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The Electron Transport Chain, DNA and aging - does evolution intentionally expose the Electron Transfer Process to mitochondrial DNA damage?

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...
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Aging, Development, and Living at High Altitudes (Oxygen Levels)

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...
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Are we programmed to die?

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...
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How to fix the Extra Cellular Matrix - Fix the Mitochondria

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...
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Subtle details of mitochondrial DNA are revealed showing the underlying biochemical cause of aging

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...
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Sonia Poulton Abandons Large Parts of Case

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...
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Biohacking to Improve Everyone's Health Reaches Top Ten in 2nd Round of Biomarkers of Aging Competition

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...
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