In animal models. Open access, https://www.nature.com/articles/s41467-019-13442-5 Article. https://neurosciencenews.com/exercise-replacement-15458/
"Exercise replacement" - love it! Very long and technical article so haven't been able to read all of it but it does sound potentially relevant, even if it is about fruit flies and mice. The paper looks at dysregulated TORC function, something that also pops up in ME research. Unfortunately I can't work out if it's the same sort of dysregulation - can anyone enlighten me? For example TORC features here: https://www.s4me.info/threads/an-is...me-cfs-patients-missailidis-et-al-2019.11121/ The main molecule looked at is sestrin which only seems to have had minor attention in ME. The search terms "ME/CFS sestrin" came up with a single study from 2006 (for which we don't seem to have a thread). It states "The single most influential gene was sestrin 1 (SESN1)" - so I wonder why there hasn't been more interest. Have there been failed replication studies that went unpublished or that my quick search didn't find? Or just another case of lack of funding at the time and then forgotten? Pharmacogenomics. 2006 Apr;7(3):407-19. Identifying illness parameters in fatiguing syndromes using classical projection methods. Broderick G1, Craddock RC, Whistler T, Taylor R, Klimas N, Unger ER. Red highlight mine. https://www.ncbi.nlm.nih.gov/pubmed/16610951 Tongue in cheek observation: Did they accidentally create the best mouse model for ME yet? Poor mice. ETA: from Open access, https://www.nature.com/articles/s41467-019-13442-5
Perhaps you jest, but you may well be right - Sesn triple knockout mice undergoing ramped exercise while measuring gas exchange parameters is more useful than any other model I have seen. Interesting commentary here: "Sestrin family of genes and their role in cancer-related fatigue" https://link.springer.com/article/10.1007/s00520-018-4139-8 10.1007/s00520-018-4139-8 (edit) Also: https://www.karger.com/Article/Pdf/366571 On the latter point, Sestrins inhibit MTORC1, but can activate MTORC2. I wonder what effect the following would have. https://en.wikipedia.org/wiki/NV-5138
Basic biology is very similar among mammals and anything which is the same in flies and mice is relevant to us. This is the sort of research that can lead to new ideas about ME that could be more accurate than we have. It is whether anything that helps mice would help us that is more doubtful.