FOXO4-DRI
An experimental compound under investigation for its potential to influence cellular senescence and healthy aging pathways.
Laboratory and educational research purposes only.What is FOXO4-DRI?
FOXO4-DRI (D-Retro-Inverso peptide) is an experimental senolytic peptide designed to selectively induce apoptosis (programmed cell death) in senescent cells (cells that stop dividing but refuse to die, driving aging and disease). It was developed by Peter de Keizer’s team in the Netherlands and is being studied for anti-aging, regenerative medicine, and cancer therapy.
Mechanism(s) of Action
FOXO4–p53 interaction blockade → Normally, FOXO4 binds to p53 in senescent cells, preventing apoptosis.
FOXO4-DRI disrupts this interaction.
This frees p53 to trigger apoptosis specifically in senescent cells.
Pathways involved:
p53 tumor suppressor pathway → initiates senescent cell death.
Cellular senescence pathway → removes dysfunctional “zombie” cells.
FOXO transcription factor pathway → regulates stress resistance and longevity.
This process is senolytic: clears senescent cells without affecting healthy, proliferating cells.
1. Anti-aging effects — removal of senescent cells rejuvenates tissues, improves stem cell function, and slows biological aging.
2. Tissue regeneration — improves recovery of organ systems (shown in mice: better kidney and liver function).
3. Increased vitality — in preclinical studies, treated mice regained fur density, exercise capacity, and organ function.
4. Cancer adjuvant potential — by removing senescent cells, may reduce pro-cancer inflammatory environment.
5. Improved stem cell activity — reduces “senescence-associated secretory phenotype” (SASP), restoring tissue microenvironments.
6. Possible neuroprotection — senescent cell clearance in brain models reduced neuroinflammation (experimental).
Summary:
FOXO4-DRI is a cutting-edge senolytic peptide that clears senescent cells via FOXO4–p53 pathway disruption, offering major potential for anti-aging, tissue rejuvenation, and regenerative medicine. Still early-stage, but highly promising in preclinical models.