The Rhyothemis princeps Brain Externalization Project

Returning to my quest to understand the mechanisms of chronic nausea and vomiting, I revisited mirtazapine for cats. The main reason cats are prescribed Mirtz is for nausea and vomiting (NV) from azotemia or uremia due to chronic kidney disease, which older cats are prone to suffer. So which uremic toxins are implicated in NV?  Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA).  ~ SDMA has been found to be lower in women with ME/CFS: https://www.frontiersin.org/articles/10.3389/fmed.2021.642710/full hmmm ... so I guess this is not a cause of nausea in ME/CFS ... more on related metabolic pathways in ME/CFS: http://followmeindenmark.blogspot.com/2019/03/polyamines-5-methylthioadenosine-and.html  ~ database entry on SDMA: https://hmdb.ca/metabolites/HMDB0003334  "Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. This seems to be mediated by the direct binding or inhibition by ur...

 I don't even have time today to post links to references and  hope I can find them again at some point in future ... {update 2021-07-18 - I'm working on it} A commenter on YT that I had previously discussed how methionine restriction can actually cause an increase in homocysteine levels asked me what I thought about the apparent paradox - since methionine restriction (MR) lengthens lifespan, but high homocysteine / hyperhomocysteinemia (HHcy) should cause an increase in mortality from CVD (and other things). In lab animals HHcy is induced by feeding excess met and restricting B12, folate and B6. But low met decreases CBS activity, which can also cause HHcy. Chronic HHcy can cause hypermethylation of the CBS gene, reducing its expression. I'm guessing that's why clinical trials to lower Hcy with vitamin B6 etc. don't necessarily result in improvement in cardiovascular health - CBS is still not working and H2S signalling is still impaired. Maybe not the case, though,...

  A brief review on how statins could be used to treat immune thrombocytopenia (ITP), an autoimmune disease: Nazy and Cuker (2018) - Statins for high cholesterol … and for low platelets? - https://doi.org/10.1182/blood-2018-01-824888 "Megakaryocytes in ITP patients show impaired maturation and signs of degradation due to defects in the megakaryocytes and their environment. 7   Among the cells in the BM [bone marrow] niche implicated in supporting megakaryopoiesis and thrombopoiesis are the BM EPCs [endothelial progenitor cells], ... Treatments that induce platelet production by enhancing the BM microenvironment could be beneficial for corticosteroid-resistant ITP. Atorvastatin is a widely used drug for the treatment of primary hypercholesterolemia and mixed dyslipidemia by inhibiting 3-hydroxy-3methyl-glutaryl-coenzyme A reductase. Among its activities, it is known to improve the mobilization and function of EPCs. Recently, Shi et al showed the effectiveness of atorv...

Two mind-blowing articles on the effects of geomagnetic field fluctuations on human health, published in highly ranked peer-reviewed journals. Otsuka et al. (2019) Anti-aging effects of long-term space missions, estimated by heart rate variability  https://www.nature.com/articles/s41598-019-45387-6 "Exposure to variable magnetic fields in space resulted in an increase in several HRV endpoints, suggesting that aging may also be slowed down in astronauts in space, as it was for Caenorhabditis elegans 18 . By contrast, our previous 1998–2000 studies (during solar cycle 23) in a subarctic area indicated that magnetic storms, which involved larger magnetic disturbances than those observed during ISS01 and ISS02, suppressed HRV indices in 19 clinically healthy subjects 24 . The decrease in HRV was statistically validated for TF (−18.6%, P = 0.00009), primarily contributed to by VLF (−21.9%, P < 0.000001) in conjunction with ULF (−15.5%, P = 0.00865) and LF (−14.2%, P = 0.001...

Modern Healthspan released a video on an article that reports that shikimic acid reduced markers of  UV light induced cellular senescence in cultured dermal fibroblasts, increased SIRT1 activity and restored proteostasis . As MH suggests in the video, these findings could have much broader implications. Video: https://youtu.be/m_qaZSsFiT8 Research article:  Martinez-Gutierrez et al. (2021) https://www.aging-us.com/article/203010/text "SA reverted misfolded protein accumulation upon senescence, an effect that was abrogated by EX-527. Consistently, SA induced an increase in the levels of the chaperone BiP, resulting in a downregulation of unfolded protein response (UPR) signaling and UPR-dependent autophagy, avoiding their abnormal hyperactivation during senescence. SA did not directly activate SIRT1 in vitro, suggesting that SIRT1 is a downstream effector of SA signaling specifically in the response to cellular senescence. Our study not only uncovers a shikimic acid/SIRT1 signa...

Yesterday Lifespan.io reported on a finding by Wen et al. (2021) that vibration at 90 Hz reduced cellular senescence in bone marrow mesenchymal stem cells; from the news article's conclusion: https://www.lifespan.io/news/vibration-reduces-cellular-senescence-in-the-bones-of-rats/ "Further, while maintaining bone density is crucial to extending healthspan, vibration does not seem to be a great candidate as an anti-aging therapy. One of the greatest advantages of a longevity-based approach is its application to all the tissues in the body, and while the authors of this study did not investigate the effect of vibration on other organs, it seems logical that these effects would apply only to bone tissue."  Original research article: https://www.aging-us.com/article/202907/text  However - https://pubmed.ncbi.nlm.nih.gov/16364518/ “Longstanding evidence that bone formation and resorption are required for the development of haemopoietic marrow strongly suggests that ost...

 Someone on a forum asked about carnosine ... Carnosine is interesting since it can quench reactive carbonyl species such as acrolein. Acrolein can cause the formation of methemoglobin in red blood cells, which reduces oxygen delivery and can cause fatigue. Later stage PD patients have elevated levels of methemoglobin in RBCs. RBCs actually have a dopamine transporter and it may function to clear excess dopamine (maybe, not really known at this point). Oxidized dopamine can also interact with hemoglobin to form methemoglobin. Carnosine was found to reduce acrolein-induced methemoglobin in the following paper - which is unfortunately paywalled. The abstract says the carnosine had no effect on metHb formed by dopamine, but in the article it shows that the carnosine had an overall effect of greatly lowering the amount of metHb in the RBCs. The same group also put out a meeting abstract (so not peer -reviewed) that reported a lowering of the metHb caused by dopamine with spermidine. ...