4 ms·

Unlocking the secrets of myelin repair

102 points by kryster 3y ago

msie 3y ago
“infusing aged animals with cerebrospinal fluid from younger mice can boost SRF activation and actin assembly to more youthful levels” It seems like we should transplant more than organs.
- yosito 3y ago
  We could all become vampires. The old consuming the young to prolong life and youth. It's a common theme in science fiction and fantasy.
  - atmavatar 3y ago
    We've already seen the wealthy consume the blood of the young (in the form of transfusions) to try and live longer. See: https://www.bbc.co.uk/bbcthree/article/347828f8-6e7f-4a9b-92ab-95f637a9dc2e https://www.bbc.co.uk/bbcthree/article/347828f8-6e7f-4a9b-92...
  - hinkley 3y ago
    Elizabeth Bathory
    - hoseja 3y ago
      That was all (very successful) slander to oust a female heir out of her fief btw.
- collegeburner 3y ago
  this poses a huge risk of creating a prion epidemic. things like CSF are very, very risky
  - tomcam 3y ago
    Underrated comment
  - ChadNauseam 3y ago
    A larger risk than that which comes from blood transfusions? It seems like prion diseases tend to be brain-based, but I'm not sure why
    - arghwhat 3y ago
      The prion protein, which is the specific protein that can misfold to cause prion disease, is vastly more abundant in nervous tissue.
  - the8472 3y ago
    So we should only drink the blood and spinal fluid of newborns grown in vats and carefully monitored to make sure that they only contain healthy proteins.
  - RobotToaster 3y ago
    My guess is they don't actually want to do this on humans. This is just the first step, finding out if something in young CSF works. Next you figure out exactly what component of it is responsible, and figure out how to synthesise it.
  - GordonS 3y ago
    I have small fibre neuropathy, and living with constant pain is... hard - I'd personally take the odds.
  - Y_Y 3y ago
    Having seen the harrowing Japanese documentary series Shingeki no Kyojin, prions are the least of my worries.
    - arghwhat 3y ago
      Just make sure to screen any donors for Eldian ancestry.
- hfucvyv 3y ago
  I'd donate for MS patients even if it was just a temporary solution.
- OneLeggedCat 3y ago
  Peter Thiel emphatically nods head in agreement
- mullingitover 3y ago
  Didn't we go through this with youthful blood and find that simply diluting with saline and albumin had the same effect?
  - canadiantim 3y ago
    Source?
    - saurik 3y ago
      I copy/pasted the exact text of the comment you are responding to into Google--including the "Didn't we" and the question mark--and it pulled up the source you couldn't find. https://www.economist.com/technology-quarterly/2023/09/25/what-the-young-can-give-to-the-old https://www.economist.com/technology-quarterly/2023/09/25/wh... > In 2020 Irina Conboy of the University of California, Berkeley, and her colleagues found that replacing half of an old mouse's blood with just albumin, a blood protein, and saline solution had the same rejuvenating effect as young-mouse blood. Old blood may need filtering and dilution, not supplementing. https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-rejuvenates-tissue-reverses-aging-in-mice https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-r...
      - msie 3y ago
        I hope it doesn’t take 10 years for this therapy to be used! Cmon!
java-man 3y ago
Biorxiv preprint: [0] https://www.biorxiv.org/content/10.1101/2022.09.21.508765v1.full.pdf https://www.biorxiv.org/content/10.1101/2022.09.21.508765v1....
trdtaylor1 3y ago
Now I want to see the same but with near-adjacent chemicals. Is it SRF, or do the other closely related ones for repair and rejuvenation do it as well, just entering at a different stage. nmn, sirtuins, etc
madmod 3y ago
The fact that these are fatty tissues in the brain makes me concerned that ozempic might cause long term myelin damage.
- robbiep 3y ago
  I’m a doctor and familiar with the mechanism of both ozempic, to the extent it is known, and fat metabolism generally. I can’t see any connection between ozempic and myelin damage except you now know fat metabolism is involved. Is there something I am missing?
  - tsoukase 3y ago
    No worries. Myelin sheath is never catabolized for energy. It is far more valuable and protected behind solid mechanisms. The heart will stop long before. The only non-inflammatory cause of myeline damage is due to acute serum sodium changes, totally unrelated to fat metabolism. So Ozempic is pretty safe in that regard
- crakenzak 3y ago
  Hmm, valid concern but GLP1-RAs reduce fat (primarily) by better glycemic control and satiation. Unless if you're on Ozempic until you literally dry out every single fat reserve in your body and your brain has to resort to breaking down the myelin sheaths (something that can happen in ultra long distance running, hence why hallucinations sometimes happen on 100+ mile runes), then the GLP1-RAs wouldn't be able to force the body to break down the fat in the brain. To the best of my knowledge, GLP-1's have 0 direct impact on brain fat metabolism or myelin sheath breakdown. Side note, GLP1 based therapies are being investigated for improving brain health and potentially helping prevent the development of neurodegenerative illnesses, potentially because of an anti inflammatory feedback mechanism it activates when its able to reach tissues outside the gut. (natural GLP1 is usually broken down ~5 min in the body after release)
  - GenerWork 3y ago
    >dry out every single fat reserve in your body and your brain has to resort to breaking down the myelin sheaths (something that can happen in ultra long distance running, hence why hallucinations sometimes happen on 100+ mile runes) I've never heard of this before today, but if it's true then that's terrifying.
samstave 3y ago
So this piqued my curiosity as it reminded me of something I read regarding the differences btwn male and female myelination whereas the sheath develops in males "from the inside out" and in females "from the outside in" I found this interesting when I heard it... But MS presents in females vs males at 3:1 according to the MS society. Whats interesting is this article from NIH >"Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination" [0] it discusses the enzyme-like activities of nanomaterials, specifically how the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals The first sentence is pretty unpackable to some interesting "huh." moments: Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor (AR), have been only poorly studied in females who make low androgen levels But the Stanford study identified SRF (serum response factor) as a pivotal regulator of the genes involved in the cellular structure of oligodendrocytes—the glial cells responsible for myelinating nerve fibers in the brain and spinal cord. The Nature study goes on about nanozymes and how they may be able to affect remelination. [1] This NIH study discusses the gender differences of presenting MS in male/female rats as it pertains to where MS markers are found, whereas in females its found in spinal, but in males in the cerebellum... So if the growth of myelin is different in females than males, the markers occur in a gender dependent manner, and MS presents 3:1 females - its the myelination's development order thats calling out for observation... I looked up the etymology of myelin - and intersingly: >’: The ‘my’ in ‘myelin’ comes from the Greek word ‘myelos’ which means ‘marrow’ or 'the innermost part’. So, ‘myelin’ refers to the soft material found in nerve tissues." So as it was mentioned that females develop from the outside in, and myelin is the innermost soft tissue in the nerve, and MS present in females 3:1 - is this just all coincidence or is it just me? - Anecdote. when my daughter was a toddler, we kept catching her getting into the fridge and eating gobs of butter. I called my grandmother a life-long surgical nurse to ask if this was odd. She said "Heck no! Let her do it. Her brain is telling her she needs fats for development. Its good for her brain" - Shes wicked smart now. (but Ill take credit for the genes :-) [0] - https://www.nature.com/articles/s41467-023-36846-w https://www.nature.com/articles/s41467-023-36846-w [1] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282645/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282645/

102 points by kryster 3y ago

msie 3y ago

“infusing aged animals with cerebrospinal fluid from younger mice can boost SRF activation and actin assembly to more youthful levels” It seems like we should transplant more than organs.

yosito 3y ago
We could all become vampires. The old consuming the young to prolong life and youth. It's a common theme in science fiction and fantasy.
- atmavatar 3y ago
  We've already seen the wealthy consume the blood of the young (in the form of transfusions) to try and live longer. See: https://www.bbc.co.uk/bbcthree/article/347828f8-6e7f-4a9b-92ab-95f637a9dc2e https://www.bbc.co.uk/bbcthree/article/347828f8-6e7f-4a9b-92...
- hinkley 3y ago
  Elizabeth Bathory
  - hoseja 3y ago
    That was all (very successful) slander to oust a female heir out of her fief btw.
collegeburner 3y ago
this poses a huge risk of creating a prion epidemic. things like CSF are very, very risky
- tomcam 3y ago
  Underrated comment
- ChadNauseam 3y ago
  A larger risk than that which comes from blood transfusions? It seems like prion diseases tend to be brain-based, but I'm not sure why
  - arghwhat 3y ago
    The prion protein, which is the specific protein that can misfold to cause prion disease, is vastly more abundant in nervous tissue.
- the8472 3y ago
  So we should only drink the blood and spinal fluid of newborns grown in vats and carefully monitored to make sure that they only contain healthy proteins.
- RobotToaster 3y ago
  My guess is they don't actually want to do this on humans. This is just the first step, finding out if something in young CSF works. Next you figure out exactly what component of it is responsible, and figure out how to synthesise it.
- GordonS 3y ago
  I have small fibre neuropathy, and living with constant pain is... hard - I'd personally take the odds.
- Y_Y 3y ago
  Having seen the harrowing Japanese documentary series Shingeki no Kyojin, prions are the least of my worries.
  - arghwhat 3y ago
    Just make sure to screen any donors for Eldian ancestry.
hfucvyv 3y ago
I'd donate for MS patients even if it was just a temporary solution.
OneLeggedCat 3y ago
Peter Thiel emphatically nods head in agreement
mullingitover 3y ago
Didn't we go through this with youthful blood and find that simply diluting with saline and albumin had the same effect?
- canadiantim 3y ago
  Source?
  - saurik 3y ago
    I copy/pasted the exact text of the comment you are responding to into Google--including the "Didn't we" and the question mark--and it pulled up the source you couldn't find. https://www.economist.com/technology-quarterly/2023/09/25/what-the-young-can-give-to-the-old https://www.economist.com/technology-quarterly/2023/09/25/wh... > In 2020 Irina Conboy of the University of California, Berkeley, and her colleagues found that replacing half of an old mouse's blood with just albumin, a blood protein, and saline solution had the same rejuvenating effect as young-mouse blood. Old blood may need filtering and dilution, not supplementing. https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-rejuvenates-tissue-reverses-aging-in-mice https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-r...
    - msie 3y ago
      I hope it doesn’t take 10 years for this therapy to be used! Cmon!

java-man 3y ago

Biorxiv preprint: [0] https://www.biorxiv.org/content/10.1101/2022.09.21.508765v1.full.pdf https://www.biorxiv.org/content/10.1101/2022.09.21.508765v1....

trdtaylor1 3y ago

Now I want to see the same but with near-adjacent chemicals. Is it SRF, or do the other closely related ones for repair and rejuvenation do it as well, just entering at a different stage. nmn, sirtuins, etc

madmod 3y ago

The fact that these are fatty tissues in the brain makes me concerned that ozempic might cause long term myelin damage.

robbiep 3y ago
I’m a doctor and familiar with the mechanism of both ozempic, to the extent it is known, and fat metabolism generally. I can’t see any connection between ozempic and myelin damage except you now know fat metabolism is involved. Is there something I am missing?
- tsoukase 3y ago
  No worries. Myelin sheath is never catabolized for energy. It is far more valuable and protected behind solid mechanisms. The heart will stop long before. The only non-inflammatory cause of myeline damage is due to acute serum sodium changes, totally unrelated to fat metabolism. So Ozempic is pretty safe in that regard
crakenzak 3y ago
Hmm, valid concern but GLP1-RAs reduce fat (primarily) by better glycemic control and satiation. Unless if you're on Ozempic until you literally dry out every single fat reserve in your body and your brain has to resort to breaking down the myelin sheaths (something that can happen in ultra long distance running, hence why hallucinations sometimes happen on 100+ mile runes), then the GLP1-RAs wouldn't be able to force the body to break down the fat in the brain. To the best of my knowledge, GLP-1's have 0 direct impact on brain fat metabolism or myelin sheath breakdown. Side note, GLP1 based therapies are being investigated for improving brain health and potentially helping prevent the development of neurodegenerative illnesses, potentially because of an anti inflammatory feedback mechanism it activates when its able to reach tissues outside the gut. (natural GLP1 is usually broken down ~5 min in the body after release)
- GenerWork 3y ago
  >dry out every single fat reserve in your body and your brain has to resort to breaking down the myelin sheaths (something that can happen in ultra long distance running, hence why hallucinations sometimes happen on 100+ mile runes) I've never heard of this before today, but if it's true then that's terrifying.

samstave 3y ago

So this piqued my curiosity as it reminded me of something I read regarding the differences btwn male and female myelination whereas the sheath develops in males "from the inside out" and in females "from the outside in" I found this interesting when I heard it... But MS presents in females vs males at 3:1 according to the MS society. Whats interesting is this article from NIH >"Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination" [0] it discusses the enzyme-like activities of nanomaterials, specifically how the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals The first sentence is pretty unpackable to some interesting "huh." moments: Neuroprotective, anti-inflammatory, and remyelinating properties of androgens are well-characterized in demyelinated male mice and men suffering from multiple sclerosis. However, androgen effects mediated by the androgen receptor (AR), have been only poorly studied in females who make low androgen levels But the Stanford study identified SRF (serum response factor) as a pivotal regulator of the genes involved in the cellular structure of oligodendrocytes—the glial cells responsible for myelinating nerve fibers in the brain and spinal cord. The Nature study goes on about nanozymes and how they may be able to affect remelination. [1] This NIH study discusses the gender differences of presenting MS in male/female rats as it pertains to where MS markers are found, whereas in females its found in spinal, but in males in the cerebellum... So if the growth of myelin is different in females than males, the markers occur in a gender dependent manner, and MS presents 3:1 females - its the myelination's development order thats calling out for observation... I looked up the etymology of myelin - and intersingly: >’: The ‘my’ in ‘myelin’ comes from the Greek word ‘myelos’ which means ‘marrow’ or 'the innermost part’. So, ‘myelin’ refers to the soft material found in nerve tissues." So as it was mentioned that females develop from the outside in, and myelin is the innermost soft tissue in the nerve, and MS present in females 3:1 - is this just all coincidence or is it just me? - Anecdote. when my daughter was a toddler, we kept catching her getting into the fridge and eating gobs of butter. I called my grandmother a life-long surgical nurse to ask if this was odd. She said "Heck no! Let her do it. Her brain is telling her she needs fats for development. Its good for her brain" - Shes wicked smart now. (but Ill take credit for the genes :-) [0] - https://www.nature.com/articles/s41467-023-36846-w https://www.nature.com/articles/s41467-023-36846-w [1] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282645/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282645/