John Hemming's Web Log

Role of autophagy in aging: The good, the bad, and the ugly is a really good review into the function of autophagy (eating yourself) which is how cells tidy themselves up by getting rid of dysfunctional mitochondria and creating new ones. Autophagy is a good thing because it makes cells work better. That almost certainly ups the Acetyl-CoA levels in the nucleus which readers of this blog will know is a *Good Thing . [Incidentally if you have the time its worth reading all of the review] I will extract part of the review: Unfortunately, the protection afforded by autophagy is progressively erased with age. For instance, Atg5, Atg7, and Beclin 1 are down-regulated in the normal aging brain, whereas, in osteoarthritis, the levels of ULK1, Beclin 1, and LC3 fall (Rubinsztein et al., 2011). In hepatocytes of aged rats, alongside the increase in cytosolic Hsc70, and coordinate with decreased binding and lysosomal uptake of cargo, there is a significant rise in degradation and hence red...

People who read my blog will be aware that I have for some time argued that most (if not all) diseases of aging are caused by cells not being able to produce enough of the right proteins. What happens is that certain genes stop functioning because of a metabolic imbalance. I was, however, mystified as to why it was always particular genes that stopped working. Recently, however, there have been three papers produced: Aging is associated with a systemic length-associated transcriptome imbalance Age- or lifestyle-induced accumulation of genotoxicity is associated with a generalized shutdown of long gene transcription and Gene Size Matters: An Analysis of Gene Length in the Human Genome From these it is obvious to see that the genes that stop working are the longer ones. To me it is therefore obvious that if there is a shortage of nuclear Acetyl-CoA then it would mean that the probability of longer Genes being transcribed would be reduced to a greater extent than shorter ones. ...

The last few days have been quite interesting in the supplements space. We had the FDA banning NMN and the reports that NR may encourage some forms of cancer. FDA says ingredient studied as drug—β-NMN—is excluded from supplements is one of a number of stories which explain how the FDA have concluded that NMN is actually excluded. It wasn't really so much a decision of the FDA actually to ban NMN as a supplement as a reinterpretation of the regulations that found that NMN should not be allowed as a dietary supplement. At the same time we have had Study: Popular dietary supplement causes cancer risk, brain metastasis which is based upon A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism . The first one was not really something intentional, and may be changed by discussion and/or legal action. It also only has effect in the USA. The second one, however, is more serious and i...

I have been working on improving the health of the cells in my body, with some success, for a while now. This year, however, I have decided to monitor the situation with what are essentially weekly blood tests. I started out the year with blood tests every 4 weeks, but in May I moved to weekly tests. Apart from a short period when on holiday I have had at least one blood test each week since May 5th 2022. I have found this a particularly useful process, but in doing this I have learnt some things that are I think important for others to know. Hence I thought I would write this blog post. I have used a number of different Laboratories. Most Laboratories offer a form of general health screen which covers basic biochemistry and the health of various organs such as the kidneys, liver and heart. The selection of tests often varies in detail, but certain tests such a Creatinine and Haemoglobin tend always to be done. I was concerned, however, that I did not think some of the result...

On Wednesday 13th July there was a hearing in my case against Sonia Poulton. There have been a lot of technical hearings and it has been back and forth with costs going each way. So far, everyone has made a net loss. For example, as MHN points out , there have been a number of mixed costs orders. The difficulty is Sonia only reports the ones that go her way, but fails to mention things that do not support her account. Indeed, that is how this started. My issue with her so called, "reporting" is that she only reports one side of the argument. This then results in putting my family at risk and causing distress for my family and myself. In 2015, Esther Baker accused me and several others of rape. But since then, things have moved on - her allegations have been found, "untrue" in the High Court and she has been restrained for life from repeating them. The allegations are now deemed so lacking in credibility they have been removed from my ECRB - meaning I could apply ...

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...

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 TCA (Tricarboxylic Acid) being converted into Cholesterol. This has two effects. A) Less Cholestoral, B) more TCA 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 ...

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...

Note this photo: What you have is three images at different levels of magnification of some hair cells. These are hair cells which have not produced hair for some time. I have been doing some experimentation. As a result of my experimentation I have found a protocol which I believe makes cells which were senescent start to function. I think there are some side effects with this protocol. Hence if anyone wishes to try it I am happy to give details in confidence. However, they have to have the support of a healthcare professional as well as be willing to do blood tests at a reasonable frequency. In this photo you will see cells which were on a bald patch starting to produce hair. The hair is finer than other hairs although some are white and some are pigmented. This also works for other cell types which start functioning properly. Further Explanation 2/7/2022 A question was asked as a comment and I have modified the post to try an explain a bit more. If people want mo...

Please see Interleukin-10 Review of Research

Please see Gompertz, Interleukin-10 and the gradual deterioration of health .

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...

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 ...