FOXO4-DRI

FOXO4-DRI is a D-retro-inverso (DRI) peptide — all D-amino acids in reverse sequence — designed to penetrate cells and disrupt the physical interaction between FOXO4 and p53 in senescent cells. Normally, nuclear FOXO4 binds p53 and prevents it from triggering apoptosis in senescent cells.

In senescent cells, FOXO4 accumulates in the nucleus and binds p53, preventing apoptosis. FOXO4-DRI competitively displaces FOXO4 from p53, allowing p53 to initiate mitochondrial apoptosis selectively in senescent cells — sparing normal, healthy cells which don't rely on this anti-apoptotic mechanism.

Landmark Nature Medicine 2017 study demonstrated FOXO4-DRI cleared senescent cells from aging mice, restoring physical fitness (grip strength, running distance), fur density, and kidney function. Survival was extended. This was the first demonstration that targeted senolytic therapy could reverse physical aging phenotypes.

Store lyophilized at -20°C. DRI peptides are highly resistant to enzymatic degradation due to D-amino acid backbone. Reconstituted solution stable 60+ days at 2–8°C.