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Showing posts from December, 2022

Autophagy, Gene Length and Aging (why Senolytics don't work that well)

Role of autophagy in aging: The good, the bad, and the ugly is a really good review into the function of autophagy (eating yourself) which is how cells tidy themselves up by getting rid of dysfunctional mitochondria and creating new ones. Autophagy is a good thing because it makes cells work better. That almost certainly ups the Acetyl-CoA levels in the nucleus which readers of this blog will know is a *Good Thing . [Incidentally if you have the time its worth reading all of the review] I will extract part of the review: Unfortunately, the protection afforded by autophagy is progressively erased with age. For instance, Atg5, Atg7, and Beclin 1 are down-regulated in the normal aging brain, whereas, in osteoarthritis, the levels of ULK1, Beclin 1, and LC3 fall (Rubinsztein et al., 2011). In hepatocytes of aged rats, alongside the increase in cytosolic Hsc70, and coordinate with decreased binding and lysosomal uptake of cargo, there is a significant rise in degradation and hence red

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.