A senolytic peptide that selectively triggers apoptosis in senescent cells while sparing healthy tissue.
Retro-inverso D-amino acid peptide that penetrates cells and disrupts the interaction between FOXO4 (a transcription factor overexpressed in senescent cells) and p53. In normal cells, FOXO4-p53 interaction is low. In senescent cells, FOXO4 sequesters p53 in the nucleus to prevent apoptosis — FOXO4-DRI breaks this interaction, freeing p53 to trigger programmed cell death selectively in senescent cells.
Published in Cell (2017) by de Keizer et al., FOXO4-DRI reversed multiple age-related phenotypes in fast-ageing and naturally aged mice — including restoring fur density, fitness, and kidney function — without apparent toxicity to normal tissues.
Senolytics (senescent cell-clearing agents) represent a growing frontier in ageing biology. FOXO4-DRI's high selectivity for senescent versus normal cells distinguishes it from broader senolytics like dasatinib/quercetin.