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Loss of cell identity drives human aging: Two new papers

369 points · 184 comments · bookofjoe

  1. egglinton · · focus · HN ↗
    These papers simply present the accumulated damage hypothesis with new window dressing. They do not account for the known facts.

    The article about these papers does not present a mechanism that would account for the Hayflick Limit.

    Nor does it explain why dogs, for example, age and die more quickly than humans. If there is a mechanism of epigenetic drift that would explain this, I do not see it in the article.

    The obvious answer to senescence is that we are programmed to do it. Cells die when they are supposed to die; if they don't, we have a problem.

    Likewise, mammals die when they are supposed to. It takes less time to train a puppy to survive on its own than it takes to train a human. Hence, dogs are optimized to age and die more quickly. It's better for the species.

    If we were not programmed to get old and die, evolution through natural selection would not work. We would never adapt to changing environments and our species would fail.

    Aging and death is not an accident or a deterioration from damage or a drift away from a correct instruction set. It is an absolute hard necessity, without which we would all be long gone.

    Stop wasting your time on nonsense articles like this and seek the mechanism that provides us as a species with the flexibility to adapt. Until we see aging and death as an core mechanism, we're going to be looking in the wrong place.

    1. LarsDu88 · · focus · HN ↗
      A lot of fallacies and assumptions in this comment. First of all there is nothing in biology or evolution where the "good of the species" has any kind of bearing on natural selection. This is the group selection hypothesis that has numerous counterexamples. If anything selection happens at the gene level over the long run.

      There is also no clear reason we know of yet as to why a human being couldn't simply reach sexual maturity and hunting age faster. In fact, there might be at least some evidence other hominids did reach sexual maturity faster. It is not fully understood why humans take so long, but in animal kingdom terms we take roughly as long as the Asian Elephant to reach reproductive maturity. Almost certainly a tradeoff for achieving greater brain development and intelligence, but this could also simply be the consequences of being intelligent (e.g. it's easier to evolve for bigger skulls once ape intelligence surpasses a threshold where the apes are capable of committing to greater early childcare such that natural selection in absence of intelligence is weakened).

      If dogs were optimized to age and die more quickly for the betterment of the canine species, then you could make the same argument for humanity. That's simply not what's going on. Human ancestors in the past who traded generation time for greater intelligence, likely selfishly outcompeted those who did not, and those other hominids either died off or represent a much smaller allelic contribution to the extant human gene pool.

      For evolutionary biologists, aging and death similarly likely represent evolutionary tradeoffs. After reaching sexual maturity, as the probability of producing more offspring declines, so too does natural selection as alluded to in the article. Women are born with their entire compliment of ova and the rate of errors increases dramatically as they get older. Men have similar but more subtle issues with sperm generation. These error rate absolutely can be driven by mechanical stresses over time, and I would imagine could be driving much of the selective pressure that puts a cap on human longevity in the long run.

      1. someonebaggy · · focus · HN ↗
        Selection happens at all levels simultaneously in one big chaotic mess. Cancer cells are evolutionarily successful until they are not.
    2. aksjfveoq · · focus · HN ↗

      [dead]

    3. jungturk · · focus · HN ↗
      "because they're supposed to" isn't a meaningful statement who is doing the supposing here? is this just an appeal to intelligent design?
    4. andrewflnr · · focus · HN ↗
      > If we were not programmed to get old and die, evolution through natural selection would not work. We would never adapt to changing environments and our species would fail.

      An arbitrarily long-lived organism can not only keep reproducing (think trees), thus increasing its share of the future gene pool, but can care for its descendants, increasing their survival and further amplifying its genes. Besides, even without senescence nothing would live forever: accidents, fights, and disease would take their toll. Avoiding these would just be an even stronger selection pressure than they are currently.

    5. jimberlage · · focus · HN ↗
      On a long enough timescale, things with a small chance of occurring become a virtual certainty. This includes the best of the human experience and the worst, which can get pretty dark.

      Why do people want to live forever?

      1. podocarp · · focus · HN ↗
        Fear, fear of the unknown, fear of death
        1. KronisLV · · focus · HN ↗
          > Fear, fear of the unknown, fear of death

          On one hand, death is the single most terrifying concept imaginable. In lieu of faith that explains it away, consider being conscious one moment, having been conscious most of your waking like and then it just ending. It being categorically different to the time before you existed, because you now exist. After passing away, never perceiving time, never having a thought, never experiencing anything, not even being aware of that and just being... gone. Forever.

          It doesn't sound peaceful to me, or like sleeping, or resting in any way. Instead, that's insanely fucked up, it being common or "inevitable" doesn't make it any less so.

          Like when my dad passed away, obviously I was sad about it happening and grieved it, at the same time I can acknwoledge that it was a small mercy that he wouldn't end up bedridden or trapped in a decaying body, and he didn't seem to fear it as much after having lived a long and fulfilling life and being religion-adjacent, but at the same time I very clearly don't like the idea of dying myself some day.

          So as far as I know, the only reasons for people to accept the concept of death and permanent nothingness is somewhere between either believing an "after" (and rejecting the possibility of it being a permanent end), being ignorant or indifferent about what it means (the non-solution of "Oh I'll just live on in the memories of other people" which completely doesn't concern your actual consciousness), or simply being more busy with their present lives and such, since it's generally far away.

          It rubs me the wrong way, that alongside with research towards more graceful aging (if not to say reversing it, curing cancer etc.) should be way more of a priority for all of humanity, instead of the current realpolitik bullshit. I don't lose much sleep over it, but a feeling of dread, it does evoke. Maybe I'll become even more ignorant with age, but I don't think that'd exactly be a conscious choice.

          1. podocarp · · focus · HN ↗
            I think what you're saying is you need purpose? So even with your dad not really fearing (or expressing his fear about) death you still feel that the benefits were him not having to suffer etc. etc.

            I think that's what religion gives, and it doesn't have to be organized religion. I'm not proselytizing, I'm just pointing out why across so many human cultures people always come up with stories and thoughts about the afterlife. The cold unknown means basically nothing and the fear I think comes from the nothingness -- imagine a life full of the sorrow and joys, and then it just vanishes. And worse of all, if nobody even remembers much it of it, it literally vanishes. For example if a war veteran never tells his experiences to anyone, he basically just vanished from earth and one can ask so did the things he went through happen? If a tree falls and nobody hears it and all that.

            I'm probably expressing it poorly but I've been thinking about it too after experiencing some loss too. In my case the person just graduated college. I think the dead have it easy, the suffering lies with the living…

      2. goatlover · · focus · HN ↗
        There is a vast amount of difference between growing old and dying by 100+ and living until the heat death of the Universe trillions of years from now. Surely something in between, say centuries or millenia without death from the ravages of old age would be ideal. Life is too short and tends to end in a bad way, would be nicer if it was a bit longer and more open ended without the decline until something fails.
        1. tclancy · · focus · HN ↗
          I wonder about this at 50. Being an odd duck, my philosophy here is based on a Conan story about a race that lived forever and had an actual ceremony for when the decided to end things.

          Stuff accretes over time. One shoulder, the opposite arm due to compensation, both big toes, etc. But take away all of that and there are still accretions: I’ve started to track the point where I know more dead people than live ones. Of course you can compensate for this and my wife and I have a wide social circle that we tend like good gardeners, but that feels like a delaying action. At some point I’m going to hit, “Hey, fellow kids!” if I haven’t already. Put more simply, will there come a time when the idea of falling in love with one more dog just to lose them will feel like a bad bet?

      3. someonebaggy · · focus · HN ↗
        Why do people want to die?

        I think if humans didn't age past 20, we'd still eventually get tired of life and want to die on our own terms instead of on a timer. We wouldn't stick around until the sun exploded.

    6. aeve890 · · focus · HN ↗

      [dead]

    7. NL807 · · focus · HN ↗
      >Aging and death is not an accident or a deterioration from damage or a drift away from a correct instruction set. It is an absolute hard necessity, without which we would all be long gone.

      Not buying this at all. This view is completely at odds against multicellular organisms that can literally clone themselves.

      Everything we know about aging so far points towards the deterioration of renewal mechanisms that keeps our system functional. Cells die due to a host of reasons besides programming. For example, they may become non-functional and eliminated by the immune system.

      1. someonebaggy · · focus · HN ↗
        But that deterioration seems to be programmed, or at least not selected against, which is surprising. We know animals with drastically different rates of aging, and some that are effectively immortal.
    8. goatlover · · focus · HN ↗
      There are giant tortoises that live longer than humans. I don't think they require a prolonged childhood for training to become successful adults. Perhaps the "programmed to die" is just an artifact of different evolutionary branches for some other biological reason.
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