Skip to main content

What are the consequences of a shortage of nuclear Acetyl-CoA

I am using this page to collate research papers looking at what disease are probably caused by differentation failure. It is at a really early stage at the moment. It has a useful collection of links, but no real analysis.

Atherosclerosis
Mummies reveal that clogged arteries plagued the ancient world Looks like it is not a modern diet
The Role and Research Progress of Inhibitor of Differentiation 1 in Atherosclerosis
Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment

Why do statins work?
I think it is clear that statins work. What they do is to prevent TCA (Tricarboxylic Acid) being converted into Cholesterol. This has two effects. A) Less Cholestoral, B) more TCA for other things. Clearly that would help with differentiation and would be a mechanistic route whereby Statins work.
Osteoporosis
Chromatin remodeling due to degradation of citrate carrier impairs osteogenesis of aged mesenchymal stem cells This paper blames a shortage of TCA outside the mitochondria for Osteoporosis
How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span This paper looks broadly at research on aging
Melatonin enhances osteoblastogenesis of senescent bone marrow stromal cells through NSD2-mediated chromatin remodelling This gives a mechanism for melatonin to help in Osteoporosis
Sarcopenia
Osteoporosis and Sarcopenia Increase Frailty Syndrome in the Elderly "Moreover, an alteration in mesenchymal stem cell differentiation is observed"
Geriatric muscle stem cells switch reversible quiescence into senescence
Muscle is a stage, and cells and factors are merely players these two link sarcopenia to stem cells not differentiating.
Diabetes (type 2) (and Fatty Liver)
Diabetes results from too much fat in the pancreas. This raises the question as to whether there is a differentiation issue with pancreatic cells where some of them end up as adipocytes when they shouldn't. A similar issue may exist for the Liver.
Rabbits and Plaque
Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties
NAFLD - Non alcoholic fatty liver disease
This also looks like a differentiation issue.
Nail Growth and Aging:
The Effect of Aging on the Rate of Linear Nail Growth
Nail Growth Rate Stem Cells
Human nail stem cells are retained but hypofunctional during aging
Hyperoxia
Increasing Oxygen Partial Pressures Induce a Distinct Transcriptional Response in Human PBMC: A Pilot Study on the “Normobaric Oxygen Paradox”
Telomeres
Human Telomerase and Its Regulation is a paper which indicates that telomeres are extended when the histone is more aceylated hypoacetylation is associated with shorter telomeres. Acetylation links to TCA levels outside the mitochondria.
Arthritis
The shortage of the protein FGF18, is sign of a gene expression problem which is likely to be an epigenetic acetylation issue.

General Stem Cell Paper
Potential of Stem Cell-Based Therapy to Restore Function in Aging Systems: Are We There Yet
Edit 26/12/2022
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan Edit 27/12/2022
Can you have too much Acetyl-CoA? I think the answer to this is yes. After a point non-enzymatic acetylations would start occurring in larger numbers. This would stop the cells being differentiated at all as proteins would be created at random.
The Metabolic Impact on Histone Acetylation and Transcription in Ageing

Comments

David Evans said…
Good to see an old Lib Dem warhorse finding a new cause to fight over. It's not an area I know anything about, but "Well done!"

And I wish you every success.
John Hemming said…
Thanks for this. In the end science is about truth rather than lobbying.
Willows said…
I very much like your find 'The Effect of Aging on the Rate of Linear Nail Growth'.

Popular posts from this blog

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.