[HN Gopher] People who live past 105 years old have genes that s... ___________________________________________________________________ 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] ___________________________________________________________________ (page generated 2021-05-08 23:01 UTC)