Foxo4-DRI
unknown riskAlso: D-peptide FOXO4 · Senolytic peptide · FOXO4 p53 disruptor
Foxo4-DRI is a D-amino acid retro-inverso peptide designed to disrupt the FOXO4-p53 interaction that keeps senescent cells alive. The 2017 Nature Medicine study showed clearance of senescent cells, improved fitness, and hair regrowth in aged mice. A new class of 'senolytic' peptides. No human trials completed.
Reported Benefits
Senescent cell clearance
Mouse study: cleared p16-positive senescent cells, restored physical fitness, reversed hair loss in naturally aged mice.
Anti-aging / rejuvenation
Proof-of-concept in mice; human translation entirely unknown.
Mechanism of Action
Interferes with FOXO4's ability to sequester p53 in senescent cell nuclei; liberates p53 to initiate apoptosis selectively in senescent (but not healthy) cells; clears SASP-secreting cells.
Key Clinical Studies
Baar et al. (2017)
Controlled · Animal (mouse)
Clearance of senescent cells; improved fitness, renal function, and fur density in aged mice
The Senolytic Class
Foxo4-DRI belongs to a new class of ‘senolytics’ — drugs that selectively kill senescent cells. Other senolytics include quercetin+dasatinib (small molecules). The peptide-based approach offers potential advantages in CNS penetration and selectivity.
The 2017 Nature Medicine paper was highly cited and generated enormous longevity research interest. Human translation remains entirely unknown.
Regulatory Status
Research OnlySafety Profile
Side Effects
- •Unknown in humans
- •Theoretical induction of apoptosis in beneficial senescent cells
Contraindications
- •Active cancer (senescent cells may have tumor-suppressive roles)
Primary Uses
Weekly Briefing
Regulatory updates + new study breakdowns.
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