Old Muscles in New Bodies - Are the Muscles in ME/CFS Aging Rapidly?

[Cort]

Fascinating review. We forget how much evidence there is for muscle dysfunction in ME/cFS. Most of the studies are, as I remember, small but the results are interesting.

Several other studies involving telomere's suggest aging is happening more rapidly in ME/CFS. Plus it appears from metabolomic studies that men with ME/cFS are catabolizing their muscles to provide substrates for energy production. Plus some studies showing that the motor cortex in the brain may not be activating muscle properly.

Now this on muscles showing

1. high rates of oxidative stress
2. issues with muscle contraction
3. problems with glucose uptake
4. problems with mitochondrial activity
5. problems with energy production

They do get into some dangerous group with "appropriate training program" and some CBT stuff but overall it appears highly physiological. They even get into potential NAD and NADPH issues, which if memory serves, is something the Metabolic Trap hypothesis suggests.

It the first full blown review of muscle metabolism that I can remember.

Eur J Transl Myol. 2018 Sep 7;28(3):7688. doi: 10.4081/ejtm.2018.7688. eCollection 2018 Jul 10.
Old muscle in young body: an aphorism describing the Chronic Fatigue Syndrome.
Pietrangelo T1,2, Fulle S1,2, Coscia F3,4, Gigliotti PV3,4, Fanò-Illic G1,2,5,6.
Author information

Abstract
The chronic fatigue syndrome (CFS) otherwise known as myalgic encephalomyelitis (ME), is a debilitating syndrome whose identification is very complex due to lack of precise diagnostic criteria. This pathology begins with limitations in duration and intensity of exercise and rapid onset of pain during physical activity. Its etiology is unknown, and symptoms are not limited to the muscles. Epidemiology is rather difficult to delimit, even if it affects mainly young (20-40 years), female subjects. The results of muscular research show some peculiarities that can justify what has been observed in vivo. In particular,

1. presence of oxidative damage of lipid component of biological membranes and DNA not compensated by the increase of the scavenger activity;
2. Excitation-Contraction (E-C) alteration with modification of Ca2+ transport;
3. passage from slow to fast fiber phenotype;
4. inability to increase glucose uptake;
5. presence of mitochondrial dysfunction; and
6. genes expressed differentially (particularly those involved in energy production).

The skeletal muscles of CFS / ME patients show a significant alteration of the oxidative balance due to mitochondrial alteration and of the fiber phenotype composition as shown in sarcopenic muscles of the elderly. Vice versa, the muscle catabolism does not appear to be involved in the onset of this syndrome.

The data support the hypothesis that patients with CFS are subjected to some of the problems typical for muscle aging, which is probably related to disorders of muscle protein synthesis and biogenesis of mitochondria.

Patients with CFS can benefit from an appropriate training program because no evidence suggests that physical exercise worsens symptoms. Type, intensity and duration of any physical activity that activates muscle contraction (including Electrical Stimulation) require further investigation even if it is known that non-exhaustive physical activity decreases painful symptomatology.

 

[Wishful]

I don't know how to contact the group, but if someone can, please tell them that not all ME/CFS victims have skeletal muscle problems. Researching a secondary effect could be useful, but it will probably be more likely to reach proper conclusions if they know that it's a secondary effect rather than a primary effect.

 

[Cort]

I'll have a blog coming up soon on a new method to increase blood flows and get the muscles working a bit without ...gasp...exercise!

I think it may actually work.

 

[Cort]

I don't know how to contact the group, but if someone can, please tell them that not all ME/CFS victims have skeletal muscle problems. Researching a secondary effect could be useful, but it will probably be more likely to reach proper conclusions if they know that it's a secondary effect rather than a primary effect.

It's funny. I just heard of an ME/CFS patient of Dr. Bateman who can exercise to his hearts delight but cannot tolerate mental exertion at all. I wonder if problems with energy production or blood flows are found in different areas in different patients. I wouldn't be surprised at all.

It would be nice to nail down muscle problems in that subset of patients which do have them...In fact, it would be great! If the new ME/CFS Research Center rat Harvard run by Ron Tompkins and created by Ron Davis gets the funding it needs it could go a long way to explaining what the heck is going on with the muscles in ME/CFS. Ron Tompkins wants to do exhaustive muscle biopsy studies in ME/CFS.

 

[Wishful]

I just hate seeing part of the limited resources going to secondary effects when it could be used to find the primary cause. Fix the primary cause, and all the secondary effects are no longer a problem. If funding was unlimited, then I'd agree that the research was worthwhile, since it might apply to other disorders.

 

[Cort]

I just hate seeing part of the limited resources going to secondary effects when it could be used to find the primary cause. Fix the primary cause, and all the secondary effects are no longer a problem. If funding was unlimited, then I'd agree that the research was worthwhile, since it might apply to other disorders.

I wonder if producing definitive evidence that muscle problems are present would result in a push to find the ultimate cause - which I assume is some sort of problem with energy production....(???)

 

[HowToEscape?]

I just hate seeing part of the limited resources going to secondary effects when it could be used to find the primary cause. Fix the primary cause, and all the secondary effects are no longer a problem. If funding was unlimited, then I'd agree that the research was worthwhile, since it might apply to other disorders.

Am not a scientist, so I must comment in a tangential way.

Many times one doesn't have the option of building from the foundation up. In a non-physical structure, you may have to install any pieces you can get into where they appear to belong, and then later move the pieces (e.g "this cell function is relevant, but not to the other parts at first believed"), modify pieces (x is actually broken, but not the way we first thought), remove pieces (x is really a distraction) or change the building (z previous assumption in wide use was not correct).

Why cant you do everything in neat logical order (pour the foundation, add beams, etc etc)? That's not an option; we don't know where all the foundation needs to go, we don't know very well what's going atop it, we don't have enough concrete or cement mixers, etc, we don't know if this will be an office or an apartment tower, but it has to be done before, say, the Mongols arrive. So we start prefabbing HVAC, window units, pipes and wires at the site even though it would be too soon were this a physical building. The analogy breaks here because it's not a physical building, but you get the idea.

So you need people who can deal with informational semi-chaos, partial and defective knowledge and keep working. This isn't as rare as it sounds, this is just dealing with Nature and complex man-made systems.

 

[Cort]

Am not a scientist, so I must comment in a tangential way.

Many times one doesn't have the option of building from the foundation up. In a non-physical structure, you may have to install any pieces you can get into where they appear to belong, and then later move the pieces (e.g "this cell function is relevant, but not to the other parts at first believed"), modify pieces (x is actually broken, but not the way we first thought), remove pieces (x is really a distraction) or change the building (z previous assumption in wide use was not correct).

Why cant you do everything in neat logical order (pour the foundation, add beams, etc etc)? That's not an option; we don't know where all the foundation needs to go, we don't know very well what's going atop it, we don't have enough concrete or cement mixers, etc, we don't know if this will be an office or an apartment tower, but it has to be done before, say, the Mongols arrive. So we start prefabbing HVAC, window units, pipes and wires at the site even though it would be too soon were this a physical building. The analogy breaks here because it's not a physical building, but you get the idea.

So you need people who can deal with informational semi-chaos, partial and defective knowledge and keep working. This isn't as rare as it sounds, this is just dealing with Nature and complex man-made systems.

Ha...Yes, it would be nice if we could actually do this in a nice logical order but I guess it is inherently messy isn't it and with all these hypotheses swirling it's particularly messy in ME/CFS.

 

[Wishful]

I wonder if producing definitive evidence that muscle problems are present would result in a push to find the ultimate cause - which I assume is some sort of problem with energy production....(???)

Studying muscle problems in victims who do have them could indeed lead to figuring out what is causing them, so I'm not saying that it's useless research. However, my experience (and that of others posting here) is that some ME victims don't seem to have muscle problems, which makes it a secondary problem, and thus less likely to lead to the ultimate answer than research done in other areas, such as the brain (where I believe the problem lies). I am not an expert, and don't think I'm qualified to decide where research funding goes, but my observations of my ME say that the problem is in the brain, not the rest of the body.

Howtoescape's point is valid: we don't yet know for sure where to look for the answer. However, since there are limited resources, we can make a best guess based on the latest evidence. My initial post was in the hope that researchers would factor in the evidence that not all ME victims have muscle problems or hindered metabolic limits. Some might not be aware of this. ME did not reduce my muscular strength or endurance. It does reduce my mental energy.

 

[Hip]

I don't know how to contact the group, but if someone can, please tell them that not all ME/CFS victims have skeletal muscle problems.

If PEM begins in the muscles, due perhaps to some blockages in the mitochondria of those muscles, then most ME/CFS patients would have skeletal muscle problems.

And nearly all the studies on ME/CFS muscle biopsies found enterovirus or Epstein-Barr virus infections in those muscles.

 

[Wishful]

I'd like to know what percentage of ME victims don't have muscle problems. I still have this thought that it could be related to the genetic differences between cerebral mitochondria and the mitochondria elsewhere in the body. If a mito genetic defect is involved, there could be a group where the defect is only in the brain.

I wonder what percentage of victims in those muscle biopsy studies were part of the 'no-muscle-problem' subgroup. Perhaps those studies selected volunteers based on their muscle problems, or even for characteristics specific to virally-infected muscles.

I still feel that the existence of this subgroup without muscle problems means that muscle problems are a secondary problem, even if it is a very common one. That seems more likely than a rare secondary effect that blocks the muscle symptoms while allowing the cerebral symptoms.

 

[Hip]

I still feel that the existence of this subgroup without muscle problems means that muscle problems are a secondary problem, even if it is a very common one.

One idea I had is that if you get PEM from mental exertion, but not much PEM from physical exertion, perhaps that may simply reflect the organs that are virally infected.

If a patient has more mental than physical PEM, perhaps they don't have much infection in the skeletal muscles, and more infection in the brain.

In my case, my ME/CFS started after a viral brain infection, so the virus definitely got into my brain. And I definitely suffer much more from mental PEM than physical PEM.

 

[Wishful]

I do get PEM from physical exertion, except when I take my marvelously effective PEM-blocker. I forgot to take it on time a few days ago and was reminded just how bad my physically-induced PEM makes me feel. My cerebrally-induced PEM is less common because I avoid those triggers more effectively. I generally go about 3 weeks without talking to another human; I'm physically active most days.

I think my ME was initially triggered by a tetanus booster. That's non-viral, but for your theory would probably count as muscular. You haven't convinced me of your viral/organ theory.

 

[Hip]

You haven't convinced me of your viral/organ theory.

I have not convinced myself either! It would need supportive evidence from viral testing to convinced me; it's just an idea I had.

 

[unicorn7]

Maybe it’s all one disease with different subsets, but maybe it’s different diseases all together.

Research on muscle tissue would be my number one interest, because my problem is primarily muscle fatigue/weakness/pain.

Taking muscle biopsies is pretty easy compared to research on the brain.

 

[Hip]

Taking muscle biopsies is pretty easy compared to research on the brain.

The ME/CFS research from the UK in the 1980s and 1990s used to take muscle biopsies and test this tissue for enteroviruses. But muscle biopsies are painful and leave a scar. That's why Dr Chia pioneered the stomach tissue biopsy for enterovirus testing, as this is not painful and easier to do.

 

[Wishful]

I think one core dysfunction with multiple effects is much more likely than multiple core dysfunctions that create such similar symptoms. We don't all have PEM with a 24-hr delay, but we all (the definition of ME) have PEM, which I'm guessing fits into a few general subgroups. While we don't all suffer the muscle problems, those that do seem fairly similar.

If muscle problems are your primary symptom, I can see why you'd want to focus on that. However, treatment for that wouldn't solve the core problem, so you'd still have other ME issues that would probably become more noticeable. Solving the core problem would solve the muscle problems and the other issues. That's why I think that resources should go to the core problem first, rather than being divided up among secondary problems.

 

[Hip]

Solving the core problem would solve the muscle problems and the other issues.

I agree that solving the core issue is important, but as far as I am aware, I don't think that globally speaking, there is a fixed amount of ME/CFS funding that gets divided up among the world's ME/CFS researchers that apply for grants to do their studies.

In this example, the study was performed in Italy by researchers from various departments including sports science departments. But I don't think the money they used would have been taken out of Italy's ME/CFS fund pot (I don't think there is such a pot), thereby denying other ME/CFS researchers in Italy funding.

On the other hand, if you take an ME/CFS organization like say the OMF, they do have a fixed amount of funding each year, so in these cases if they use their money to study one area, that may prevent them from studying another area.

 

[serusaert]

this is fascinating. i have lots of muscle loss. there is more research out there on ATP and muscle fast fiber conversion - i found one that used a 20 hz current to induce the conversion: https://www.fasebj.org/doi/abs/10.1096/fasebj.28.1_supplement.1164.11

and they saw that ATP was definitely involved and offer some possible investigations:

ATP release plays a key role in this process, being able to activate, in the absence of electrical stimulation, most of the transcriptional changes observed after 20 Hz stimulation. In fibers depolarized to using external K+, we documented calcium signals and transcriptional changes similar to those observed after 20 Hz stimulation. Addition of 100-500 µM external ATP induced muscle fiber depolarization and that transcriptional changes observed after stimulation of fibers with 30 µM external ATP, were abolished by 25 µM nifedipine, a Cav1.1 inhibitor. These two events were completely inhibited by the IP3R blocker Xestospongin B, suggesting that IP3-dependent events are triggered at these membrane depolarization values.​

so, maybe there is a way to address the muscle wasting symptom?

 

[Sing]

Muscle aching, contraction-stiffness, and weakness have been ongoing problems for me throughout the over 20 years of this. I handle it by quite a lot of daily stretching as well as using either a hard wooden roller or foam roller that I lie on, move around on to help release the most contracted muscles. This seems to letting in blood, oxygen, clearing out the excess lactic acid and waste products. I have to mechanically help my body, in other words, to do what it isn’t doing anymore by itself. A potential nightmare for me would be a scenario where I could no longer stretch at least, because my muscles and fascia bind up, block circulation, pull on and compress joints and vertebrae, etc. It would be an increasing torture. A “muscle relaxing” pill could not possibly do for me what mechanical work does—either through my own stretching and deep massage via rollers or through deep massage work given me. Can’t afford a $100 massage every day and so have to try to work out the knots and contractions myself.

One of the ironic things about aging and progressive weakness is that my muscles can’t put up as much of a fight “against me” as they did earlier. Years ago, I had to spend a total of 1 ½ hours a day of concentrated stretching and self massage, but now, approaching age 70, it is half of that. Muscle wasting seems to have this silver lining of making them less able to fight against me.

I don’t know what is going on technically, but Dr. David Systrom’s exercise testing showed reduced oxygen delivery or uptake in the muscles. This accompanied hypotensive problems and PEM in his study of a group of ME/CFS patients. I have a serious level of OI and regular PEM, so would fit that particular profile of dysfunction.