Thread

Loss of cell identity drives human aging: Two new papers

369 points · 184 comments · bookofjoe

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. someonebaggy · 1791032000 · focus · HN ↗
    You can at the cellular level. There's a hypothesis that low levels of caloric restriction or oxidative stress are essential, because they weed out underperforming cells, which are replaced.
    pasquinelli · 1791033035 · focus · HN ↗
    do you mean to say low levels of caloric restriction, or low levels of caloric intake?
    someonebaggy · 1791039112 · focus · HN ↗
    A small amount of adverse conditions.
    tclancy · 1791045212 · focus · HN ↗
    If that works, just think what a heroic amount could do!
    wizzwizz4 · 1791045955 · focus · HN ↗
    It can weed out all your cells!
    meowkit · 1791046256 · focus · HN ↗
    Common response and completely misses the point. Its about dosage.
    Water will quench your thirst. You can also drown in it.
    Fire will warm your hands. Sticking you hands in a fire is a bad idea.
    Acute stress, induced by exercise / caloric restriction, is feedback to trigger beneficial cellular behavior.
    Chronic stress, no exercise / eating poorly through starvation or overconsumption (a “heroic dose”) will certainly kill you sooner.
    gozucito · 1791054057 · focus · HN ↗
    I think it was a joke :)
    jijijijij · 1791037243 · focus · HN ↗
    This is not at all comparable to the extent of embryonic rejuvenation. Lol.
    Caloric restriction etc. just aids cellular housekeeping. The processes in maintaining gametic immortality are much more radical and transformative. Somatic and gametic genetics are governed completely differently.
    agumonkey · 1791043442 · focus · HN ↗
    Do you have books or articles to read about this ?
    jijijijij · 1791049714 · focus · HN ↗
    All of it is a matter of active research, as this relates to the evolution of sex/sexual reproduction, which, contrary to popular belief, is still an unsolved problem in biology. Classical evolutionary theory cannot explain sexual evolution. Any book about "why?" will either be highly opinionated, agenda-driven, out-dated, or simplistic (as are my comments here).
    I am not a biologist, so I can not refer to or evaluate any meaningful recent papers on the matter. However, I can recommend the podcast 'Big Biology', which dives into current biology research, theory and philosophy, including sexual evolution.
    You may start here: <a href="https://en.wikipedia.org/wiki/Evolution_of_sexual_reproduction" rel="nofollow">https://en.wikipedia.org/wiki/Evolution_of_sexual_reproducti...
    Richard Dawkins' 'The Selfish Gene' is also an excellent read/audiobook. His specific theories of the evolutionary "unit" have been disproven, but his argumentation teaches a lot about "evolutionary thinking". I really wish he stuck with biology and science education instead of becoming this reactionary giga twat.
    agumonkey · 1791050866 · focus · HN ↗
    thanks a lot, i'll start with those.
    if you know other websites or podcasts similar to big biology i'd be glad, i've been trying to setup some list of sources on that topic
    thanks again
    jijijijij · 1791054227 · focus · HN ↗
    Sorry, it's not my main interest right now, so I am out-of-the-loop.
    Last time I checked, Big Biology was kinda unique going beyond basic popsci, while still remaining interesting and engaging. I think biologists are not the most technically inclined, not really drawn to podcasting. And it's also not the hottest of topics right now, specific research PR and educational voices aren't funded well. There are some journal/university etc. associated everybody-has-a-podcast-now podcasts, but I found them to be rather boring and dry. Individual episodes of the Huberman/Lex Fridman type edgelord podcasts may also be occasionally interesting, but the signal to noise ratio is poor, with a heavy bias towards overconfident and narcissistic guests speaking with false authority, lots of explanatory speculation presented as facts, pronounced political confirmation bias.
    Maybe take a well presented episode on Big Biology and see where else respective guests speak or publish?
    Ratelman · 1791053822 · focus · HN ↗
    What do you mean when you say sexual evolution?
    jijijijij · 1791056081 · focus · HN ↗
    The evolution of sex and sexual reproduction, as opposed to other means of reproduction. It is inherently tied to the difference in genetic maintenance/repair mechanisms between germline and somatic cells. See wiki link above.
    yrjrjjrjjtjjr · 1791064298 · focus · HN ↗
    Sexual reproduction can remove bad mutations. Imagine two parents. One has bad mutations m1. Other has bad mutation m2. They have three children. The first gets only m2. The second gets both and dies. The third inherits neither.
    Even though neither parent was fully healthy, one of the children was. Asexual reproduction cannot do this.
    jijijijij · 1791072763 · focus · HN ↗
    The scenario you are painting only exists with sexual reproduction, so it's circular reasoning.
    mitxela · 1791109888 · focus · HN ↗
    Organisms can only have bad mutations if they reproduce sexually?
    jijijijij · 1791124684 · focus · HN ↗
    No, of course not. But having diploid, paternal and maternal DNA is something you need sexual reproduction for.
    Apart from that, it's also wrong because sexual reproduction did not get rid of anything. Just one offspring not affected, but the premise already established the fitness of partial carriers, so that mutation is gonna remain in the gene pool.
    yrjrjjrjjtjjr · 1791134856 · focus · HN ↗
    Let me rephrase to be more neutral. Imagine two genetic lines. Both lines have one bad mutation. Survivable, but makes the individual less fit. With asexual reproduction evolution has to pick one or the other. With sexual it can get rid of both.
    jijijijij · 1791138142 · focus · HN ↗
    Why does evolution have to pick one of them?
    You are not really thinking this through. How would a fitness reducing mutation become a feature of a genetic line in the first place in asexual reproduction? The "silent" partial carrier dynamic of genetic defects is a problem exclusive to sexually reproducing organisms.
    How can sexual reproduction "get rid of them"?
    Play it out for a few generations, you will see, there is a frequency equilibrium. We've done this in school with paper, but if you know some programming, it's an easy exercise. Anyway, unless being very detrimental for partial carriers, the bad allele is gonna stay in the gene pool.
    mitxela · 1791144933 · focus · HN ↗
    Imagine a flax bush with a mutation that causes smaller leaves and a separate one that makes it live longer. Remember, mutations are completely random. In asexual reproduction it's probably going to be about as prevalent as the wild type (the default without these mutations). In sexual reproduction the repeated shuffling of genes will eventually (quite quickly in this case) produce one with the longer life but without the smaller leaves.
    jijijijij · 1791148590 · focus · HN ↗
    You are shifting the goalpost. It's not the original argument anymore.
    yrjrjjrjjtjjr · 1791172949 · focus · HN ↗
    > How would a fitness reducing mutation become a feature of a genetic line in the first place in asexual reproduction?
    A random mutation. Especially when combined with the founder effect or some other genetic bottlenecking.
    rsync · 1791056493 · focus · HN ↗
    I think the Nick Lane books are quite good - especially:
    <a href="https://en.wikipedia.org/wiki/Power,_Sex,_Suicide" rel="nofollow">https://en.wikipedia.org/wiki/Power,_Sex,_Suicide
    which, IIRC, discussed the notion of an semi-autonomous population of mitochondria in long lived tissues (like muscle) which could be curated over ones lifetime by high intensity exercise stress. Future mitochondria in these long-lived tissues would then not be descended from the poorer performing members who were weeded out through apoptosis.

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