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 be important. If you cannot chew up (and potentially spit out) waste products how can a cell handle the reprocessing of waste. However, there is also a key issue of ATP/O efficiency. This is the relationship between consumption of Oxygen and the provision of ATP. ATP is the main source of energy for cellular function. Cells can vary as to how efficient they are. The less efficient cells produce less ATP given the amount of Oxygen and glucose provided (and probably have more heat, but that may not be that important). Mitochondria deteriorate as a result of odd chemical reactions where reactive chemicals (ROS and RNS also called Free Radicals) end up reacting with the functional parts of the mitochondria rather than chemicals the cell makes to neutralise them (anti-Oxidants). What can happen, however, is that new mitochondria can be created. Once created they are more efficient. Autophagy (specifically mitophagy) can be used to get rid of the less efficient mitochondria so once the new mitochondria are created the cell becomes more efficient in the round.
Readers of my blog will be aware I have two big concerns about cellular health. One is the transcription of genes into mRNA and the second is the translation of that mRNA into protein. Both of these are key things as to when a cell is doing its thing.
It is very obvious that when a cell does not produce certain proteins things go wrong. This is the primary cause of many of the disease of aging (not necessarily all of them, but definitely the majority).
I have written before about what I think the mechanism is whereby transcription fails and the cause of this.
One topic that many of the people presenting on at The Autophagy network was the relationship between autophagy and longevity. Longevity is a pretty good test for the broader health of a living creature. Hence if experiments are done with an intervention that compare how long a control group of animals live and the time animals subject to an intervention live then it is a good test as to whether the intervention improves the health of the animals.
One presentation that was particularly interesting was by Malgorzata Zatyka of Birmingham University. This looked at the relevance of ribosomes to longevity. The Ribosomes are responsible for translation of mRNA into proteins. She reported that if cells had fewer copies of the Ribosome then the animals the cells were in lived longer. To me this supports my previous hypothesis that there is a problem which arises from a shortage of raw materials (substrate) to manufacture proteins which causes the ribosomes to go wrong in some way. Obviously if the Ribosomes do not produce the right protein then in some way the cell will be inclined to malfunction.
Malgorzata Zatyka's presentation also talked about different types of protein creation failure. I have not yet found the references to the original papers on this. However, it fits with the hypothesis that a shortage of substrate causes translation to go wrong. It is quite easy to understand how this might happen. Clearly the Ribosome pauses whilst it waits for its raw materials.
I have found this useful paper on Ribosome Quality Control. This explains that when the Ribosomes stall (which is a more permanent step beyond pausing) protein creation can be stopped and the products sent to a form of recycling which may include autophagy.
This is where a poster produced by Nicoll Matthews of the Institute of Cancer Research comes in. She had studied the interrelationship and links between various parts of cellular mechanism and found quite a few links between the Ribosome and the machinery of autophagy.
I have seen a number of examples in the literature where in aged cells the cells is short of a particular protein whilst at the same time there are actually quite a few copies of the relevant mRNA in the cell. This would be a likely outcome if the process of translation (protein creation) broke down. Logically a process which takes longer (for a longer protein) is more likely to fail particularly if the process is paused for quite some time.
Ribosome stalling is known to be caused by a shortage of nutrients, heat shock and oxidative stress. A cell with bad quality mitochondria is likely to suffer from more oxidative stress (and have less ATP).
Autophagy, of course, is not only important to this because of the recycling of failed protein creation, but also because a more efficient cell will produce more ATP for the same amount of Oxygen and Glucose. It does seem clear that this lies behind the difficulties with translation that occur as a cell deteriorates over time. Hence as well as dealing with Acetyl-CoA shortage people need to look at how they can ensure sufficient autophagy occurs. Interestingly and unsurprisingly too much Autophagy is bad for longevity and hence health. This is not surprising as you would not really want the cells to recycle well functioning parts of the cell. For a period of time the cell could be short of mitochondria, for example and this would cause a shortage of ATP and potentially tricarboxylate.
I will continue to try to get more information about the presentation from Malgorzata Zatyka and Nicoll Matthew's poster and will update this post when I get that.
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 be important. If you cannot chew up (and potentially spit out) waste products how can a cell handle the reprocessing of waste. However, there is also a key issue of ATP/O efficiency. This is the relationship between consumption of Oxygen and the provision of ATP. ATP is the main source of energy for cellular function. Cells can vary as to how efficient they are. The less efficient cells produce less ATP given the amount of Oxygen and glucose provided (and probably have more heat, but that may not be that important). Mitochondria deteriorate as a result of odd chemical reactions where reactive chemicals (ROS and RNS also called Free Radicals) end up reacting with the functional parts of the mitochondria rather than chemicals the cell makes to neutralise them (anti-Oxidants). What can happen, however, is that new mitochondria can be created. Once created they are more efficient. Autophagy (specifically mitophagy) can be used to get rid of the less efficient mitochondria so once the new mitochondria are created the cell becomes more efficient in the round.
Readers of my blog will be aware I have two big concerns about cellular health. One is the transcription of genes into mRNA and the second is the translation of that mRNA into protein. Both of these are key things as to when a cell is doing its thing.
It is very obvious that when a cell does not produce certain proteins things go wrong. This is the primary cause of many of the disease of aging (not necessarily all of them, but definitely the majority).
I have written before about what I think the mechanism is whereby transcription fails and the cause of this.
One topic that many of the people presenting on at The Autophagy network was the relationship between autophagy and longevity. Longevity is a pretty good test for the broader health of a living creature. Hence if experiments are done with an intervention that compare how long a control group of animals live and the time animals subject to an intervention live then it is a good test as to whether the intervention improves the health of the animals.
One presentation that was particularly interesting was by Malgorzata Zatyka of Birmingham University. This looked at the relevance of ribosomes to longevity. The Ribosomes are responsible for translation of mRNA into proteins. She reported that if cells had fewer copies of the Ribosome then the animals the cells were in lived longer. To me this supports my previous hypothesis that there is a problem which arises from a shortage of raw materials (substrate) to manufacture proteins which causes the ribosomes to go wrong in some way. Obviously if the Ribosomes do not produce the right protein then in some way the cell will be inclined to malfunction.
Malgorzata Zatyka's presentation also talked about different types of protein creation failure. I have not yet found the references to the original papers on this. However, it fits with the hypothesis that a shortage of substrate causes translation to go wrong. It is quite easy to understand how this might happen. Clearly the Ribosome pauses whilst it waits for its raw materials.
I have found this useful paper on Ribosome Quality Control. This explains that when the Ribosomes stall (which is a more permanent step beyond pausing) protein creation can be stopped and the products sent to a form of recycling which may include autophagy.
This is where a poster produced by Nicoll Matthews of the Institute of Cancer Research comes in. She had studied the interrelationship and links between various parts of cellular mechanism and found quite a few links between the Ribosome and the machinery of autophagy.
I have seen a number of examples in the literature where in aged cells the cells is short of a particular protein whilst at the same time there are actually quite a few copies of the relevant mRNA in the cell. This would be a likely outcome if the process of translation (protein creation) broke down. Logically a process which takes longer (for a longer protein) is more likely to fail particularly if the process is paused for quite some time.
Ribosome stalling is known to be caused by a shortage of nutrients, heat shock and oxidative stress. A cell with bad quality mitochondria is likely to suffer from more oxidative stress (and have less ATP).
Autophagy, of course, is not only important to this because of the recycling of failed protein creation, but also because a more efficient cell will produce more ATP for the same amount of Oxygen and Glucose. It does seem clear that this lies behind the difficulties with translation that occur as a cell deteriorates over time. Hence as well as dealing with Acetyl-CoA shortage people need to look at how they can ensure sufficient autophagy occurs. Interestingly and unsurprisingly too much Autophagy is bad for longevity and hence health. This is not surprising as you would not really want the cells to recycle well functioning parts of the cell. For a period of time the cell could be short of mitochondria, for example and this would cause a shortage of ATP and potentially tricarboxylate.
I will continue to try to get more information about the presentation from Malgorzata Zatyka and Nicoll Matthew's poster and will update this post when I get that.
Comments