3 ms·

Is this aging or damage that looks like aging?

by m3kw9 4y ago

colechristensen 4y ago
Aging is a set of effects, in one sense of course it’s not aging if the time hasn’t actually passed but it seems that some of the same effects are happening.
- EGreg 4y ago
  Are you saying regular aging is due to damage rather than the genetic plan? Like prostate getting bigger etc.
  - MacsHeadroom 4y ago
    Aging is failure to follow the genetic plan faithfully due to breakdown of various epigenetic processes.
    - moralestapia 4y ago
      Nope. Diseases that have to do with "failure to follow the genetic plan [...]" are much more worse than aging, you don't even get to age!
      - 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?
robocat 4y ago
Aging is one side effect of a major internal system that counteracts cancers. Most of our cells are preprogrammed to die after a certain number of replications. This is one of many systems that counteract normal genetic mutations - which can cause cancers and other side effects. By definition a cancer has to reproduce and one way of defeating cancers is for cells to die (or be killed) once they reach a number of cell reproductions. Think of a binary tree where the tree depth is the number of cell reproductions, and telomere length controls tree depth. Each time a cell reproduces it risks mutations. Stem cells are the progenitor branches, and stem cells maintain “cleaner” copies of DNA, which then become normal cells. Normal cells then reproduce a number of times before they kill themselves. We have evolved this system because it balances the shorter term harms of cancer (high cost preventing reproduction), and senescence (lower cost after reproduction). There can be no “cure” for cancer, or aging. The cure would for cancer would require some way to either cause perfect cell reproduction, or to remove (or correct) all cells with imperfect reproductions. The “cure” for aging would require a cure for cancer. If I were to invest in something myself, it would be brain transplant, since brain cancers are rare, and dealing with organ rejection seems doable, and the issue of nerve reconnection seems solvable. The main problem is finding spare bodies, which can be unethically solved for a few wealthy people. The balanced-tree-depth metaphor makes me think of this: https://m.youtube.com/watch?v=plVk4NVIUh8 https://m.youtube.com/watch?v=plVk4NVIUh8 although admittedly it isn’t that relevant! Disclaimer: not a biologist.
- throwaway290 4y ago
  Would it still be you if only the brain is yours? Other organs like the gut play a big role in what we are like it turns out.
  - sockaddr 4y ago
    I think you might end up with a new array of moods and attentional dysfunctions, maybe some depression, but essentially it would still be you.
  - robocat 4y ago
    Are you still you after a head injury? After psychoactive drugs, prescription or not? Are you still you after a life-changing epiphany?
refurb 4y ago
This. The disease has many similarities to normal aging (wrinkles, blocked arteries) but many things that aren't (scleroderma, misshaped face). I think it's a mistake to assume that some treatment for progeria would be a treatment for aging in healthy humans.

Is this aging or damage that looks like aging?

by m3kw9 4y ago

Is this aging or damage that looks like aging?

Aging is a set of effects, in one sense of course it’s not aging if the time hasn’t actually passed but it seems that some of the same effects are happening.

EGreg 4y ago
Are you saying regular aging is due to damage rather than the genetic plan? Like prostate getting bigger etc.
- MacsHeadroom 4y ago
  Aging is failure to follow the genetic plan faithfully due to breakdown of various epigenetic processes.
  - moralestapia 4y ago
    Nope. Diseases that have to do with "failure to follow the genetic plan [...]" are much more worse than aging, you don't even get to age!
    - 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?

robocat 4y ago

Aging is one side effect of a major internal system that counteracts cancers. Most of our cells are preprogrammed to die after a certain number of replications. This is one of many systems that counteract normal genetic mutations - which can cause cancers and other side effects. By definition a cancer has to reproduce and one way of defeating cancers is for cells to die (or be killed) once they reach a number of cell reproductions. Think of a binary tree where the tree depth is the number of cell reproductions, and telomere length controls tree depth. Each time a cell reproduces it risks mutations. Stem cells are the progenitor branches, and stem cells maintain “cleaner” copies of DNA, which then become normal cells. Normal cells then reproduce a number of times before they kill themselves. We have evolved this system because it balances the shorter term harms of cancer (high cost preventing reproduction), and senescence (lower cost after reproduction). There can be no “cure” for cancer, or aging. The cure would for cancer would require some way to either cause perfect cell reproduction, or to remove (or correct) all cells with imperfect reproductions. The “cure” for aging would require a cure for cancer. If I were to invest in something myself, it would be brain transplant, since brain cancers are rare, and dealing with organ rejection seems doable, and the issue of nerve reconnection seems solvable. The main problem is finding spare bodies, which can be unethically solved for a few wealthy people. The balanced-tree-depth metaphor makes me think of this: https://m.youtube.com/watch?v=plVk4NVIUh8 https://m.youtube.com/watch?v=plVk4NVIUh8 although admittedly it isn’t that relevant! Disclaimer: not a biologist.

throwaway290 4y ago
Would it still be you if only the brain is yours? Other organs like the gut play a big role in what we are like it turns out.
- sockaddr 4y ago
  I think you might end up with a new array of moods and attentional dysfunctions, maybe some depression, but essentially it would still be you.
- robocat 4y ago
  Are you still you after a head injury? After psychoactive drugs, prescription or not? Are you still you after a life-changing epiphany?

refurb 4y ago

This. The disease has many similarities to normal aging (wrinkles, blocked arteries) but many things that aren't (scleroderma, misshaped face). I think it's a mistake to assume that some treatment for progeria would be a treatment for aging in healthy humans.