Its the long genes that stop working

https://johnhemming.blogspot.com/2022/12/its-long-genes-that-stop-working.html

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. That is because the availability of the whole of the gene will be reduced by a multiple of the probabilities of shorter genes being available. The process of acetylation for which Acetyl-CoA is required opens up the genes so that they can be encoded. That does explain now why probability comes into so much of transcription and the balance of the probabilities of shorter genes being transcribed and longer genes being transcribed.

The interesting thing, however, is that my experimentation points to this as being at least to some extent a reversible process. What that means, of course, is that to some limited extent the effect of this can be mitigated improving people's healthspan even if it has no effect on the maximal life span.

https://www.youtube.com/watch?v=ISo8rGkMR9o