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Blog Article: "Is the era of precision medicine for chronic fatigue syndrome at hand?"

Discussion in 'General ME/CFS News' started by Webdog, Sep 5, 2017.

  1. Webdog

    Webdog Senior Member

    This is beyond my knowledge level. But perhaps someone with the right background can comment on this article about an idea for testing and treatment for ME/CFS.

     
    Last edited: Sep 5, 2017
  2. perrier

    perrier Senior Member

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    This is fascinating. Someone please forward this to Dr Ron Davis. He is sure not to leave any stone unturned.
     
    dreampop likes this.
  3. Cam Newton

    Cam Newton

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    Not to nit pick, but the fatigue I experienced with mono feels like a very different type of fatigue I feel with ME/CFS. And I only had mono two years ago, which ended up triggering the ME/CFS. So I still remember it fairly well.
     
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  4. Snow Leopard

    Snow Leopard Hibernating

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    I don't really understand what the author of the article is saying - what is the specific hypothesis?

    Simply saying that a SASP is involved is too vague - there necessarily need to be extracellular feedback loops.
     
    MEMum likes this.
  5. viggster

    viggster Senior Member

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    Hutan, ukxmrv, JaimeS and 5 others like this.
  6. Learner1

    Learner1 Professional Patient

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    Tunguska, Barry53, Skycloud and 2 others like this.
  7. MEMum

    MEMum Senior Member

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    @JaimeS This sounds fascinating.

    The top reference, ie @viggster is about a guy blogging on fatigue states relating to senescent cells, ie those no longer dividing, but not dying either.
    He looks at the 74 pro-inflammatory molecules produced by senescent cells. These are known as SASP (Senescence Associated Secretory Phenotypes)

    He then compares the SASPs with the levels of 17 of the 51 cytokines correlated with severity of CFS. (PNAS)
    "So I looked up the individual elements of the SASP (which can be found in Annu Rev Pathol. 21010; 5: 99–118.) There are 74 of them. I wondered how many of the 51 cytokines measured in the PNAS paper were in the SASP. This is trickier than it sounds as many cytokines have far more than one name. The bottom line is that 20 SASPs are in the 51 cytokines measured in the paper.
    If the fatigue of CFS is due to senescent cells and the SASPs they release, then they should be over-represented in the 17 of the 51 cytokines correlating with symptom severity. Well they are; 9 out of the 17 are SASP. However although suggestive, this increase is not statistically significant (according to my consultants on Math Stack Exchange)."

    @Janet Dafoe (Rose49) as well, in case Jaime is still recovering from the amazing conference
    @Simon @Jonathan Edwards ...
     
  8. Wonko

    Wonko Senior Member

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    The other side.
    Obviously - give them a good talking to and explain the error of their ways - it's the only approved treatment after all.
     
  9. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I don't quite get how cells can be senescent in ME. If it was most cells then bits of you would die and they don't. If it is blood cells most of them die after a few days anyway. And he seems to have found 9 out of 17 cytokines - which is some but you would expect some I think. It doesn't click into place for me yet!
     
  10. MEMum

    MEMum Senior Member

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    Thanks for that info. I'm way out of my depth, but it seemed worth flagging it up to OMF/people who know more science than I do.

    Thanks for mentioning other thread @AndyPR . I would ask a moderator to merge the threads, but don't think it would be a priority at the moment! Have you ever thought of moderating Andy, you seem to have the necessary skills, technical abilities and understanding?
    Though I suspect that volunteers for moderating or being on the Board have nosedived significantly after recent events....
     
  11. MEMum

    MEMum Senior Member

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    I interpreted this as follows:
    The PNAS study shows that out of 51 cytokines measured, 17 correlate with fatigue/disease severity in ME.
    Of these 17 cytokines, 9 are the same as pro-inflammatory molecules that are produced by senescent cells. These are called SASPs (ie Senescence Associated Secretory Phenotypes). There are 74 of these produced by senescent cells,

    It appears that his original investigations into looking at SASPs arose from the fact that cancer cells which have been "zapped" by chemotherapy go into a senescent state and cancer patients who have had chemo are generally pretty fatigued.

    I may be getting this wrong, or reading too much into it, but the overlap seems worth flagging up to the OMF team and anyone else on here who is likely to have a better grasp of the science than I do.
     
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  12. Joh

    Joh Inactivist

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    [​IMG]
     
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  13. AndyPR

    AndyPR RIP PR :'(

    I've reported the two threads, asking for a merge. :)

    Thanks for the vote of confidence but as things stand currently I wouldn't even consider volunteering, sadly.
     
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  14. Alvin2

    Alvin2 If humans were rational...

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    I think the senescence-ME/CFS theory is nonsense, though here is some information and a simple treatment that anyone can try, you can get bioactive quercetin (EMIQ) that has high bioavailability but if it cures your ME/CFS i will be shocked. On the other hand Quercetin is a very interesting nutrient that has many other positive effects and even helps mice suffering from radiation induced damage (not in the article but from other research i have done in the past).
    http://www.lifeextension.com/Magazine/2015/SS/Sweep-Away-Senile-Cells/Page-01
     
    Last edited: Sep 11, 2017
  15. Tunguska

    Tunguska Senior Member

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    Always struck me as a possibility or contributing factor, e.g. closest I spotted:
    https://www.nature.com/onc/journal/v24/n11/full/1208262a.html
    (and others, https://www.ncbi.nlm.nih.gov/pubmed/20583212 etc.)
    and is involved in forms of muscle damage which is the initial clue.
     
  16. Tunguska

    Tunguska Senior Member

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    Hypothetical scenario:
    * p53 is a well-known inducer of senescence (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784259/)
    * part of TGF-beta/SMAD effects are mediated with p53 (https://www.hindawi.com/journals/jst/2012/294097/)
    * SIRT1 abolishes senescent effects of p53 (http://www.jbc.org/content/282/15/10841.full)
    * SIRT1 depends on NAD/NADH ratio (in part via circadian Nampt activity)
    * ergo, cells with low NAD/NADH ratio in the presence of elevated TGF-beta are more likely to be induced into senescence
    * Result: severely reduced cell turnover

    But it could be worse because there appear to exist non-p53 (and non-P16) mechanisms through which TGF-beta can induce senescence: https://www.ncbi.nlm.nih.gov/pubmed/21555587 https://www.ncbi.nlm.nih.gov/pubmed/20583212
    This is the most annoying part - it does seem like TGF-beta can override other pathways quite a lot. Means that diagnostic attempts with supplements might be futile.
     
    Last edited: Sep 20, 2017
  17. Tunguska

    Tunguska Senior Member

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  18. Tunguska

    Tunguska Senior Member

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    Well anyway, here's a picture that two-thirds represents what I'd pictured and visualizes part of what OP's author described (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253488/):
    embr0015-1139-f1 acute chronic senescent cells.jpg

    Senescent state itself is not organ death so I viewed it as a (muscle/etc) cell turnover issue on two levels, and immune system is supposed to do bulk of the clearance of the senescent cells.

    That said p53/p16/p21 appear impossibly complicated (cell fate decision is ascribed to p21 downstream of p53, with p16 contributing separately) and some of this picture's article's conclusions might circumstantially contradict some of what I conjured up for fun above with p53 deacetylation. That's without even a mention of TGF-beta that activates all this and more, since it's major mediator in wound healing.

    Obviously this is not concrete, but personally I'm with the OP author in feeling this is worth measuring or ruling out (first in severe).

    I skimmed the 2017 Cell article he referenced (sci-hub) and it's mostly familiar except some perplexing bits about macrophages themselves expressing senescence state, never thought about that...
     

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