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Why are babies born young?

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.


nigel hunter said…
Citrates!? Mitochondria!? Are you saying that certain fruits and mushroom family foods should be part of a humans regular diet?

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Its the long genes that stop working

People who read my blog will be aware that I have for some time argued that most (if not all) diseases of aging are caused by cells not being able to produce enough of the right proteins. What happens is that certain genes stop functioning because of a metabolic imbalance. I was, however, mystified as to why it was always particular genes that stopped working. Recently, however, there have been three papers produced: Aging is associated with a systemic length-associated transcriptome imbalance Age- or lifestyle-induced accumulation of genotoxicity is associated with a generalized shutdown of long gene transcription and Gene Size Matters: An Analysis of Gene Length in the Human Genome From these it is obvious to see that the genes that stop working are the longer ones. To me it is therefore obvious that if there is a shortage of nuclear Acetyl-CoA then it would mean that the probability of longer Genes being transcribed would be reduced to a greater extent than shorter ones.