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.
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.
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.
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.
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.
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.
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…
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 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".
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?
> 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.
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.
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.
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.
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.
* 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.
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.
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.
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.
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?
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 ;-)
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.
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..?
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.
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.
Readit News
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 …).
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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.
Watch out - your insurance company would probably love that too, if they can get their hands on the data.
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/
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.
This happens shortly after Tesla makes the million full self driving robotaxis at the end of 2020?
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.
Fix one bug, say hello to another.
* 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.
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.
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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?
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https://figshare.com/articles/dataset/Whole-genome_sequencin...
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-...
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.
You have to wonder what low-hanging fruit is coming up by combining mass sequencing with medical (and other) history.