[HN Gopher] People who live past 105 years old have genes that s...
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       People who live past 105 years old have genes that stop DNA damage
        
       Author : awb
       Score  : 105 points
       Date   : 2021-05-08 18:33 UTC (4 hours ago)
        
 (HTM) web link (www.newscientist.com)
 (TXT) w3m dump (www.newscientist.com)
        
       | medymed wrote:
       | 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.
        
         | medymed wrote:
         | 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.
        
           | londons_explore wrote:
           | Even 100+ year old people tend to end up in healthcare
           | settings for a short while before they die.
        
         | londons_explore wrote:
         | 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.
        
           | sxv wrote:
           | This sounds interesting, do you have any references for
           | further reading?
        
             | londons_explore wrote:
             | 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.
        
           | [deleted]
        
       | zmmmmm wrote:
       | Underlying SNP data, if anybody wants to play with it:
       | 
       | https://figshare.com/articles/dataset/Whole-genome_sequencin...
        
       | reasonattlm wrote:
       | 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.
        
       | kingsuper20 wrote:
       | That's actually interesting.
       | 
       | You have to wonder what low-hanging fruit is coming up by
       | combining mass sequencing with medical (and other) history.
        
         | babesh wrote:
         | I wonder whether some group will start some gene therapy based
         | on this research.
        
       | Aardwolf wrote:
       | Are the SNP's of this known?
        
         | zmmmmm wrote:
         | 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.
        
       | andrewtbham wrote:
       | another source without paywall.
       | 
       | https://www.sciencedaily.com/releases/2021/05/210504112619.h...
        
         | flobosg wrote:
         | The journal's press release: https://elifesciences.org/for-the-
         | press/53c636fb/do-people-a...
         | 
         | The actual paper: https://elifesciences.org/articles/57849
        
       | azinman2 wrote:
       | 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...
        
         | hellbannedguy wrote:
         | 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?
        
           | o-__-o wrote:
           | No one makes it out alive
        
         | [deleted]
        
         | grishka wrote:
         | 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.
        
           | tasty_freeze wrote:
           | 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.
        
             | grishka wrote:
             | 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.
        
           | hellotomyrars wrote:
           | 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.
        
             | orangecat wrote:
             | _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.
        
             | true_religion wrote:
             | 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.
        
               | hellotomyrars wrote:
               | 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.
        
           | balfirevic wrote:
           | 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?
        
           | donio wrote:
           | How foolish. May you live forever is how I would curse my
           | worst enemies.
        
             | JohnJamesRambo wrote:
             | Curse me then.
        
           | chias wrote:
           | I like to imagine that this is what cells think right before
           | they become cancerous.
        
           | SvenMarquardt wrote:
           | 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.
        
           | crimson_chin wrote:
           | 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?
        
             | grishka wrote:
             | 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?
        
               | pizza wrote:
               | There are things worse than dying, similarly, there are
               | things that are better than what can be experienced
        
               | jlokier wrote:
               | 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.
        
               | grishka wrote:
               | > 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.
        
           | spiderice wrote:
           | May I ask why you are so confident? Sounds very sci-fi,
           | though I'd love for it to be true.
        
           | schnebbau wrote:
           | Do you have sources or reading material to substantiate your
           | confidence? I'm interested in this area.
        
             | grishka wrote:
             | 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=PLLvA7pB41pDk2
             | 7XOjqbXi...
        
               | fighterpilot wrote:
               | Imagine the misfortune of being 80 years old when
               | humanity finally figured out how to do this.
        
               | true_religion wrote:
               | 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.
        
               | notahacker wrote:
               | The worst would be discovering we can cure old age, but
               | only for people rich enough to pay for the
               | extraordinarily expensive treatment...
        
               | grishka wrote:
               | No, imagine the fortune because you'll now have your body
               | reverted to a younger age.
        
               | fighterpilot wrote:
               | 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
        
               | grishka wrote:
               | 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)
        
               | I-M-S wrote:
               | You got it in reverse: evolution only "cares" about the
               | individual
               | 
               | https://en.wikipedia.org/wiki/The_Red_Queen:_Sex_and_the_
               | Evo...
        
               | yosito wrote:
               | 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.
        
           | anotha1 wrote:
           | 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.
        
           | xwdv wrote:
           | We are going to die and never come back, 100%.
        
           | jtchang wrote:
           | The societal ramifications of a large number of people living
           | past 100 would be unprecedented.
        
             | bspammer wrote:
             | 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.
        
             | grishka wrote:
             | 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.
        
             | ben_w wrote:
             | 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.
        
         | [deleted]
        
         | jjtheblunt wrote:
         | 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?
        
           | azinman2 wrote:
           | 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.
        
             | virtue3 wrote:
             | 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/
        
             | londons_explore wrote:
             | 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?
        
         | [deleted]
        
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