Longevity
FOXO4-DRI
Senolytic peptide that disrupts the FOXO4-p53 interaction to induce selective apoptosis of senescent cells. Highly promising in mouse models, with minimal human evidence.
Research compound Longevity Anti-aging
- Full name
- FOXO4 D-Retro-Inverso peptide (senolytic)
- Also known as
- FOXO4-DRI
- Regulatory status
- Research compound | Preclinical-stage (mostly mouse models) | Not FDA approved for any indication
Origin
Developed at Utrecht University from the discovery that senescent cells depend on the FOXO4-p53 interaction for survival. A D-retro-inverso peptide (mirror-image, reversed-sequence variant) emerged around 2017 as senolytic therapy gained attention. Most published evidence is mouse-based.
Mechanism
Binds FOXO4, disrupting the FOXO4-p53 complex that normally shields senescent cells from apoptosis. Restoring p53 pro-apoptotic signaling in cells with high FOXO4-p53 complexes triggers selective apoptosis in senescent cells while sparing normal ones.
Research summary
Evidence
In aged mice, FOXO4-DRI reduces senescent cell burden across tissues and improves function/healthspan in some models, including Alzheimer's disease-model mice. A 2022 study found senolytic depletion (including FOXO4-DRI) paradoxically worsened pulmonary hypertension in mice, showing the effect is context-dependent. No published human trials exist as of 2026.
Evidence tier: Research compound — see the methodology note for how this is assessed.
Citations
Reported benefits
- selective apoptosis of senescent cells (mouse models)
- reduced senescent cell burden across tissues (mouse studies)
- improved organ function in aged mice (specific models)
Dosing protocols reported in the literature & community
These are protocols reported by compounding pharmacies, published trials, or self-experimentation communities — not a prescription. Start low, especially for anything new.
| Route | Reported protocol |
|---|---|
| Intravenous or intraperitoneal injection | Mouse studies: 5-10 mg/kg IV/IP 2-3x weekly. No established human protocol; community dosing entirely speculative. |
Side effects
- minimal direct toxicity reported in mouse studies
- potential harmful effects in specific disease contexts (e.g. worsened pulmonary hypertension)
- human safety essentially unknown
Safety notes
Community & reddit notes (anecdotal — not clinical evidence)
High enthusiasm in longevity communities based on mouse lifespan data, but real human experience is essentially nonexistent. The gap between mouse promise and human evidence is large.