based on not knowing how long you'll live, which means you can't risk eating much into your capital.

But if you somehow could know exactly how long you'll live, it could be adjusted accordingly, and especially as you get closer.

E.g. to take an extreme example: If you know you only have 10 years left, then obviously you could just keep your money as cash to avoid market risks, and spend 10% each of your remaining years.

Even if it's not 100% certain, if you were able to get a very precise estimate, there'd be room for a lot better annuity rates on offer for people with a shorter life expectancy.

We should treat this study and the discussion of the relevance of the results as being highly speculative.

Firstly, near all genetic variants that have been found to correlate with age in one study population fail to replicate in other study populations, and this is true of studies with cohorts consisting of thousands of individuals. The study here used a primary cohort of less than 100 individuals over the age of 100. This is ever the challenge in research focused on extreme old age: very few people make it that far. There was a secondary validation cohort of a few hundred centenarians, but I'm not sure that should increase our confidence in the data, given the existence of other studies that did much the same thing and still failed to replicate.

Secondly, given the identification of a genetic variant, near everything one can say about it is quite speculative in advance of much more detailed research into how exactly that variant changes cell behavior.

Lastly, the most robust data established to date on the contributions of genetic variants to human longevity, with studies pulling from very large national databases such as the UK Biobank, suggests that genetics has only a minor role to play. Lifestyle choices and exposure to pathogens are the dominant factors. In the case of long-lived families, cultural transmission of lifestyle choices relating to longevity seems a more plausible explanation than genetics, given the rest of the literature as it presently stands.

Bingo. Not sure why every biology/medicine post on HN is unquestioningly upvoted and accepted as established fact by so many commenters, who always discuss the applications instead of the validity. I wish this community of all would know better.
Are the SNP's of this known?
From what I can see the analysis was not highly significant for the individual SNPs (p>0.1) but they combined it into a gene based analysis that brought the significance up. I'm not enough of a statistician to know how valid that procedure is but I would say even if you find out the individual SNPs it probably isn't too reliable to interpret them on their own.
Somewhat related to this, elephants have around 20 copies of TP53, the master ‘protector of the genome’ gene that senses DNA damage and reacts to it. With lots of cells you need lots of protection against cancer. I wonder if blue whales have more. Response to somatic mutation is the name of the game for organisms with very old or very many cells.
Some human cells, notably within the immune system must mutate to function. If they do not mutate, you will die as bacteria and viruses mutate faster than your defences can adapt.
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This sounds interesting, do you have any references for further reading?
https://en.wikipedia.org/wiki/Somatic_hypermutation

Treatments that reduce mutations in general could make the immune system less effective (increasing your chances of dying of disease, and that of passing a disease on to others). It could also cause fewer mutations in your offspring, which might hurt human evolution over many hundreds of generations.

Curing cancer tomorrow, but with side effects of dramatically increasing transmission and deaths by transmissible disease, and causing humans to die out from failure to adapt to future environments seems like overall a bad plan. It's certainly something we'll need to fully understand before making use of.

Not right. Get some hard core background in population genetics. If you want a great (but costly) text on this topic with real insight—, then read Lynch’s The Origins of Genome Architecture.
What's so good about it and how dated is it? The book is 13 years old, a lot is happening in that field no?
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Nope: there is a huge difference between MHC gene recombination and mutation.
Also these 100+ year old people hit multiple genetic jackpots, avoiding diseases of suboptimal metabolism and cellular senescence as well. There are many other populations that could be analyzed: the 70+ year old relentless sunbathers with leathery skin but no skin cancers, the 90 year olds smoking 2 packs a day for 60 years with pristine lungs. Because these people don’t end up in clinics there is not necessarily as much known about their innate resilience to carcinogens or other malign influences.
Even 100+ year old people tend to end up in healthcare settings for a short while before they die.
Could it be that they then don't get as thoroughly investigated, as someone else who is, say, 50 or 75 and also ends up in the hospital? The 100+ won't live that much longer anyway
Are there really people who have smoked two packs a day for 60 years with pristine lungs?
I think the poster may have meant cancer free. I don't think its probable that a smoker wouldn't have some sort of buildup or other impairment
No. Emphysema is pretty much a given for lifelong smokers who continue smoking past their 45th birthday.
You should have met my granda who in India smoked more than a pack a day all his life and died in his 80s while he did more manual labour each day on his farms everyday than I workout in my 20s.
Similar story here. It's understandable that someone may be skeptic, but it still needs to be shared.
My great-grandfather smoked every day, starting at age 9. He died of heart failure at 96.
Do you have a reference? It would be hard to establish causality. Genetic drift extremely important in megafauna due to very small population size. Selection has to be exceedingly strong. Read Mike Lynch’s lovely paper in PNAS in 2007 (free from PubMed)—The frailty of adaptive hypotheses for the origin of organismal complexity. There is a high risk of “just so” stories to “explain” biological processes and phenomena. Nassim Taleb’s Black Swan well worth reading; Chapter 6 in particular.
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Cancer becomes almost irrelevant as you get really old: https://flowingdata.com/2016/01/05/causes-of-death/

Not to say that the other reasons for death are not related to mutations. Edit: also I worry I am making a selection bias - presumably extra protection from cancer may be required along with many other traits to become a centenarian (A and B and C …).

It becomes almost irrelevant as you get really old, but that is not because cancer goes away but because cancer has already killed a good chunk of those most susceptible and other causes becomes more likely to kill the remainder before cancer gets a chance.
> but because cancer has already killed a good chunk of those most susceptible

Why do you think that?

Death rates for cancer continue to trend upwards by age: https://www.cancerresearchuk.org/health-professional/cancer-...

If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred.

> Why do you think that?

Because it is a truism. If they lived as long without cancer as everyone else, they per definition are not more susceptible. It's simply a restating of what being more susceptible implies.

> If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred.

This does not logically follow. This assumes that removing people with a genetic or other predisposition for getting cancer early would reduce the average risk of cancer more than increasing age increases it.

Mortality rates compounds. Reducing your average risk of dying of a given cause by even a tiny proportion on a per-year basis adds up to substantial chances of surviving longer.

That is fascinating. With a bit of imagination that could be terrifying if that were mostly a cohort effect (since it’s from a short number of years).
This reminds me of the US military vet that passed a few years ago at over 110 years old, with a life full of indulging in whiskey and cigars. His name is Richard Overton. [1]

It is clear how an individual may come to believe that this man’s genes were/are quantifiably better than others in these regards, due to how his body responded to - and managed - his long term intake of alcohol and tobacco, including the unspoken harmful ingredients.

Thought for the future: What follows the comprehensive identification of ideal traits and their genetic code..? Will “designer babies” become a new normal..?

[1]: https://www.cnbc.com/2018/12/28/richard-overton-dies-at-the-...

There was an story in Stephen Baxter's "Vacuum Diagrams" about a eugenics experiment where the participants could only reproduce at like 40 years, then 50, then 60, etc.

The leader was trying to suppress the genes that prevented long life. They probably did some nasty stuff to preserve the experiment, but it's not as bad as just killing all the babies that don't meet the standard of some puritanical leader.