[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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