4 ms·

This is a finding more about cellular fatigue and might explain what fatigue actually is. The root cause of ME/CFS and Long Covid Fatigue is almost certainly a

This is a finding more about cellular fatigue and might explain what fatigue actually is. The root cause of ME/CFS and Long Covid Fatigue is almost certainly a chronic infection in tissue without much detectable presence in fluids making it difficult to identify and treat. It is an interesting finding since some treatments for ER stress exist and are worth testing. It's also somewhat linked to the Itaconate shunt theory that Robert Phair at Stanford has been investigating for the past year.

tomrod 3y ago
It's probably not COVID hiding in the tissues? I wonder whether injection of genes by the virii result in altered DNA producing broken proteins. Is 23andMe data of sufficient quality to test altered DNA?
- pja 3y ago
  23andme looks for specific single nucleotide polymorphisms (SNPs) so it’s completely unsuitable for looking for this kind of DNA alteration that could be anywhere in the genome.
  - tomrod 3y ago
    Thank you for the correction. How would you look for DNA alteration, generally?
    - mnw21cam 3y ago
      Whole genome sequencing of some kind, preferably one of the newfangled long-read technologies such as Oxford Nanopore or Pacbio, would be best for looking for novel insertions into the genome. However, this is likely to be a fool's errand in this case, because this kind of sequencing normally assumes that we can take a sample of many cells from the body, and that all those cells have the exact same DNA changes. If you have a mutation that is induced in a parent or the single-figure-cell stage of embryo development then that will be true, but for DNA modification by a virus in an adult it will not be. Each cell will have a different insertion. Now, there are some techniques that can sequence the DNA from a single cell, but they don't give quite as good quality data, and because you'd be wanting to sample a good number of cells to see what the distribution of insertions is, it will likely also be very expensive.
- francisofascii 3y ago
  > It's probably not COVID hiding in the tissues? It totally could be. Viral persistence is a strong suspect. HIV hides in "sanctuary" tissues. Other viruses and bacteria probably can evade the immune system in certain types of tissue.
londons_explore 3y ago
One potential mechanism for fatigue: * Virus' have a high failure rate - many infected cells never go on to multiply. * However, those infected cells may also not still perform correctly. * If you have a good chunk of your cells in your body no longer performing their function, yet not dying and making way for replacements either, everything isn't going to work as well. That would explain why it is a wide range of viruses that can all cause fatigue symptoms, and also why parasitic and bacterial infections rarely cause the same. Technical term: Virus-induced senescence
- rocqua 3y ago
  That seems like a plausible hypthosis, but hard to test for. In this hypothesis, what would be a solution? Best I can think of is Chemo-therapy, to kill of the bad cells. But that feels incredibly heavy handed, as well as liable to do more damage.
  - yldedly 3y ago
    Probably not a solution, but many people have reported benefits from fasting, which increases cellular autophagy which degrades disfunctional cell parts - and might play a role in programmed cell death, though the relationship is not clear.
  - lixtra 3y ago
    Intermittent fasting could work. And time.
  - alphazard 3y ago
    Two sibling comments mentioned fasting. Adding more to that. Prolonged fasting is known to clear away senescent cells. So that is the intervention which seems most promising here. Intermittent fasting can help the gut by giving it time to rest between meals, and it can improve insulin sensitivity because the body spends more time in a low insulin state. Maybe there are longer chains of mechanism there, but at first glance, they don't seem quite as relevant.
- FollowingTheDao 3y ago

tomrod 3y ago

It's probably not COVID hiding in the tissues? I wonder whether injection of genes by the virii result in altered DNA producing broken proteins. Is 23andMe data of sufficient quality to test altered DNA?

pja 3y ago
23andme looks for specific single nucleotide polymorphisms (SNPs) so it’s completely unsuitable for looking for this kind of DNA alteration that could be anywhere in the genome.
- tomrod 3y ago
  Thank you for the correction. How would you look for DNA alteration, generally?
  - mnw21cam 3y ago
    Whole genome sequencing of some kind, preferably one of the newfangled long-read technologies such as Oxford Nanopore or Pacbio, would be best for looking for novel insertions into the genome. However, this is likely to be a fool's errand in this case, because this kind of sequencing normally assumes that we can take a sample of many cells from the body, and that all those cells have the exact same DNA changes. If you have a mutation that is induced in a parent or the single-figure-cell stage of embryo development then that will be true, but for DNA modification by a virus in an adult it will not be. Each cell will have a different insertion. Now, there are some techniques that can sequence the DNA from a single cell, but they don't give quite as good quality data, and because you'd be wanting to sample a good number of cells to see what the distribution of insertions is, it will likely also be very expensive.
francisofascii 3y ago
> It's probably not COVID hiding in the tissues? It totally could be. Viral persistence is a strong suspect. HIV hides in "sanctuary" tissues. Other viruses and bacteria probably can evade the immune system in certain types of tissue.

londons_explore 3y ago

One potential mechanism for fatigue: * Virus' have a high failure rate - many infected cells never go on to multiply. * However, those infected cells may also not still perform correctly. * If you have a good chunk of your cells in your body no longer performing their function, yet not dying and making way for replacements either, everything isn't going to work as well. That would explain why it is a wide range of viruses that can all cause fatigue symptoms, and also why parasitic and bacterial infections rarely cause the same. Technical term: Virus-induced senescence

rocqua 3y ago
That seems like a plausible hypthosis, but hard to test for. In this hypothesis, what would be a solution? Best I can think of is Chemo-therapy, to kill of the bad cells. But that feels incredibly heavy handed, as well as liable to do more damage.
- yldedly 3y ago
  Probably not a solution, but many people have reported benefits from fasting, which increases cellular autophagy which degrades disfunctional cell parts - and might play a role in programmed cell death, though the relationship is not clear.
- lixtra 3y ago
  Intermittent fasting could work. And time.
- alphazard 3y ago
  Two sibling comments mentioned fasting. Adding more to that. Prolonged fasting is known to clear away senescent cells. So that is the intervention which seems most promising here. Intermittent fasting can help the gut by giving it time to rest between meals, and it can improve insulin sensitivity because the body spends more time in a low insulin state. Maybe there are longer chains of mechanism there, but at first glance, they don't seem quite as relevant.
FollowingTheDao 3y ago