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Why are babies born young?

babies mitochondria

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#1 johnhemming

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Posted 06 June 2024 - 02:25 PM


https://johnhemming....born-young.html

 

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 getting enough of a chemical called Acetyl-CoA then it does not produce all the proteins. This is because acetyl-CoA is need to open up the DNA via a protein called the histone. Otherwise messenger RNA is not produced properly for the protein.

The main source, but not the only one, of acetyl-CoA is from a molecule called citrate which comes out of the mitochondria. There is another protein called the citrate carrier which sits in the membrane of the mitochondria which transfers citrate out of the mitochondrion. The level of citrate transport can be affected by two things. One is the number of citrate carriers in the membrane, the other is the mitochondrial membrane potential.

The Mitochondrial Membrane Potential is a sign of how much power the mitochondrion has. If it has a higher MMP it can transport more citrate molecules out of the cell (each together with a single proton).

Mitochondria are unusual parts of the cell (organelles) because they have some of their own DNA. This is stored in the mitochondrion and there can be more than one copy in each mitochondrion. The copies, however, are not necessarily exact copies and can vary. Also you can have different DNA in different mitochondria in the same cell. The level of variation in mtDNA is called heteroplasmy.

If the Mitochondrial DNA (mtDNA) is damaged then it can make the mitochondria less efficient and hence reduce the MMP. There are systems in the body that try to find the inefficient mitochondria and recycle them, but they are not perfect. Hence if mtDNA is damaged then mitochondria will become less efficient and the cell won't produce the full range of proteins that it should (aka be old).

Sadly the Mitochondria also produce molecules that are quite dangerous because they can react with other parts of the cell and cause damage. These are called variously Oxidants, Free Radicals and Reactive Oxygen/Nitrogen species. Hence a functioning mitochondrion can damage itself and in doing so damage the cell. The existance of multiple different types of mtDNA from damage is called heteroplasmy.

An old mother, therefore, will have cells with a mixture of mitochondria. Some are efficient with a high MMP and some are not. However, if those mitochondria were transferred to the egg unchanged then the egg would start out with a disadvantage. Hence what happens is that there is a mtDNA bottleneck which reduces the number of mitochondria that are transferred.

When the egg is fertilised all the mitochondria in the sperm are destroyed. This means that only the narrow range of mitochondria that come from the mother are kept in the cell. Then the cell needs to develop. Many egg cells at this point stop reproducing because they are not efficient enough. This happens more for older mothers which is why fertility becomes an issue. However, if a fertilised cell survives to being born this normally means it will have efficient mitochondria with a high MMP and the baby will be born biologically young.

So that answers the question as to why babies are born young. It also explains the different between paternal fertility and maternal fertility. It does raise other questions. It is clear that menopause is a result of the same deterioration of protein production as an early menopause implies earlier diseases of aging. It raises an interesting question as to whether puberty is also timed in the same way. It could be that mtDNA deterioration in certain tissues cause puberty. This as yet is unclear. There does appear to be a link between precocious puberty and early menopause. There are also questions as to what can be done about these things to improve health. Those really are questions for another post.


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#2 QuestforLife

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Posted 11 June 2024 - 02:04 PM

You put together an interesting hypothesis. Of course, many interesting hypotheses may explain why babies are born young. I do like your idea of mitochondrial decay being a timing mechanism for menopause and potentially puberty too. I do think it is unlikely however, for a couple of reasons. To start with, people with parkinson's have massively lower rates of mitochondrial turnover, but don't start getting problems until they are old, in the most mitochondrially dense neurons. All the rest of their tissues have messed up mitochondria, but they're still good enough in those tissues. I haven't seen any data showing they go through puberty earlier, or even meopause earlier. More likely there is another factor that drives both maturity (puberty) and arrival at old age. You also get people the other way around, say old cyclists, who have astonishingly pristine mitochondria (according to some measures, anyway). And despite being very fit, they are still obviously old, and die pretty much on schedule. There are also some problems with acetyl-coA being the primary cause of reduced gene expression. Firstly,  we get plenty of it with food, an in fact we probably get too much of it (hence fat people having downregulated pryuvate dehydrogenase). It might be that too much of a good thing is bad, and that fat people having reduced metabolic rate is actually a way of the body protecting itself from self harm. But it is still a stretch to pin gene expression changes to that one molecule. 

 

I do agree with you that sexual reproduction is basically a series of challenges to weed out unhealthy sperm and eggs, and it is pretty robust. I wonder what the health of people born through IVF is compared to natural birth. The first ones must be mid forties now...


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#3 johnhemming

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Posted 11 June 2024 - 02:19 PM

IVF does not guarantee a fertilised egg goes to term.

 

Mitochondria can deteriorate without fission or fusion.  In fact mitochondria can deteriorate then fuse.

 

The question on parkinsons is whether there is another genetic aspect which means that they are more sensitive to mitochondrial failure.



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#4 QuestforLife

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Posted 11 June 2024 - 03:30 PM

IVF does not guarantee a fertilised egg goes to term.

 

Mitochondria can deteriorate without fission or fusion.  In fact mitochondria can deteriorate then fuse.

 

The question on parkinsons is whether there is another genetic aspect which means that they are more sensitive to mitochondrial failure.

 

Thank you for those random facts. How do they support your theory?



#5 johnhemming

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Posted 11 June 2024 - 04:52 PM

The hypothesis stands on the basic article as written previously.  If the facts that I have listed which I did in response to your post and are not, therefore, random, do not explain why I disagree with your reasoning then please explain why?

 



#6 QuestforLife

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Posted 11 June 2024 - 05:19 PM

IVF does not guarantee a fertilised egg goes to term.

I'm aware. I made the point that IVF babies might have lower mitochondrial quality, because of reduced selection events, which might support your thesis. What say you?


Mitochondria can deteriorate without fission or fusion. In fact mitochondria can deteriorate then fuse.


And? Mitochondrial fusion often hides defects in what would be otherwise smaller mitochondria, and this may be part explanation for why parkinsons does not manifest earlier. Did you have a more general point to make?

The question on parkinsons is whether there is another genetic aspect which means that they are more sensitive to mitochondrial failure.


Not that I'm aware of. I assume you saying this to try and explain why parkinsons doesn't manifest as more general ageing, as per your theory?

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#7 johnhemming

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Posted 12 June 2024 - 01:03 PM

>I'm aware. I made the point that IVF babies might have lower mitochondrial quality, because of reduced selection events, which might support your thesis. What say you?
 
Both are possible.  In the end it is not relevant to the thesis.
 
 
>And? Mitochondrial fusion often hides defects in what would be otherwise smaller mitochondria, and this may be part explanation for why parkinsons does not manifest earlier. Did you have a more general point to make?
 
I think it is probably the case that fusion does protect bad quality mitochondria which would have better been sent off to the autophagasome.  Hence you get lower energy malfunctional cells that are not easily improved by autophagy. This may be where interventions like Rapamycin help.
 
 
>Not that I'm aware of. I assume you saying this to try and explain why parkinsons doesn't manifest as more general ageing, as per your theory?
 
Why is Parkinsons not a disease of aging?
 
Different people respond differently to aging primarily because it is a tissue specific process, but also because some people may have genetic differences which make lower efficiency (greater aging) in particular cells more of an issue.
 





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