FOXO4-DRI
FOXO4-DRI (senolytic peptide)
An experimental senolytic peptide that selectively triggers death of senescent cells in animal studies.
Overview
FOXO4-DRI is a designed peptide that disrupts the interaction between FOXO4 and p53 inside senescent cells, releasing p53 to trigger their apoptosis. In progeroid and aged mice it reversed markers of frailty and improved organ function. It is an early proof of concept with no human trials, so the evidence is preliminary.
Mechanism of action
Disrupts the FOXO4-p53 interaction selectively in senescent cells, allowing p53 to initiate targeted apoptosis of those cells.
Key studies & citations
- Animal2017
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
A designed FOXO4 peptide that blocks the FOXO4-p53 interaction selectively triggered apoptosis in senescent cells and restored fitness, fur density and renal function in fast-aging XpdTTD/TTD and naturally aged mice.
Cell - Animal2020
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Independent replication of the mechanism: FOXO4-DRI induced p53 nuclear exclusion and apoptosis in senescent Leydig cells and improved testosterone secretion in naturally aged mice.
Aging
Frequently asked questions
Has FOXO4-DRI been tested in humans?
No. The landmark evidence is from mouse studies. There are no human clinical trials, so it remains experimental.