β-hydroxybutyrate is interesting because in ketosis it can be around at a millimolar level which has significant HDAC inhibitory effects (or perhaps more precisely KDAC). I have not myself seen the same argument made for acetoacetate or acetone.
Q re acetone
Q more generally
Interestingly acetoacetate appears to be a weaker KDAC inhibitor (If anyone is interested in this the second chatGPT is worth reading).
Acetate itself has interesting functions, but operates homeostasis within the cell which means it is not that good as an exogenous intervention (unlike citrate)
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Within the context of this KE4 is potentially an interesting supplement or any other ketone ester that produces beta hb.
John, this seems interesting and relevant to perhaps your favorite topic. How generalizable do you think this research is, to aging and cellular senescence?
HDAC2 inhibition restores H4K16 Acetylation and Rescues Cellular Senescence in Hutchinson-Gilford progeria syndrome
The effects of HDAC2 inhibition on cellular senescence and nuclear morphology suggests that HDAC2-mediated histone deacetylation contributes directly to the pathological features of HGPS, extending the functional impact of HDAC2 inhibition beyond DNA repair defects to fundamental aspects of cellular aging.
Rana Karimpour, Mzwanele Ngubo, William L Stanford and Michael Hendzel
bioRxiv. posted 7 November 2025, 10.1101/2025.11.07.687234
http://biorxiv.org/content/early/2025/11/07/2025.11.07.687234
I think general inhibition of deacetylation is helpful, but only up to a point.