Abstract The endoplasmic reticulum (ER) is an organelle responsible for the post-translational folding and modification of proteins. Under stress conditions, such as physical exercise, there is accumulation of misfolded proteins. The increased load of proteins in the ER results in ER stress, which activates the unfolded protein response (UPR). UPR is comprised of three parallel pathways, responsible for ensuring the quality of secreted proteins. Scientific studies show that resistance or endurance acute physical exercise can induce ER stress and activate the UPR pathways. On the other hand, regular moderate-intensity exercise can attenuate the responses of genes and proteins related to ER stress. However, these positive adaptations do not occur when exercise intensity and volume increase without adequate rest periods, which is observed in overtraining. The current review discusses the frontier-of-knowledge findings on the effects of different acute and chronic physical exercise protocols on skeletal muscle ER stress and its metabolic consequences. https://pubmed.ncbi.nlm.nih.gov/35152547/ This sounds like it could be relevant to postexertional malaise, or the recently reported association between the WASF protein and ME/CFS. Could an activation of the unfolded protein response also lead to a drastic reduction of excreted proteins in urine?
I don't have the first idea about the unfolded protein response but anything happening in overtraining syndrome is potentially interesting. If OTS occurs due to inadequate rest periods then it should be possible to figure out the nature of the positive adaptations that normally happen during rest. For ME you'd then want to know how these positive adaptation mechanisms can be broken so they no longer recover normally with rest.
I remember that at least one, maybe several researchers have said that ME/CFS patient's cardiopulmonary exercise tests look similar to those of overtrained athletes. Maybe PEM is caused by a defect in the body's ability to rest and recover from exertion. It makes sense that poor resting efficiency would have to be compensated by more time spent resting.
Over training is one of those phrases that everyone thinks they know what it should mean, but hardly anyone does, e.g Overtraining Syndrome: A Practical Guide* "Conclusions: OTS remains a clinical diagnosis with arbitrary definitions per the European College of Sports Science’s position statement. History and, in most situations, limited serologies are helpful. However, much remains to be learned given that most past research has been on athletes with overreaching rather than OTS." Work on OTS and the endoplasmic reticulum (ER) seems primarily to have taken place on rodents while OTS in humans is mainly concerned with elite athletes who by their very nature are not representative of the general population. Maybe there's some basic mammalian biology that is writ large in elite athletes which might provide some clue as to what some elements of ME/CFS are but it's all very speculative. *Scihub link: https://sci-hub.se/10.1177/1941738111434406
My aunt had a 23 and me DNA test years ago. My daughter had a limited DNA test for nutritional input years ago . Both reports skimmed the surface of a very complex biology and were limited , however both noted something to the effect that they shared the same muscle fibre(?) / response as endurance athletes. They re lurking on a hard drive somewhere . ETA seemed like a cruel joke at the time
More than a few elite atheletes have had Long Covid and the support groups are full of people "who were fit, runners, went the gym" etc, myself included at the modest end. Perhaps the factor that makes them biologically predisposed explains the BPS notion conflating with over-achievers. That subset may have developed impairments to the protein folding machinery which was subclinical until a second hit - say mitochondrial impairment following viral infection / transactivation. So along with the above misattributed BPS concept and remembering they're adamant that they see recoveries in some, conceivably GET could accidentally work in a subset by building in recovery times leading up to moderate exercise. Nothing to do with CBT and positive thinking and only as long as the stars aligned for that subset. If that were true and this was sufficiently upstream, then for the relevant subset who were also not incapacitated, you might be able to drive recovery via a rest/exercise regimen determined by metabolomics. --- * These references are open-access: The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1α/ATF6α complex (2011) Long-Term Exercise Protects against Cellular Stresses in Aged Mice (2018) Swimming Differentially Affects T2DM-Induced Skeletal Muscle ER Stress and Mitochondrial Dysfunction Related to MAM (2020)
Everyone has a mix of fast twitch and slow twitch muscle fibres - for those who are intent on athletic performance their particular mix will define which type of activity they may (depending on many other variables) excel at. The notion that athletes are especially prone to ME/CFS has been around since at least the late 1980s but there seems to be no confirming data, and certainly nothing that would separate sprinters from triathletes.
My unevidenced hypothesis re athletes is simply that they are likely to push themselves back into training too soon after an infection, and that people who are pushed to get back to work, child care etc instead of being able to convalesce sufficiently for long enough are the ones more likely to end up with long term symptoms including PEM.
