John Hemming's Web Log

The fact that mitochondria have their own DNA has been known for a number of decades. However, reading that DNA is harder than the nuclear DNA. That is because there are multiple copies of the DNA in individual mitochondria as well as there being more than one mitochondrion in most cells. However, science has now developed techniques for analysing the mitochondrial DNA in quite subtle detail. In 2024 a number of interesting papers were produced which I will talk about in this post The rate and nature of mitochondrial DNA mutations in human pedigrees is paper produced by a number of researchers in Iceland. The abstract states: We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position...

I have seen a surprisingly upbeat post from Sonia Poulton about Sam Smith’s appeal against her. In fact, like so much of what she says, she is misleading her followers. To explain briefly, earlier this year Sam and I applied to strike out parts of Sonia’s case in the ongoing lawsuit between Sonia on one side, myself Sam and Darren Laverty on the other. Sam helped with both applications along with two barristers. They were heard on 1 May 2024. The first application won - part of Sonia’s case was struck out as inconsistent with an earlier witness statement. Some would call that, “lies”. Sonia did not appeal. The rest of the strike-outs failed. After taking advice from counsel, Sam appealed and got permission from Mrs Justice Steyn DBE. The appeal failed, except that the judge ordered Sonia to clarify her case in a formal statement called a Part 18 Response. In effect, she abandoned 11 of the 21 pleadings we were trying to strike out, promising not to rely on them or file evidence on t...

Biohacking to Improve Everyone's Health, the team of Biohackers intending to compete in XPRIZE Healthspan, have reached the top ten in prediction of mortality using methylation data in the second round of the Biomarkers of Aging competition. The contest aims to use data on methylation of DNA sites and other biomarkers to determine the biological age of individuals and predict outcomes such as mortality. The Biohacking team, including software developer and machine learning expert Samuel Collingwood Smith, used their own proprietary software called LearnSilver to develop their prediction models, in combination with other tools. LearnSilver is a .NET C# / C++ / CUDA software library that allows execution of complex neural networks, including recurrent networks, on consumer hardware along with efficient serialisation. The library can execute in single-threaded mode on a CPU, or multi-threaded mode and it can also leverage nVidia hardware for massively parallel operations. Sam Smit...

Biohacking to Improve Everyone's Health , the team of Biohackers intending to compete in XPRIZE Healthspan, have won some early prizes in the 2024 MEDICAL AFFAIRS INNOVATION OLYMPICS #MAIO2024 . The MAIO is organised by The Medical Affairs Professional Society and sponsored by a number of leading biotech companies including Amadea Pharma . Of all of the biotech groups proposing ideas the Biohacking Team won the "high jump" the prize for the most lofty idea. The team also got the overall bronze award in Patient Centricity. John Hemming, leader of the Biohacking Team said, "I am pleased that the MAIO recognised our proposal for improving gene expression as being the most 'idealistic, lofty concept with a vision' of the varied ideas being presented at the contest. Our challenge, of course, is to refine the proposal and demonstrate that it broadly has beneficial effects in extending healthspan." These are the main two presentations at the MAIO 202...

When it comes to development there are a number of steps which can be quite well defined. One, of course, is death. Another is birth. Then there is sexual maturity and for some people menopause. There are plenty of papers which link precocious puberty with early menopause. There are also those which link early menopause with higher mortality and earlier age based diseases. This points to those being driven by the mRNA splicing changes and other changes in mRNA transcription primarily from the average mitochondrial membrane potential. I was wondering recently, however, about birth. Is that step potentially driven by MMP. There are a number of pieces of evidence that point to this. One is that mothers who were born prematurely are also likely to have premature children. Importantly people who are born prematurely also face health problems in their lives at an earlier stage. An overview of adult health outcomes after preterm birth " Large cohort studies have shown that ...

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 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? 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...

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 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...

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...

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

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...

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...

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 ...

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...

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...

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...

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. ...