John Hemming's Web Log

The idea that Parkinson's Disease (PD) is an accelerated form of brain aging has been around for quite a long time. However, as with aging more generally any hypothesis as to the mechanisms behind Parkinson's needs to explain all the known research data. I have been discussing PD with a number of people over the past few months. The results from research indicate that Parkinsons is not primarily caused by genetic factors. That is because there are studies where individual twins get Parkinsons, whilst their twin does not. I was wondering, therefore, what might be an alternative cause. This paper is one that substantiates the argument that normally the brain does not age as fast as the rest of the body. What we need to look at is what might cause this to happen. If we start with the assumption from my previous posts that aging results from the mutation of mitochondrial DNA (mtDNA) then we need to find something that prevents the mutation of mtDNA in the brain that does n...

Software Developer and Artifical Intelligence Expert Samuel Collingwood Smith has been working with me on a number of projects for a last few years, mostly in the Artificial Intelligence / AI / bio-hacking space. We entered a number of competitions, some of which were against billion dollar organisations and in one case came in the top-ten with software that runs on a desktop PC, on an nVidia card, against thirty other competitors. As well as using open source AI models hosted in Python, Smith has used his C# and C++ tools to develop his own scratch-written neural network engine, LearnSilver. This is a C# native neural network library that can also execute on CUDA enabled nVidia cards with C/C++, including many gaming graphics cards. It enable significant processing on consumer hardware. It supports training, serialisation of entire models with a single method call and recurrent networks. TALIS is a side, personal project Smith worked on prior to joining me in setting up our new AI c...

The Biohacking Team has withdrawn from XPRIZE Healthspan. We think the prize is a really good idea and the science behind the judging is really good. However, we are not willing to sign the competitors agreement. XPRIZE have asked that the competitors agreement be kept confidential and hence we should not give our reasons as to why we will not sign the competitors agreement. Signing the competitors agreement is a requirement for remaining in the contest, hence we need to withdraw. We wish XPRIZE Healthspan well. Finding out what can be done to increase the proportion of people's lives in good health is a really good idea. We have, however, decided to keep the team together. Although the team was brought together to compete in XPRIZE and we are no longer doing that, we have other things to do. We have already participated in the Biomarkers of Aging contest and the Medical Affairs Olympics. We are also running small scale biohacking coaching sessions on both the Diseases of ...

The Electron Transport Chain has five complexes. These are comprised of a number of subunits. What I find particularly interesting is that some of the proteins are generated via nuclear DNA and some of the proteins are generated via mitochondrial DNA. Most of the ROS (that damages mtDNA) is generated by Complexes 1 and 3. Complex 1 has 45 subunits in humans, but in fact only 7 of those (ND1, ND2, ND3, ND4, ND4L, ND5, ND6) are encoded by the mitochondrial genome. Complex 3, however, has 11 subunits only 1 of which is in mtDNA (MT-CYB) Complex 2 is entirely coded by the nucleus, Complex 4 has 3 (MT-CO1, MT-CO2, and MT-CO3) out of 13 units coded in mtDNA. ATP Synthase also called Complex 5 has 16 units two of which are encoded in the mitochondria. Hence it is clear that complex 1 is perhaps the key complex for mtDNA mutation linked aging and not surprising that this is the complex inhibited in Oocytes. There is an argument that for hydrophobic subunits the energy cost of transferr...

Oxygen is essential for human life. That is well known. However, the level of Oxygen in the atmosphere has interesting effects. I wrote previously about The Hypoxia Inducible Factor (HIF). HIF (particularly 1 alpha) is a molecule which signals cells to create proteins to build in response to stress. This can involve building new mitochondria or recycling old inefficient mitochondria. In essence it is ringing an alarm that calls for cells to get better prepared for stress. Interestingly HIF is switched on by a drop in the oxygen partial pressure (that proportion of air pressure that is oxygen). It is also well known that if brain cells get too little Oxygen then they can get harmed or die. Hence too low an Oxygen level causes brain damage. In fact there is evidence from people living at high altitudes that at a point the oxygen level is too low and this harms health. However, there is another aspect of Oxygen levels that relates to the mitochondria. The mitochondria produc...

There are a number of theoretical debates about aging. One is the question of whether we are "programmed to die". Those who believe this think that at a point creatures get to a stage where the organism at a cellular level starts processes which deliberately set out to end the life of the multicellular organism. Another potentially contradictory view is simply that creatures accumulate damage up the point at which they can no longer survive. It is possible, however, to look at different species and see how their lifespan operates. What is clear is that different species age in different ways. Some species don't age in the same way as others. It is worth having a look at how species vary and to what extent that explains the relationship between evolution and lifespan. Firstly, it is clear that there are species where the adult commits some form of suicide after mating. Octopuses and Pacific Salmon There are, however, also species which have negligible senes...

An interesting paper was published in the week before Christmas. Mitochondrial quality control: the real dawn of intervertebral disc degeneration? The summary states: Intervertebral disc degeneration is the most common disease in chronic musculoskeletal diseases and the main cause of low back pain, which seriously endangers social health level and increases people’s economic burden. Disc degeneration is characterized by NP cell apoptosis, extracellular matrix degradation and disc structure changes. It progresses with age and under the influence of mechanical overload, oxidative stress and genetics. Mitochondria are not only the energy factories of cells, but also participate in a variety of cellular functions such as calcium homeostasis, regulation of cell proliferation, and control of apoptosis. The mitochondrial quality control system involves many mechanisms such as mitochondrial gene regulation, mitochondrial protein import, mitophagy, and mitochondrial dynamics. A large numbe...

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...