Longevity & AgingFOXO4 Senses Oxidative Stress Through Cysteines and Keeps Senescent Cells Alive via p53
FOXO4 is a transcription factor that reacts to oxidative stress and helps senescent cells survive. This structured narrative review graded 89 publications by how directly they tested FOXO4 rather than other FOXO proteins. The strongest FOXO4-specific evidence covers three areas: sensing of reactive oxygen species through cysteine disulfides, stress-driven nuclear import and coactivator binding (transportin-1 and p300/CBP), and FOXO4 binding to p53 to keep senescent cells from dying. Evidence that FOXO4 itself drives antioxidant genes such as SOD2 and catalase is weak and mostly inferred from FOXO3. The senolytic peptide FOXO4-DRI clears senescent cells in mice, including endothelial cells, but has never been tested in humans. Safety, delivery and tumor-surveillance questions remain open.
