WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome, 2023 Hwang et al

Given the importance of the interaction between the ER and mitochondria for muscle function, we reasoned that ER stress, also reported to play a role in rheumatic diseases which often feature fatigue, may regulate WASF3 in muscle cells. Indeed, the ER stress marker PERK was significantly higher while BiP was lower in the ME/CFS muscle samples. This discordance between PERK and BiP levels in ME/CFS samples suggested impairment of the canonical ER stress pathway, termed “ER Stress Response Failure,” which has been proposed to result in metabolic disorders (31).
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Ref 31 has a thread Endoplasmic Reticulum ER Stress Response Failure in Diseases (2020)
 
B_V said:
Paul Hwang used this 2011 paper to ID WASF3 as a gene product of interest.

I've written an article for The Washington Post about how this research came about - it's due to the tenacity of one woman who wanted answers to her own health problems - but August is the worst time of year for science & journalism & due to some factors outside my control it won't be published until next week at the earliest.
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Hey @B_V! As August comes to a close here, was just wondering if WP is still slated to publish this soon, from what you know? Thanks for sharing this with us.
 
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The NIH are highlighting this paper on their News & events.


Protein may be linked to exercise intolerance in ME/CFS
https://www.nih.gov/news-events/nih...ein-may-be-linked-exercise-intolerance-me-cfs

At a Glance
  • A study suggested that high levels of a protein may reduce energy production in the muscle cells of people with ME/CFS.
  • Blocking this protein in cells in the lab restored energy production, suggesting a potential new strategy for treating the condition.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) afflicts more than 2 million people nationwide. People with ME/CFS live with debilitating symptoms including exhaustion, exercise intolerance, cognitive problems, and a worsening of symptoms after even mild exertion (known as post-exertional malaise).​

The continued obstinate refusal by psychosomatic ideologues to acknowledge PEM is looking worse over time, but still their dam of obstruction is holding.
 
rvallee said:
The NIH are highlighting this paper on their News & events.


Protein may be linked to exercise intolerance in ME/CFS
https://www.nih.gov/news-events/nih...ein-may-be-linked-exercise-intolerance-me-cfs
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From the NIH article above:

“To better understand the role of WASF3, the team engineered mice to produce excess WASF3. They found that, similar to people with post-exertional malaise, muscles in these mice were slow to recover after exercise. The mice also showed a 50% reduction in their ability to run on a treadmill, even though their muscle strength was comparable to mice without extra WASF3.”

Apologies if this has already been highlighted in this thread but I hadn’t realised this bit. Reduced ability to exercise with no apparent reduction in strength seems really significant to me.
 
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Completely agree.

I have not lost basic strength. I can still pick up heavy objects without much trouble. Being a largish male I could probably pick up more weight than most my age.

But I have no stamina, and I pay a highly disproportionate physical price for picking up that weight, especially if I do it repeatedly.
 
Sean said:
Completely agree.

I have not lost basic strength. I can still pick up heavy objects without much trouble. Being a largish male I could probably pick up more weight than most my age.

But I have no stamina, and I pay a highly disproportionate physical price for picking up that weight, especially if I do it repeatedly.
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Ayup. There is some muscle mass loss, but it's only anything extra from the base mass, what is gain from using and growing them. When flexing, it doesn't seem any less than it was. I've lost a lot of weight in recent months so they are especially easy to see, still as well-defined as ever. The strength is definitely still there. It's just exhausted in seconds, and can be crushingly punishing if it goes over whatever limit is set there.
 
Robert 1973 said:
From the NIH article above:

“To better understand the role of WASF3, the team engineered mice to produce excess WASF3. They found that, similar to people with post-exertional malaise, muscles in these mice were slow to recover after exercise. The mice also showed a 50% reduction in their ability to run on a treadmill, even though their muscle strength was comparable to mice without extra WASF3.”

Apologies if this has already been highlighted in this thread but I hadn’t realised this bit. Reduced ability to exercise with no apparent reduction in strength seems really significant to me.
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How would they prove that it was a reduced ability to run?
 
In myself I observe low stamina, poor recovery from exertion, and an inability/very limited capacity to improve the poor stamina via training.

During a walk, I start out strong, then gradually become weak, and then symptomatic. Other people can just continue and maintain a good level of strength for much longer. They can also quickly improve this further with training, while I'm held back by PEM and the poor recovery.
 
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Low stamina was the main thing that tipped me off that something major had changed after a stomach bug that triggered my CFS ~ 20y ago. Sure I had tons of other weird symptoms all of a sudden, but this one really stood out to me.

Before my trigger I would jog / run everywhere, rather than walk, I just enjoyed the feeling of it. And, literally a few weeks after the infection, I could not run for more than 3-5 minutes without being exhausted, it was no longer enjoyable but very unpleasant instead. And no matter how much I tried I could not improve my stamina. My strength levels on the other hand had not changed. Later I did a bike test in the hospital that confirmed that my stamina was abnormally low for someone in my age group and physical parameters.

So yea the theory that something at the cellular level is impeding energy production is quite logical.

Interestingly, this reduction in stamina is not often mentioned when it comes to diagnostic criteria, which I think it should be. Even though I've read some people with CFS/ME say that they haven't noticed such stamina reduction, so maybe it is not universal and there might be subgroups.
 
borko2100 said:
Even though I've read some people with CFS/ME say that they haven't noticed such stamina reduction, so maybe it is not universal and there might be subgroups.
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My stamina has stayed around the same in the last 23 years of M.E. A viral infection and added menopause has lowered it a bit, which is a normal response for normal people too.

I definitely can not increase my activity levels or PEM sets in.
 
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