The experimental senolytic peptide — disrupts FOXO4-p53 binding in senescent cells to trigger their apoptosis. Real mechanism, mouse data, practically no human clinical data.
FOXO4-DRI (also called FOXO4-D-retro-inverso) is a synthetic peptide engineered by Peter de Keizer’s group at Erasmus Medical Center. It’s a D-amino-acid retro-inverso analog of a 37-amino-acid fragment of FOXO4 — designed to interrupt the FOXO4-p53 interaction that keeps senescent cells alive.
The 2017 Cell paper (Baar et al.) is the foundational publication. In naturally aged mice, FOXO4-DRI selectively killed senescent cells and restored fur density, fitness, and kidney function. Since then: significant preclinical development; essentially zero published human clinical data.
Not FDA approved. No published human trials. Research chemical only. Not WADA prohibited.
Senescent cells survive despite accumulating damage partly because FOXO4 binds and sequesters p53 in the nucleus, preventing p53 from triggering apoptosis. FOXO4-DRI disrupts this binding, releasing p53 to execute the senescent cell — while leaving healthy cells unaffected.
The D-isoform stereochemistry makes the peptide resistant to protease degradation, giving it a meaningful in-vivo half-life despite being a peptide.
The target has since been characterised structurally. Bourgeois 2025 (Nat Commun, PMID 40593617) used NMR to show FOXO4-DRI binds the disordered transactivation domain of p53, forming a transiently folded complex — and found that both the FOXO4-derived region and the cationic cell-permeability peptide contribute to the interaction. The delivery moiety is not inert, which matters for anyone assuming a vendor’s sequence variant behaves identically.
Healthy cells have lower FOXO4-p53 levels, so FOXO4-DRI doesn’t trigger apoptosis in them. This is what distinguishes senolytics from general cytotoxic drugs.
| Benefit | Evidence |
|---|---|
| Senescent cell clearance (mouse) | Baar 2017 (Cell, PMID 28340339) identified FOXO4 as the pivot keeping senescent cells alive, then designed a peptide to perturb the FOXO4–p53 interaction. In senescent cells this caused p53 nuclear exclusion and cell-intrinsic apoptosis, selectively |
| Functional improvements (mouse) | In the same paper: restored fitness, fur density and renal function in both fast-ageing XpdTTD/TTD mice and naturally aged mice — the results that made this compound famous |
| Post-chemo recovery (mouse) | Baar 2017 also showed the peptide neutralised doxorubicin-induced chemotoxicity under conditions where it was well tolerated in vivo |
| Human data | Still none. Re-checked against PubMed — no human clinical trial of FOXO4-DRI has been published. The most recent overview (Alameen 2026, PMID 42024235) surveys brain-ageing applications entirely in aged mammalian models |
The mouse results are striking. The absence of human data is striking in the other direction. This is firmly in the "promising but unproven" category — treat accordingly.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeNot medical advice. These figures describe what is reported in the literature and what practitioners and communities do — not a recommendation, and for most compounds here no human dose-finding study exists. Talk to a qualified healthcare provider.
The "1 mg/kg" figure commonly passed around in senolytic circles comes directly from mouse dosing in Baar et al. (2017). Scaling a rodent dose to a 68 kg human by body weight alone is not how pharmacology works — species differ in metabolism, protein binding, receptor density, and clearance by orders of magnitude. A simple body-weight extrapolation to tens-of-milligrams human doses may be a dangerous overestimate and could plausibly underestimate systemic effects and toxicity.
There is no published human PK, safety, or dose-finding data. No defensible "correct" human dose exists. The community-circulated 1–5 mg/kg numbers should be read as "the only numbers around," not as validated doses.
Treat any use of FOXO4-DRI as experimental self-research. If you proceed, start at the lowest end of the range with medical supervision.
Not medical advice. These figures describe what is reported in the literature and what practitioners and communities do — not a recommendation, and for most compounds here no human dose-finding study exists. Talk to a qualified healthcare provider.
10 mg vial + 2 mL BAC water = 5 mg/mL. For a 150-lb person at 1 mg/kg (~68 kg), that’s 68 mg — more than one vial per dose.
Pre-filled with a typical FOXO4-DRI setup. Edit any field — the draw updates live.
Insulin syringe — 100 units = 1 mL
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The items below are anecdotal from self-experimenters, not findings from controlled human trials. The published FOXO4-DRI abstracts are exclusively preclinical (mouse models, in vitro).
FOXO4-DRI is a research peptide not approved by the FDA for human use. It is sold only as a research chemical, and StackTrax does not endorse or facilitate personal use.
Quality varies enormously among research-chemical suppliers. At minimum, look for:
Lyvn does not carry FOXO4-DRI. They are the vendor we recommend elsewhere on this site, and they publish the full independent panel per batch — which makes their catalogue a useful yardstick for the criteria above even on a compound they do not stock. We are not recommending a specific supplier for FOXO4-DRI itself, because we have no basis to.
For research use only. Not for human consumption. 21+.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeFOXO4-DRI (also called FOXO4 D-retro-inverso) is a synthetic peptide engineered by the de Keizer lab at Erasmus Medical Center. It is a D-amino-acid retro-inverso analog of a 37-amino-acid fragment of FOXO4, designed to interrupt the FOXO4-p53 interaction that keeps senescent cells alive. The D-isoform stereochemistry makes it resistant to protease degradation, giving meaningful in-vivo half-life for a peptide.
Mechanistically, yes. Senescent cells survive partly because FOXO4 binds and sequesters p53 in the nucleus, blocking apoptosis. FOXO4-DRI disrupts that binding so p53 can execute the senescent cell, while healthy cells (which have lower FOXO4-p53 levels) are largely spared. In naturally aged mice (Baar 2017, Cell), it restored fur density, running capacity, and kidney function.
Virtually none. The published FOXO4-DRI literature is exclusively preclinical (mouse models and in vitro work). There are only small open-label case reports and anecdotal biohacker self-experiments. No human PK, no safety trials, no efficacy data. It is firmly in the "promising but unproven" category.
Community protocols run 1 to 5 mg/kg weight-based, given weekly for 3 consecutive weeks, SubQ or IV. Those numbers come directly from mouse dosing in Baar et al. (2017). Scaling a rodent dose to humans by body weight alone is not how pharmacology works, and a simple extrapolation to tens of milligrams per dose may be a dangerous overestimate. No defensible human dose exists; treat any use as experimental N=1 self-research.
Reported anecdotally (not from controlled trials): transient fatigue and flu-like symptoms during or after a senolytic burst, injection site reactions, and mild nausea. The theoretical concern is mass senescent-cell apoptosis releasing SASP inflammatory cytokines, which could trigger a systemic inflammatory response. That is plausible from the mechanism, not observed in a controlled human setting.
Dasatinib plus Quercetin (D+Q) is the better-studied senolytic stack with more human clinical trial data behind it (small Phase 1/2 trials in idiopathic pulmonary fibrosis and diabetic kidney disease). FOXO4-DRI has more striking mouse data but essentially no human data. The cancer interaction with FOXO4-DRI is also context-dependent rather than uniformly avoid: PMID 34877934 shows it can radiosensitize NSCLC tumors. Still, no human oncology safety data exist, and you should avoid it outside of a research context.
Disclaimer: This guide is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. The compounds discussed are not FDA approved for human use. Always consult a qualified healthcare provider before starting any new supplement or peptide protocol. StackTrax does not sell peptides or supplements directly — purchase links go to third-party vendors. StackTrax is not responsible for the products, quality, or business practices of any third-party vendor.
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StackTrax guides cover peptides and compounds that are not FDA-approved for the uses discussed. The dosing, reconstitution, and safety information is compiled from published research and community protocols for educational purposes only.
Before using any compound mentioned here, consult a qualified healthcare provider. StackTrax does not sell, prescribe, or recommend these substances for personal use.