What is FOXO4-DRI?
FOXO4-DRI (FOXO4-D-Retro-Inverso) is a synthetic 46-amino acid peptide designed to selectively eliminate senescent cells -damaged cells that accumulate with age and secrete harmful inflammatory factors (SASP). The peptide uses D-amino acids in reversed sequence, making it resistant to proteolytic degradation while maintaining binding function. FOXO4-DRI works by disrupting the FOXO4-p53 interaction that keeps senescent cells alive, causing p53 nuclear exclusion and redirecting it to mitochondria to trigger apoptosis. In mouse studies, it restored fur density, renal function, and physical fitness in aged animals while protecting against chemotherapy-induced toxicity. Notably, it shows 11.73-fold selectivity for senescent over healthy cells.