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FOXO4-DRI is a synthetic peptide designed by Baar and colleagues at Erasmus University Medical Center and published in Cell in 2017, and its mechanism is a deliberate act of sabotage on a survival pathway. Senescent cells are cells that have permanently exited the cell cycle after damage; they resist apoptosis and accumulate with age while secreting inflammatory factors. Part of what keeps them alive is FOXO4, a forkhead transcription factor that is upregulated in senescence and binds p53, holding it sequestered in the nucleus where it cannot travel to the mitochondria and trigger apoptosis. FOXO4-DRI is a peptide modelled on the FOXO4 region that contacts p53; introduced into a cell it competes for that interface, displaces p53 from FOXO4, and allows p53 to relocate and initiate cell-intrinsic apoptosis. Non-senescent cells do not carry the same elevated FOXO4 and are largely spared, which is the basis of the selectivity. The D-retro-inverso construction — the sequence reversed and built from D-amino acids — preserves the three-dimensional arrangement of side chains that does the binding while making the peptide unrecognisable to proteases.