The anti-senescence effect of D-β-hydroxybutyrate in Hutchinson-Gilford progeria syndrome involves progerin clearance by the activation of the AMPK-mTOR-autophagy pathway

This in vitro study examined the effect of D-beta-hydroxybutyrate (BHB) on cellular models of Hutchinson-Gilford progeria syndrome (HGPS), which is caused by the aberrant protein progerin. BHB improved nuclear and nucleolar morphometrics, diminished the senescence phenotype, enhanced degradation of SQSTM1/p62 consistent with stimulated autophagic flux, and decreased progerin abundance. Inhibitors of AMPK and of ULK1/2 and AMPK reversed the BHB-induced progerin decline and its anti-senescent effect.