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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.

Excess TCA outside the mitochondria

It does seem quite clear that there are likely to be negative consequences from too much TCA outside the mitochondria. Exactly what they are is unclear. However, this paper INDY—A New Link to Metabolic Regulation in Animals and Humans states: "Reduced expression of the Indy gene in flies and worms extends their longevity. INDY is expressed in the plasma membrane of metabolically active tissues. Decreased expression of Indy in worms, flies, mice, and rats alters metabolism in a manner similar to calorie restriction. Reducing INDY activity prevents weight gain in flies, worms, and mice, and counteracts the negative effects of age or a high fat diet on metabolism and insulin sensitivity. "
General Stem Cell Paper
Potential of Stem Cell-Based Therapy to Restore Function in Aging Systems: Are We There Yet

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.

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