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.
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: selective elimination of senescent cells in naturally aged mice |
| Functional improvements (mouse) | Restored fur density, running capacity, and kidney function in aged mice |
| Post-chemo recovery (mouse) | Reduced chemotherapy-induced senescence and its long-term consequences |
| Human data | Virtually none — small open-label case reports, anecdotal biohacker self-experiments |
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 FreeThe "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.
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:
StackTrax’s preferred partner NextGen Peptides does not currently carry FOXO4-DRIin their catalog, which is why you don’t see a direct purchase link here. Other major research-chemical suppliers carry it; we don’t specifically recommend one for this compound.
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.
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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.
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