Thread

1. rotbart · 1791018164 · focus · HN ↗

   The strongest evidence we have of the reversibility of epigenetic aging, as well as its limitations -- are embryos which undergo an epigenetic reset.

   After fertilisation, the embryo strips the father's DNA of its age-linked chemical tags and swaps its packaging, destroys his mitochondria, rebuilds telomeres, and clears damaged proteins, though it can't undo the DNA mutations sperm gather as men age.

   (those that result in an non viable embryo result in miscarriage.)

   1. jijijijij · 1791030973 · focus · HN ↗

      Embryogenesis is an early fail-fast process. The vast majority of mutations and instabilities are caught through developmental checkpoints. Every living human passed a ruthless selection process in the womb.

      So part of the magic of that aging reversal is simply abandoning what doesn't stick. You can't do that to a grown human, obviously.

      1. HexPhantom · 1791033466 · focus · HN ↗

         An adult therapy has to rejuvenate the cells you already have, in place, without breaking tissue function or creating cancer. Much less room for error

         1. jijijijij · 1791036682 · focus · HN ↗

            Yes, that's my point. Although, I wouldn't say "less room for error", but rather less room for handling error.

            Early embryogenesis seems to activate weird genetic pathways, whose function scientists suspect evolved for the sake of complexity alone, to be a genetic integrity stress test.

            Mind you, mutation in sexual reproduction isn't at all just accidental "bit flips". The cross-over stage in meiosis always recombines the chromosomal information randomly (to increase environmental adaptability, off-setting the slow rate of sexual reproduction). There is no concept of a "gene" there, the cuts can happen in the middle of anything important, too. This intentional instability needs to be accounted for, biologically.

            Before anyone even detects pregnancy, a lot of non-viable genetics have been aborted by the body. As tragic as they are for the becoming parents, miscarriages are a good thing, not misfortune. It's exactly this fail-fast selection process weeding out failed random recombination attempts, which likely would have caused severe functional problems later anyway.

            The body isn't a lump of omnipotent cells, but a complex system of functionally primed cells. You cannot do a selective genetic stress test on a developed organism like that. Without radical selection, the rejuvenation process wouldn't be safe, rather a guarantee for cancer and metabolic dysfunction. At any point in time, there are malignant cells somewhere in the body, which are constantly snatched by the immune system. In fact, "rejuvenation"/immortality is a hallmark of cancerous transformation. And let's not forget, embryonic development isn't fully self-governed. The mother's body also checks the embryo's signaling and may abort anything funky. A developed organism doesn't have this external oversight. Auto-immunity and genetic checkpoints is all there is and those mechanisms can become malignant, too.

            Did you know, with age, men's somatic cells increasing lack the whole Y-chromosome? It's not at all mission critical and just got lost at some point during mitosis, no biggie, but I think it shows the extent of accumulated genetic disarray in somatic cells.

            1. soyboy_supreme · 1791184543 · focus · HN ↗

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