Thread

1. dyauspitr · 1790966547 · focus · HN ↗

   So chronic stress is one of the main contributors to aging. I hope I make it to my 40s.

   Do we currently have the ability to do targeted methylation or de methylation at sites in cells?

   1. Chance-Device · 1790971024 · focus · HN ↗

      > Do we currently have the ability to do targeted methylation or de methylation at sites in cells?

      No, and you probably wouldn’t want it if you could. You don’t know what mutations are lurking in the genes that have been switched off or the consequences of turning them back on.

      I’ve thought about this a bit, and what resetting the methylation map really requires, in addition to actually resetting that map, is resetting your genome to a known good state.

      That’s pretty radical, but to selectively switch methylation on and off with precision you’re already talking about science beyond anything we have, featuring custom engineered constellations of proteins that unwrap your chromatin from around histones and then walk along it changing methylation state, then pack everything back.

      And doing it for each cell type, without applying the wrong map anywhere.

      And knowing what all the cell types and their correct methylation maps actually are.

      And assuming that methylation isn’t used anywhere, for example in the brain, in a way we don’t expect.

      And methylation isn’t the only kind of epigenetic modification.

      So, if we’ve solved all of those problems, rebuilding your DNA to a clean, mutation free state at the same time should be a breeze.

      We really do need AI for this if any of it is going to be remotely feasible.

      1. shevy-java · 1790973182 · focus · HN ↗

         > We really do need AI for this if any of it is going to be remotely feasible.

         Would you give your life into the hands of AI skynet slop?

         I understand your rationale, of course, but I for one don't want big fat mega-corporations dictate over our life here. Naturally, all of this hinges whether AI can even solve this problem. I assume it can, but I doubt it can do so initially - and the legal implications are still enormous. I really am not ready to turn my hands to claude's gene therapy slop.

         1. Alive-in-2025 · 1791007085 · focus · HN ↗

            why do we need ai for this? Yes, it's hard, so is laying out millions of gates in a cpu, later billions. We did it with software, not necessarily ai.
         2. someonebaggy · 1791032205 · focus · HN ↗

            Useful things like AlphaFold are getting conflated with LLM slop machines under this single "AI" umbrella.
      2. yieldcrv · 1790973401 · focus · HN ↗

         in my futile searches for meaning I’ve wondered whether cancers in humans are a failsafe to something else or preventing something worse

         more specifically the lack of more failsafes seen in some other mammals are a reaction to something besides happenstance

         1. jhrmnn · 1790975932 · focus · HN ↗

            Cancer is the price we pay for complex multicellular life. It’s not a failsafe, it’s the failure of all failsafes to regulate cellular growth within an organism.

            1. yieldcrv · 1790985357 · focus · HN ↗

               Larger mammals with many more cells have additional protections against cancer

               Such as longer and more numerous telomeres

               Hence why the human situation stands out to me and can’t be reduced to “it just is“. Some other mammals have it worse though

               1. usrnm · 1791008902 · focus · HN ↗

                  Evolution doesn't care about individual organisms, it's all about reproduction. Our lifespan is enough to raise a few children and pass genes on, so, from the evolutionary point of view, it's adequate

                  1. yieldcrv · 1791010489 · focus · HN ↗

                     I understand, I'm equally frustrated when people including scientists say that something evolved for an environmental specialization, instead of the evolution being happenstance that may have incentivized more viable mutant offspring surviving until reproduction in that environment, but was not "for" anything.

                     and yes, so I understand that with human cancer, it tends to happen or advance after reproduction has already occurred so therefore those traits are not selected against. it's impossible to weed out with human mating strategies

                     I would just like to believe the cancer itself is an adaptation preventing something worse, but you're right, it doesn't work with the natural selection theory and so we just had a dead end to our survivability baked in, not so different than how the opposite phenomenon of senescence in cephalopods ends their lives

                     1. matthewdgreen · 1791029251 · focus · HN ↗

                        Everyone involved in this discussion understands that evolution doesn’t create things for a purpose, that it’s just the result of selection pressures. Everyone also uses the more active phrasing because it’s much more convenient. Unless you think you’re talking to someone who genuinely doesn’t understand the nature of the process, it’s not useful to be pedantic about it.

                        1. yieldcrv · 1791038020 · focus · HN ↗

                           We’re agreeing actually and not talking to you at all
                  2. TJSomething · 1791015918 · focus · HN ↗

                     There's the grandmother hypothesis that holds we could just not have menopause and reproduce more, but we don't because there's greater evolutionary advantage for having the elderly provide support to their kin. Maybe this type of kin selection is bounded by consanguinity though, and that limits the advantage? Or maybe population pressure discourages family units from getting too large?

                     1. yieldcrv · 1791038142 · focus · HN ↗

                        That’s the kind of evolutionary explanation that doesn’t fit natural selection at all in any time period

                        You would need to explain how populations who did those things were selected against

                        Instead of the more aligned reality that there was a random attractive or forceful menopausal mutant that popped out alot of babies or put alot of babies in others

                        speaking of attractive, what we see now is that older women are selected against and everything considered attractive is correlated to ability of carrying a pregnancy to term. which came first? impossible for me to say, would older women have many more pregnancies if the menopause never happened? the viable eggs would have still gone towards zero, unlike other mammals and beings

                  3. kakacik · 1791022017 · focus · HN ↗

                     Evolution doesn't care at all, its just environment pressures and whatever organisms do within it. It can very well lead to some dead ends and sub-optimal long term choices.

                     There will come time when we will grok all this 100% and then can setup whatever we want (its just a bunch of molecules acting predictably), but we are very far from there and there is no point discussing this even for our grandchildren. We will have cyberpunk implants way sooner.

                  4. someonebaggy · 1791032075 · focus · HN ↗

                     Evolution doesn't care about anything. Evolution is a descriptive force, not prescriptive. It boils down to the statement that things which copy themselves, we have lots of, which should seem almost like a tautology. It has no goal or purpose. It's an extremely random process and the apparent purposefulness is mostly just the result of that random walk having billions of years to run.
         2. Terr_ · 1790982796 · focus · HN ↗

            > wondered whether cancers in humans are a failsafe

            I don't think so, but in the context of theories that are more-interesting than "stuff just breaks sometimes", I'd like to suggest the atavistic aspect.

            Some cancers resemble a return towards unicellularity, as if "newer" multicellular rules have broken down. Not in any remotely-effective "our genes shall survive the dark times as goo" way, though.

         3. coderintherye · 1790983499 · focus · HN ↗

            Was actually a great article on this last week: <a href="https:&#x2F;&#x2F;dynomight.substack.com&#x2F;p&#x2F;liver" rel="nofollow">https:&#x2F;&#x2F;dynomight.substack.com&#x2F;p&#x2F;liver

            Discussion: <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=49832938">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=49832938

         4. woadwarrior01 · 1791015321 · focus · HN ↗

            It&#x27;s the other way around. Aging is the failsafe and cancer is the failure mode.
      3. [deleted] · 1790975469 · focus · HN ↗

         [deleted]

      4. alfiedotwtf · 1790989826 · focus · HN ↗

         Is “at the same time” a hard requirement?
      5. darubedarob · 1791008778 · focus · HN ↗

         [dead]

      6. anoncow · 1791027281 · focus · HN ↗

         We need more AI driven research

         1. tclancy · 1791045300 · focus · HN ↗

            What would the training data set be?

            1. HPsquared · 1791059943 · focus · HN ↗

               Some sort of horrific experimental laboratory.

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