FOXO4-DRI
The most targeted senolytic discovered — kills senescent cells by disrupting p53 survival signalling. Dramatic results in mouse ageing.
Research facts
| Half-life | ~24h (estimated) |
|---|---|
| Route | IP (animal studies) / SubQ (experimental human) |
| Typical dose | 5 mg/kg 3× weekly (mouse studies — no human dose established) |
| Frequency | Intermittent (3× weekly in mouse studies) |
| Solvent | DMSO/PBS |
| pH | N/A |
| Stability | Frozen |
Mechanism of action
FOXO4-DRI is a retro-inverso peptide designed to disrupt the interaction between FOXO4 and p53. Senescent cells (cells that have permanently stopped dividing but resist death) survive by upregulating FOXO4, which sequesters p53 in the nucleus and prevents apoptosis. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, freeing p53 to initiate apoptosis specifically in senescent cells. In aged mice, FOXO4-DRI cleared senescent cells, restored exercise capacity, fur density, and renal function, and extended lifespan. The 2017 Cell paper by van Deursen/de Keizer was landmark in the senolytic field.
Documented effects (research-model)
- Most targeted senolytic — selectively kills senescent cells via p53
- Landmark 2017 Cell paper: restored exercise capacity, appearance, and renal function in aged mice
- Strong mechanistic rationale for extending healthspan
- Potential in frailty, age-related sarcopaenia, and renal decline
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Research Only | No established human dose — 5 mg/kg 3×/week in mice | Intermittent cycles | Unknown for humans | DMSO-based research solution |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- NAD+ MODERATE
Senolytics clear senescent cells; NAD+ supports mitochondrial function in remaining healthy cells. Complementary healthspan interventions.
Myths & misconceptions
Evidence gaps
- No human clinical trial data.
- Effect of selectively killing senescent cells on human tissue repair (senescent cells have some beneficial paracrine roles) not fully characterised.
- Optimal dosing, cycle length, and washout in humans completely unknown.
Safety notes
No human safety data. Disrupting p53 function selectively in senescent cells is the target — but off-target p53 effects are theoretically concerning (p53 suppresses cancer). Research context strictly maintained. Not for human therapeutic use.
Biomarkers to monitor
Primary-source citations
- PMID 28253321 — FOXO4-DRI alleviates age-related metabolic disfunctions and physical deterioration via clearance of senescent cells (Cell. 2017)
Frequently asked
What is FOXO4-DRI?
FOXO4-DRI (FOXO4-p53 Interaction Disruptor — Senolytic Peptide) is a research compound classified in our library as Tier D — Animal or in-vitro data only.. The most targeted senolytic discovered — kills senescent cells by disrupting p53 survival signalling. Dramatic results in mouse ageing.
What is the evidence tier for FOXO4-DRI?
We classify FOXO4-DRI as Tier D: Animal or in-vitro data only. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of FOXO4-DRI?
For FOXO4-DRI, typical research dose is 5 mg/kg 3× weekly (mouse studies — no human dose established), route is IP (animal studies) / SubQ (experimental human), half-life is ~24h (estimated). Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
Is FOXO4-DRI safe?
No human safety data. Disrupting p53 function selectively in senescent cells is the target — but off-target p53 effects are theoretically concerning (p53 suppresses cancer). Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.