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The Genome Rides on a Citric Acid Bicycle

I recently attended the British Society for Research on Aging annual scientific conference which was held this year in Birmingham. There were a number of interesting talks and about 45 posters were presented. This included one from me. The details in that poster can be seen on this link . One benefit of conferences which are in person is that conversations can continue after the presentations and issues can be refined through discussions either in the corridors or over food. The area I am particularly interested in is how the links between mitochondrial efficiency and the genome operate. I managed to refine my understanding of two of the aspects here. The Citric Acid Bicycle The first area I managed to refine is to understand the mechanisms that underpin citrate efflux from the mitochondria. To understand this fully it is perhaps best to consider the operation of two citric acid cycles. In fact realistically it is a Citric Acid Bicycle - as the two cycles are linked. Th...

Trudiagnostic change PACE leaderboard algorithm - was in position 40, now position 44 - does it matter?

Trudiagnostic have changed the way they handle the Rejuvenation Olympics Leaderboard algorithm. The result of this initially was that I was globally no 40 and have now dropped to 44. Trudiagnostic are a US company that get samples of blood and they look at the DNA to see which parts of the DNA have methyl groups (CH3) attached to them. These modifications to DNA are called methylation markers. DunedinPACE is an algorithm which uses DNA methylation markers in white blood cells to work out how quickly or slowly someone is aging. I had three results on this. The odd thing about the results was that whilst my epigenetic age calculated from the same methylation markers was going down, the speed at which I was aging was going up. I find this somewhat counterintuitive. It is, however, I think relevant that in a global contest my approach on biochemistry which is quite different to many other people's does seem to keep up with others working in the same area. To that extent it...

Why are babies born young?

Why are babies born young? This sounds like an odd question. People would say "of course babies are born young". However, this goes to the core of the question of human (or animal) development. Why is it that as time passes people develop initially through puberty and then for women through menopause and more generally getting diseases such as sarcopenia, osteoporosis, diabetes and cancer, but most of the time babies start showing no signs of this. Lots of research into this has happened over the years and now I think it is clear why this is. It raises some interesting questions. Biological youth is about how well a cell functions. Cells that are old in a biological sense don't work that well. One of the ways in which cells stop working is they fail to produce the full range of proteins. Generally the proteins that are produced from longer genes stop being produced. The reason for this relates to how the Genes work (the Genome). Because the genome is not gettin...

If you are thinking of starting to take Rapamycin for its general health benefits start by photographing your nails

Now this might seem an odd suggestion. However, if you are starting Rapamycin I think you should first photograph your nails. That is because Rapamycin affects the growth of many people's fingernails and you may wish to titrate your usage of Rapamycin by how you see the effects on your nails. Rapamycin is known as an mTOR inhibitor. mTOR is a kinase in each cell that passes signals around relating to cell growth. If mTOR is activated then there is plenty of nutrients and so the cell can get on with building things. If mTOR is inactive it means nutrients are scarce and the cell needs to start recycling things to make them more efficient. Hence inhibiting mTOR (through the use of Rapamycin or fasting) can get the cell to start the process of autophagy The particular aspect of autophagy that is very useful is mitophagy where the cell starts recycling mitochondria. The less efficient mitochondria have a lower MMP (Mitochondrial Membrane Potential) {normally} and the cell auto...

Space Medicine Expert and Oxford Visiting Professor in Ageing Research join Ex-MPs $101 Million XPrize Biohacking team developing “Royal Jelly” for human beings.

Space Medicine Expert Dr Rawan Al Shammari has joined the “Biohacking to improve everyone’s health” XPrize healthspan team headed up by John Hemming who was previously a Member of Parliament, in the UK. Oxford Visiting Professor Dr Richard Siow has also joined the team as the academic advisor. XPrize healthspan is a USD $ 101 Million contest organised by the XPrize foundation as a global contest to see which teams can improve human health by the equivalent of 10-20 years in the three areas of cognition, frailty and immune system. John Hemming is an erstwhile Liberal Democrat Member of Parliament who has successfully run a number of businesses and who has created the “Biohacking to improve everyone’s health” team as part of the XPrize. Dr Rawan Al Shammari is a medical doctor who specialises in Space Medicine. She has been appointed as the medical advisor to the team. Dr Siow has also joined the team as the academic advisor. The team is working to develop a protocol which improve...

Epigenetic Age Changes - what do they mean? Has my biological age really gone from 63 to 37?

The concept of an Epigenetic Clock has been around for some time. The idea is that there are markers on DNA from which it is possible to work out someone's biological age. The idea of "biological age" is that it is in essence a measurement of how healthy someone is. People with the same chronological age, but different biological ages differ in their health status. My own personal view is that in fact the overall health of an individual is a driven by the status of all of the cells. Hence one person can have a particularly unhealthy pancreas whilst another person has a particularly unhealthy kidney. However, the idea of a biological age is useful to the extent that it is an easy concept to understand even if realistically it is an oversimplification. There is then the idea that if you can reduce someone's biological age that means improving their health status. This is a good approach in the sense that we ideally would be trying to ensure people are so health...

Neural Networks Introduction

As readers may know I have been helped in my court cases over the past few years by Samuel Collingwood Smith. As well as being a law graduate and former councillor, Sam is also a software developer and recently he has begun two article series on artificial intelligence. One focuses on neural networks, one more on the tensor mathematics used in modern AI and neural networks. These are intended to be simple, step-by-step introductions for those new to both topics. Introduction to Neural Networks Introduction to Tensors in Neural Networks

UK Autophagy Network and the importance of autophagy for health (Healthspan and Longevity)

On 19-20 June 2023 I attended the conference of the UK Autophagy network. They have a website for the conference here and https://twitter.com/autophagyuk is their twitter account. This was a really interesting conference. My degree is in Physics specialising in Theoretical, Atomic and Nuclear physics. However, I have spent a lot of time reading up on molecular biology in the last few years. This is mainly to improve the health of my own cells which I believe (with some evidence) will improve my health as an individual. I have ended up as a biohacker, which is someone who uses cutting edge science to improve their own health making their own decisions. I am pleased that the UK Autophagy network decided they would allow me as a biohacker - they described me as an Independent Student - to attend their conference. Autophagy comes from the greek words which imply "eating oneself". It is a key part of cellular metabolism. In many ways it is obvious why Autophagy would b...

HDAC inhibitors and Gene Expression (The Sirtuins are not longevity genes) - Resveratrol etc

I have been reading up on the issues around acetylation of the histone and I have some ideas as to the interplay between acetylation and deacetylation. There are two steps in creating proteins. The first is called "transcription". This is where a complex called RNA Polymerase II (RNA Pol II or RNAPII) travels down the gene creating messenger RNA (mRNA) as essentially a local copy. The second is "translation" where proteins get created from the mRNA. Although I think there are important metabolic constraints on protein creation in this post I am going to concentrate on "transcription". One of the key things about Transcription is that for RNA Pol II to get at the genes to copy from them the genes need to be opened up. The opening up process is where an acetyl group (think vinegar without the hydrogen ion or oxygen which would attract the hydrogen) is added to the histone which holds the DNA. This causes it to open up as a result of the electric char...

NAD (Nicotinamide adenine dinucleotide) and aging - does differential expression of KYNU and KMO genes reduce NAD levels.

Nicotinamide adenine dinucleotide (NAD) is a chemical found in cells which is at the centre of many metabolic processes. It has been noted by many people that NAD levels go down as people get older. I won't go into any of the details of the impact of this as it can be read in many other places. This is just one of many articles about this. I am not citing it particularly, but it is one I found in a few second searching on the net. Recently Michael Lustgarten produced a video: I have linked to the video to a point at which the alternative route of producing NAD from Tryptophan is highlighted Most of the discussions about NAD relate to how it is produced from different versions of vitamin B3 which includes NMN and NR. Indeed there have been many debates about what is the best way to increase NAD+. The video got me thinking. The video highlights how there is an increase in the metabolite (3-hydroxy-l-kynurenine) produced by Kynurenine 3-monooxygenase (which is produced ...

Homes for Lambeth Scandal Reveals Labour Failures and Concerns About Executive Paul Simpson

I came across this story written by a friend about a national scandal that I consider raises issues of concern about the provision of housing for vulnerable groups and Labour failures. According to a report by independent peer Lord Kerslake, "The Kerslake Review", Labour controlled Lambeth council has wasted £25 million funding a failed private housing company, Homes for Lambeth. Worse, it appears at least one senior executive on a choice salary, Paul Simpson, was a former Labour Party staffer who made a career jump from one-man-band communications consultant to Head of Communications and Operations. Simpson's extensive LinkedIn profile takes credit for a number of areas which Kerslake said were failing. The author, Sam Smith of Matthew Hopkins News has written a lengthy and careful in-depth article . As well as raising the Kerslake Review, he raised historic issues since he worked with Simpson many years ago, which of course only he knows about, but which are consisten...

Biohackers: Bryan Johnson, Michael Lustgarten, and myself

Biohacking has come more into the public domain with the publicity around Bryan Johnson's blueprint . Bryan Johnson is someone who is a tech entrepreneur who sold one of his businesses a few years ago and has since being trying to improve his health. This has been described in the media as him spending about USD 2 million a year with try to get his body to be the equivalent of an 18 year olds. However, it is probably best to read his website (that I have linked to) to see what he describes this as. There are quite a lot of people who are doing similar things, but not necessarily spending as much or promoting what they are doing to the same extent. His website provides quite a bit of information, but sadly at the moment it is not as useful as it could be as he does not always link to the relevant research papers or specify the units of the measurements he quotes. Hopefully that will be fixed over time. Dr Michael Lustgarten is similar to Bryan Johnson in that he publicises...

Why does vitamin D exist - To provide an annual metabolic cycle?

We know Vitamin D exists. We know that people suffer if they don't have enough of it. However, it raises an interesting question as to why we evolved to create a vitamin in the summer which gets stored and then gradually fades away during the winter. I have an idea. Historically food was more plentiful in the summer and less available in the winter. The genes that rely on vitamin D don't function without it. Hence the body requires less energy. There are a number of things which operate to adjust metabolism to fit food availability. I think Vitamin D evolved to provide an annual metabolic cycle so things which could wait which required energy did not operate. That gives an idea as to what functions we would expect to depend on vitamin D. It would be those functions which are useful, but not essential all year round. The Vitamin D Receptor Inhibits the Respiratory Chain, Contributing to the Metabolic Switch that Is Essential for Cancer Cell Proliferation is an intere...

Autophagy, Gene Length and Aging (why Senolytics don't work that well)

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...

Its the long genes that stop working

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. ...

NMN, Nicotine Riboside and current controversies

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...

Blood Tests and Biohacking - some personal experiences worth reading

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...

Balanced Reporting and John Hemming v Sonia Poulton

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 ...

Interleukin-10 Review of Research

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...

What are the consequences of a shortage of nuclear Acetyl-CoA

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 ...