John Hemming's Web Log

I am using this page to collate research papers looking at what disease are probably caused by differentation failure. It is at a really early stage at the moment. It has a useful collection of links, but no real analysis. Atherosclerosis Mummies reveal that clogged arteries plagued the ancient world Looks like it is not a modern diet The Role and Research Progress of Inhibitor of Differentiation 1 in Atherosclerosis Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment Why do statins work? I think it is clear that statins work. What they do is to prevent citrate being converted into Cholesterol. This has two effects. A) Less Cholestoral, B) more citrate for other things. Clearly that would help with differentiation and would be a mechanistic route whereby Statins work. Osteoporosis Chromatin remodeling due to degradation of citrate carrier impairs osteogenesis of aged mesenchymal stem cells This paper bl

I think it is worth bringing together some of the research on Acetyl-CoA and what it can affect when it is not being used to generate energy for cells (ATP). Its worth reading my other blog pages which are associated with this: Gompertz, Interleukin-10 and the gradual deterioration of health which also looks at Citrate Insomnia, Health and Dietary Supplements (Particularly Vitamin D (D3) and Melatonin) I have not reviewed this for accuracy recently, but it is still worth looking at. So, to recap ... Acetyl co Enzyme A is created in the cytosol (the area of the cell which is outside the mitochondria or nucleus) from Citrate. Citrate can come out of the mitochondria via the citrate carrier, this will not be the only source of cytosolic citrate even if it is the main source Acetyl-CoA A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation is a paper that looks at some of the things Acetyl-CoA does in the cell outside the mitochondria.

This blog post is another work in progress. In it I intend to consider the research on HIF and what the possible models are that lead from varying partial pressures of Oxygen in breathed gas (and the time of exposure) and the various possible outcomes (HIF, NRF2 and NF-κB). I shall aim to write this for people who have some scientific knowledge with links to the research. If you are reading this and would like me to expand on an explanation please comment. Disclaimer: This is not medical advice. Before you decide to do anything get advice from your doctors. Different people are affected in different ways and expert advice on your own personal circumstances is needed. Glucose and Oxygen Cells in animals generate energy as a molecule called ATP (Adenosine Tri Phosphate). This can be done in a number of ways. Generally the process starts with Glucose (ignoring for now when the body is using Ketones). If there is enough Oxygen then a process called Oxidative phosphorylation oc

Part of my hypothesis that there is a feedback mechanism between the failure of Stem Cells to Differentiate and the failure of more Stem cells to differentiate is that failed stem cells (senescent cells) issue a molecule as part of SASP into the blood which then affects other Stem Cells. I think it is most likely that this molecule is Interleukin-10. (In fact having done the research I think it is reasonably certain) I picked it because it is both an inhibitor of NF-κB and also part of SASP My plan for this blog post is to hunt down papers on Interleukin-10 and see whether they support this hypothesis or not. That will, of course, be a work in progress. The portuguese research in red is particularly interesting Inhibitors of NF-κB signaling: 785 and counting what is nice about this paper is that it has an appendix with 785 inhibitors of NF-κB. Wikipedia on SASP this tells us what is in SASP and links to the research on this. Research that supports the Hypothesis Study on rel

The Gompertz–Makeham law of mortality is a formula used to predict mortality. The Makeham element is the external part of this such as disease or accidents. The Gompertz part relates to the gradual deterioration of health of an entity. Not all animals follow the Gompertz formula, but Human Beings do. It is an exponential increase in death rates with age. My view is that this implies that at the core of the issue of the gradual deterioration of health there is some relatively straight forward feedback loop which drives this. I have, therefore been studying the research to look for a hypothesis that has a potentially exponentially reinforcing feedback loop - which would start very small. I have a good candidate for this now. I will later edit this blog post to put all the references in, but I am now going to write the basic post and come back to that. Many diseases have at the core of them the failure of Stem Cells to properly differentiate. For one disease last year (Osteoporo

As part of my work on sleep and health I have been researching why cells deteriorate. There is a lot of good research out there, but I think now it is possible to see a reinforcing vicious circle that is at the core of many deteriorations in health. I think what happens is that an increase in inflammation causes a reduction in NF-κb which causes a reduction in SLC25A1 which reduces the number of citrate carriers which causes the differentiation of stem cells to fail more often and those turn in to senescent cells which then increases inflammation. Obviously those would not be all senescent cells, but I think it would be a substantial proportion. Noting that the Naked Mole Rats don't really have that many it is consistent. Please note that it is the level of NF-κb in the Stem Cells which will be key in setting the state of the Citrate Carrier. I have done a video that looks quickly at this and how people can try to improve their cellular health. Inflammation ꜛ ->NF-κb ꜜ