FOXO4-DRI
FOXO4-D-Retro-Inverso · Proxofim
D-retro-inverso FOXO4/p53 interfering peptide from Baar 2017 mouse senolytic work. Not a frailty drug. Do not scale 5–20 mg/kg mouse doses onto a human. Gray-market D-peptide authenticity is part of the risk.
Use-case scores
0–10 against the evidence we have, not a gym ranking. Hidden domains do not apply here.
- Longevity / aging2/10
Baar 2017 (PMID 28340339) mouse senolytic. mg/kg in mice is not a 10 mg vial protocol. Mechanism band.
Compound card
- Class
- D-retro-inverso FOXO4/p53 interfering peptide (senolytic research)
- Formula
- D-retro-inverso peptide (custom synthesis)
- Status
- Not FDA-approved · research use
How it works
FOXO4-DRI is a D-retro-inverso (DRI) peptide that selectively induces apoptosis (programmed cell death) in senescent cells while leaving healthy cells unharmed. It is the first rationally designed peptide-based senolytic.
In senescent cells, the FOXO4 transcription factor binds and sequesters p53 in the cytoplasm, preventing p53 from entering the nucleus and triggering apoptosis. Senescent cells are otherwise resistant to normal cell death despite accumulating DNA damage. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, freeing p53 to translocate to the nucleus and activate apoptotic gene programs. The D-retro-inverso (mirror amino acid) design makes it resistant to protease degradation, enabling systemic activity.
In mouse studies, FOXO4-DRI reversed aging phenotypes including fur loss/discoloration, renal dysfunction, and physical frailty. Liver senescent cell burden was reduced significantly after just 3 doses. This is a landmark proof-of-concept for senolytic peptide therapy.
Source: PMID: 28340339
Background & History
FOXO4-DRI is a D-amino acid retro-inverso peptide designed to disrupt the interaction between FOXO4 and p53 inside senescent cells. Developed by Peter de Keizer at the Princess Máxima Center (Netherlands), it was published in Cell (2017) showing it selectively induced apoptosis in senescent cells - the first demonstration that targeted senolysis with a peptide was achievable. This landmark paper established FOXO4-DRI as a potentially transformative longevity compound. It specifically kills senescent cells (which drive aging via SASP) while leaving normal cells unaffected.
Research Use Cases
- ✓Identity: Baar 2017 mouse senolytic vs a gray-market D-peptide
- ✓Do not scale mouse mg/kg onto a human
- ✓Not a frailty or cancer protocol on this site
Dosing
| Phase | Dose | Frequency | Notes |
|---|---|---|---|
| Mouse-Derived Protocol (Human Translation) | 5 mg/kg | Every 3 days for 3 doses (SC or IP) | Based on the published mouse protocol. Human translation is experimental. Very limited human data. Consult a longevity physician before use. |
Administration
Timeline
Who it is for
Senolytic / Cellular Rejuvenation
LowMost targeted senolytic peptide known. Proof-of-concept in mice is compelling, but human data is very limited.
Longevity Research
LowRepresents a new class of aging intervention. Suitable only for experimental longevity research use.
Reconstitution
| Vial | Water | Concentration | Example dose |
|---|---|---|---|
| 10 mg lyophilized | 2 mL BAC | 5 mg/mL | 10 mg / 2 mL = 5 mg/mL. Mouse mg/kg is not a human example dose. Authenticate the D-peptide. |
Change vial size or water volume? Open the reconstitution calculator.
Safety & Considerations
Research peptide with very limited human data. Initial mouse studies are promising but not equivalent to human safety data. May cause transient inflammation as senescent cells are cleared. Not recommended for cancer patients. Very expensive custom synthesis. Completely experimental - use only under physician supervision.
Regulatory & Legal Status
Not currently on the WADA 2026 Prohibited List. Policies may change - verify before competition.
Research Chemical
US Compounding: Not eligible / not available
⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.
Limits of current evidence
- Do not scale 5–20 mg/kg mouse doses onto a 70 kg human as if that were a protocol.
- This site will not treat aging or cancer from a FOXO4 page.
Verdict
FOXO4-DRI is an experimental senolytic peptide from mouse work. It is not a frailty drug. Killing senescent cells in mice is not a human anti-aging NDA. Cost and authenticity of gray-market D-peptides are part of the risk.
Interactions & Contraindications
Experimental compound - very limited human data. Induces apoptosis specifically in p21-positive senescent cells. Theoretical concern: some senescent cells serve protective roles (wound healing senescence, placental cells) - unknown impact with repeated dosing. Use infrequently (quarterly cycles per de Keizer protocol).
Synergies & Common Stacks
FOXO4-DRI clears existing senescent cells; Epitalon activates telomerase to prevent cells from becoming senescent via telomere erosion. Sequential senolytic + senomorphic protocol.
FOXO4-DRI removes senescent cells; NAD+ supports the healthy cells that replace them through SIRT1 and DNA repair mechanisms.
Appears in goal guides
Goal guides are maps, not clinic protocols. A mention here is not a treatment plan.
Frequently Asked Questions
How does FOXO4-DRI kill senescent cells?▼
What is the FOXO4-DRI protocol?▼
References
- Baar MP, Brandt RMC, Putavet DA, Klein JDD, de Keizer PLJ et al. “"Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis".” Cell (2017). PMID: 28340339
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