Register here for @R42groups’s longevity event:
https://us02web.zoom.us/meeting/register/tZAsceGsrTwuH9ME0iR618csjjogqE-EALFJ#/registration…
Longevity is a hot topic these days. Another hot topic is space travel, with a new race back to the Moon and potentially Mars. But both of these exciting movements impact the smallest and most crucial part of our bodies: mitochondria, tiny organelles that generate power for our cells and our every action.
Luckily, a new wave of research in the past decade has given us powerful new techniques to protect and potentially even replace mitochondria damaged due to aging, the radiation and low gravity of space travel, or diseases such as Covid-19.
Join special guest presenter Scott Parazynski, former NASA astronaut, Stanford-trained “space doctor”, and veteran of Shuttle flights and 7 spacewalks. Also presenting will be Tom Benson, CEO of Mitrix Bio Inc, the developers of the Mitochondrial Bioreactor and mitochondrial transplantation, and Dr. Benedict Albensi, PhD, Chair of Department of Pharmaceutical Sciences at NSU Florida and recognized expert in Mitochondria and Neurodegenerative disease.
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I don’t know who else from Rapamycin News attended this, but it was really quite good. I tend to attend remote events. It does not normally suit me to travel because of my other commitments.
The discussion about Mitochondria was particularly interesting. I had been working on the assumption that the damage to Mitochondria that occurs over time was oxidative stress and damage to the Electron Transport Chain (ETC). However, it is clear that Mitochondrial DNA (mtDNA) is damaged as people get older and, although there are multiple copies of mtDNA in each mitochondrion, the damage would still have an effect.
For those that don’t know the subtleties on this we have two types of DNA in our cells. We have DNA in the nucleus. That is inherited from both parents, but the mitochondria also have DNA actually inside the mitochondrion itself. This comes from the mitochondria in the egg and hence is entirely inherited from the mother. The mitochondria are built by a mixture of proteins created by the nuclear DNA and the ribosome, but also in part from proteins created by mtDNA.
mtDNA is particularly vulnerable to oxidative stress because it is not spooled around a histone. Nuclear DNA is wrapped around some proteins called Histones. This protects it from damage much of the time. However mtDNA does not have a histone.
Tom Benson’s presentation compared three generations of his family and how damaged the mtDNA was. Unsurprisingly the older people got the more damaged the mtDNA. This would logically cause breakdown in the homeostasis of the ETC and a reduction in mitochondrial efficiency.
There is an interesting thought here in that if people do not get enough sleep and don’t generate enough pineal melatonin then the process of topping up mitochondrial melatonin via the serum does not function well. Hence mtDNA would get more damaged. It brings also the interesting thought that some of the anti-puberty effects of melatonin may arise from protection of mtDNA.
Melatonin is also generated in the mitochondria themselves, but there is a limit as to how much can be produced hence a top up has sense.
However, it would explain how melatonin achieves its various anti-cancer effects etc (if that is the case), by particularly protecting mtDNA from damage so that as autophagy occurs and the quality control operates on mitochondria then the resultant set of mtDNA does not deteriorate as quickly.
Still hopefully R42 will put up this as a free to air video.
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I thought I should add something from Tom Benson’s presentation.
People in this forum probably already know that the body transplants mitochondria between cells at times via the blood in Extracellular Vesicles (EVs). Those which contain mitochondria are quite a bit bigger than most of them (most are about 30 nn and the mitochondria ones are from memory 800nm (maybe 600).).
Mitrix Bio aim to grow new mitochondria and transplant them via mitlets which are in essence big EVs (they are EVs with mitochondria in them).
Mitochondrial transplant is being done for various diseases and does work in certain circumstances.
What is being found, however, is that it is easy to give too high a dose of mitochondria and also that the energy effect of new mitochondria dies away quite quickly as the cells adjust to the new circumstances.
[Thinking about this it could be linked to cytosolic acetyl-CoA levels and the cell thinking those are too high and so taking actions to reduce energy prouction.]
However, I do think the idea of fixing mitochondrial DNA via transplanted mitochondria is a useful thought although I think the body already copes with a certain amount of inefficiency when it comes to mitochondria.
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John, thanks for the report back on the webinar. I agree that Mitrix looks extremely interesting and I hope they get funding to move forward.
We’ve discussed them (and I’ve included some slides from their presentation at the Longevity Summit) in past posts. For people are interested in learning more: Mitochondrial Medicine, Podcast with Tom Benson of Mitrix Bio
Mitrix presentation here: Highlights from the 2023 Longevity Summit
I have more recently been doing further study on mtDNA. It is clear that there is an argument that failures by DNA Polymerase gamma are the cause of a lot of mtDNA mutations moreso than ROS. However, I don’t as yet know what a considered analysis of the evidence would lead me to conclude and it clearly will take me some hours to get an idea about this (hours I don’t have at the moment).
Hence I make the point that what I say above may not be accurate. Thinking about mechanisms if mtDNA mutation is an issue caused by failure of replication then one would not expect mitophagy to overcome this. Clearly mitophagy/autophagy has positive effects. Hence I can see that this project will take me some time.
Here is an article published two days ago.
Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout ageing
https://www.nature.com/articles/s41559-024-02338-3
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