5 ms·

Don't see how that contradicts anything GP said. "Aging bad, genetic diseases worse" - that's the gist of the disscussion here.

by 988747 4y ago

moralestapia 4y ago
>Aging is failure to follow the genetic plan faithfully due to breakdown of various epigenetic processes. This is not aging. That's the point I'm making.
- nicoburns 4y ago
  What do you think aging is? I was under the impression that there is evidence that aging is due to degradation of cell DNA over time, even if this isn't known conclusively at this time.
  - tux3 4y ago
    My impression is that all the aging talk the last several years seems to have been centered around epigenetics, senescent cells, other topics aside from just DNA mutations. It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. Your cells know how to replicate themselves without inheriting the accumulated damage, or any of the markers of aging. The parent cells do accumulate mutations, and with it an increased risk of cancer. But as soon as the reset switch is hit, we start back at zero. In the embryo, telomeres are long again, and cancer risk is low. Everywhere else in the parent's cells, aging continues unabated. If aging is DNA degradation, isn't it weird how aging isn't inherited?
    - nicoburns 4y ago
      > It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. My understanding is that this is one of primary purposes of gametes (eggs and sperm). That the body does have the ability to repair DNA (the testes do this during sperm production), but that it's very energy intensive. It does make sense that from an evolutionary perspective, individuals living longer may not actually contribute (and may actually be a detriment) to species fitness past a certain point.
      - tux3 4y ago
        If a near-perfect repair capability were available, I can't see that it would be very costly to the body to, for instance, use it on stem cells, progenitor cells, any -blast sufficiently up the hierarchy. I can't see it being all that energy intensive. It seems to me that DNA manipulation is relatively efficient, double-stranded break repairs via homologous recombination or NHEJ is in every cell. Bread and butter for your skin cells. And surely the energy consumption of all the turnover in epidermal cells alone would vastly overshadows the hypothetical cost of DNA repair in -blasts? We further spend serious amounts of energy on the immune system, on the brain, on all sorts of things, and we have good energy regulation mechanisms. Compared to all the things the body already does, spending energy on DNA repair seems like an excellent trade, when not actively underfed. I'm also suspicious of the argument that individuals living longer would be a detriment. DNA repair would not just cause longer life in the sense of very old people sticking around longer. It'd mean individuals living healthier lives for longer, so that they may still contribute to society, take care of grandkids, etc. Raising children is a big cost. If people lived longer healthy lives, arguably they could afford to have kids later if they chose to, which I imagine would save resources (e.g. by having a smaller percentage of life being spent in infancy and growth), potentially increasing fitness? A different argument still is that the body seems to have evolved many mechanisms to prevent cancer and to fight it when it happens. It seems that there has been selection pressure in the direction against DNA damage being a cause of death. If there were fitness in making people live shorter lives, I'd expect the body to try to do this not by letting DNA damage accumulate, but by trying to keep people as healthy as possible during their life, then separately using a programmed end-of-life to enforce a limit. I can't find the reason why this would be significantly hard for evolution to come up with, aside from the pristine DNA repair mechanism actually existing as described, which I don't think is really the case, no?
    - graphe 4y ago
      Aging isn't inherited? Older women's eggs make more children who are more likely to be retarded. Older men's make more children who more likely are taller, more prone to obesity, and schizophrenic. You don't start at zero. If your parents aren't healthy you likely won't be either. If you parents have undamaged eggs or sperm youll inherit more of your grandfathers traits from the x chromosome. If not you'll get my father's mutations.
      - tux3 4y ago
        That's true to an extent, yes. Hoewer if aging were inherited in a meaningful sense, the species would not have survived very long. My point behind this is that DNA mutations are normally inherited, and indeed we also see that older parents' children have higher risk. But that aging still almost entirely resets suggest that most of the effects of aging are not just plain DNA mutations. Hence the idea that it must be mainly something else that is not inherited, like epigenetics, senescent cells, etc
        graphe 4y ago
        We know it's not just DNA mutations, but you're conflating that with curing aging. More intelligent octopuses live for shorter periods of time, as do cuttlefish. The gene makes them intelligent as well as die sooner. Their species doesn't need long lifespans and it also isn't aging unnaturally long. Humans can age longer because they delay death at the cost of their genetic coding. Unless you're stopping this sooner rather than later it will be for nothing. Unfortunately the person I considered an expert on this is now blacklisted. He was more interested in reversing aging rather than delaying these effects, by removing all the mitochondria. Have you looked into the mitomouse?
        tux3 4y ago
        I'll google that, thank you.
  - moralestapia 4y ago
    If you let some food outside it'll rot. The thermodynamyc arrow only goes forward and humans are subject to that as well. Our body has some mechanisms to cope with that but they're not perfect, those residual issues + time is aging, IMO.

Don't see how that contradicts anything GP said. "Aging bad, genetic diseases worse" - that's the gist of the disscussion here.

by 988747 4y ago

Don't see how that contradicts anything GP said. "Aging bad, genetic diseases worse" - that's the gist of the disscussion here.

moralestapia 4y ago

>Aging is failure to follow the genetic plan faithfully due to breakdown of various epigenetic processes. This is not aging. That's the point I'm making.

nicoburns 4y ago
What do you think aging is? I was under the impression that there is evidence that aging is due to degradation of cell DNA over time, even if this isn't known conclusively at this time.
- tux3 4y ago
  My impression is that all the aging talk the last several years seems to have been centered around epigenetics, senescent cells, other topics aside from just DNA mutations. It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. Your cells know how to replicate themselves without inheriting the accumulated damage, or any of the markers of aging. The parent cells do accumulate mutations, and with it an increased risk of cancer. But as soon as the reset switch is hit, we start back at zero. In the embryo, telomeres are long again, and cancer risk is low. Everywhere else in the parent's cells, aging continues unabated. If aging is DNA degradation, isn't it weird how aging isn't inherited?
  - nicoburns 4y ago
    > It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. My understanding is that this is one of primary purposes of gametes (eggs and sperm). That the body does have the ability to repair DNA (the testes do this during sperm production), but that it's very energy intensive. It does make sense that from an evolutionary perspective, individuals living longer may not actually contribute (and may actually be a detriment) to species fitness past a certain point.
    - tux3 4y ago
      If a near-perfect repair capability were available, I can't see that it would be very costly to the body to, for instance, use it on stem cells, progenitor cells, any -blast sufficiently up the hierarchy. I can't see it being all that energy intensive. It seems to me that DNA manipulation is relatively efficient, double-stranded break repairs via homologous recombination or NHEJ is in every cell. Bread and butter for your skin cells. And surely the energy consumption of all the turnover in epidermal cells alone would vastly overshadows the hypothetical cost of DNA repair in -blasts? We further spend serious amounts of energy on the immune system, on the brain, on all sorts of things, and we have good energy regulation mechanisms. Compared to all the things the body already does, spending energy on DNA repair seems like an excellent trade, when not actively underfed. I'm also suspicious of the argument that individuals living longer would be a detriment. DNA repair would not just cause longer life in the sense of very old people sticking around longer. It'd mean individuals living healthier lives for longer, so that they may still contribute to society, take care of grandkids, etc. Raising children is a big cost. If people lived longer healthy lives, arguably they could afford to have kids later if they chose to, which I imagine would save resources (e.g. by having a smaller percentage of life being spent in infancy and growth), potentially increasing fitness? A different argument still is that the body seems to have evolved many mechanisms to prevent cancer and to fight it when it happens. It seems that there has been selection pressure in the direction against DNA damage being a cause of death. If there were fitness in making people live shorter lives, I'd expect the body to try to do this not by letting DNA damage accumulate, but by trying to keep people as healthy as possible during their life, then separately using a programmed end-of-life to enforce a limit. I can't find the reason why this would be significantly hard for evolution to come up with, aside from the pristine DNA repair mechanism actually existing as described, which I don't think is really the case, no?
  - graphe 4y ago
    Aging isn't inherited? Older women's eggs make more children who are more likely to be retarded. Older men's make more children who more likely are taller, more prone to obesity, and schizophrenic. You don't start at zero. If your parents aren't healthy you likely won't be either. If you parents have undamaged eggs or sperm youll inherit more of your grandfathers traits from the x chromosome. If not you'll get my father's mutations.
    - tux3 4y ago
      That's true to an extent, yes. Hoewer if aging were inherited in a meaningful sense, the species would not have survived very long. My point behind this is that DNA mutations are normally inherited, and indeed we also see that older parents' children have higher risk. But that aging still almost entirely resets suggest that most of the effects of aging are not just plain DNA mutations. Hence the idea that it must be mainly something else that is not inherited, like epigenetics, senescent cells, etc
      - graphe 4y ago
        We know it's not just DNA mutations, but you're conflating that with curing aging. More intelligent octopuses live for shorter periods of time, as do cuttlefish. The gene makes them intelligent as well as die sooner. Their species doesn't need long lifespans and it also isn't aging unnaturally long. Humans can age longer because they delay death at the cost of their genetic coding. Unless you're stopping this sooner rather than later it will be for nothing. Unfortunately the person I considered an expert on this is now blacklisted. He was more interested in reversing aging rather than delaying these effects, by removing all the mitochondria. Have you looked into the mitomouse?
        tux3 4y ago
        I'll google that, thank you.
- moralestapia 4y ago
  If you let some food outside it'll rot. The thermodynamyc arrow only goes forward and humans are subject to that as well. Our body has some mechanisms to cope with that but they're not perfect, those residual issues + time is aging, IMO.