FOXO4-DRI
Anti-Aging
In short
- A designed senolytic peptide intended to selectively kill senescent cells by disrupting the FOXO4-p53 interaction.
- The 2017 mouse study behind it is genuinely striking — restored fitness, fur density, and renal function in aged and progeroid mice.
- "DRI" means D-retro-inverso: built from D-amino acids in reverse sequence, which makes it resistant to proteolysis.
- No human trial has been conducted, and senolytics as a class remain unproven in humans.
- The mechanism is deliberate induction of apoptosis, which is a fundamentally different risk category from most compounds here.
Structure
How it works
Senescent cells accumulate with age. They stop dividing but do not die, and secrete inflammatory factors — the senescence-associated secretory phenotype — that drive tissue dysfunction.
Senescent cells survive partly by sequestering p53 in the nucleus via FOXO4, preventing p53 from triggering apoptosis. FOXO4-DRI is a peptide that competes with that interaction, releasing p53 and allowing the senescent cell to undergo apoptosis.
The D-retro-inverso design — D-amino acids assembled in reverse — preserves the side-chain topology needed for binding while making the peptide essentially invisible to proteases.
What the research shows
The 2017 Cell paper by Baar and colleagues reported that FOXO4-DRI selectively induced apoptosis in senescent cells and, in aged and progeroid mice, restored fur density, renal function, and fitness.
That result attracted enormous attention and is the entire basis for the compound's reputation.
No human study has been conducted. No senolytic has yet demonstrated clinical benefit in a completed human trial, though dasatinib plus quercetin and other candidates are in trials.
Dosing in the literature
Figures below are quoted from published studies, with the species or population they were measured in. They are records of what was studied, not recommendations.
| Studied in | Amount | Route | Source |
|---|---|---|---|
| Mouse — senolytic study (Baar et al. 2017) | Approximately 5 mg/kg, three doses per cycle, cycles repeated | intraperitoneal or intravenous | PubMed |
Commonly reported ranges
These are amounts people report using. They are not from any study, have not been evaluated for safety, and are reproduced here only because they circulate widely and are better seen alongside the evidence than instead of it.
| Reported by | Amount | Route |
|---|---|---|
| Commonly reported, in short intermittent cycles | 5–10 mg per dose, a few doses per cycle | subcutaneous |
No published human pharmacokinetic study establishes a dose, interval, or duration for this compound. Community figures below have no trial behind them and are reports of practice, not evidence. Intermittent cycling rather than continuous dosing is the pattern in both the mouse study and community use — the senolytic rationale is to clear accumulated cells periodically, not to maintain constant exposure. Nothing about human dose, cycle length, or frequency has been established.
Handling and storage
Supplied as a lyophilised powder requiring reconstitution with bacteriostatic water. The powder is comparatively stable; once reconstituted it is refrigerated and used within weeks. Track the date you reconstitute each vial — the Inventory section does this, and it is the difference between knowing a vial is three weeks old and guessing.
Subcutaneous injection in short intermittent cycles is the community pattern. The mouse study used intraperitoneal and intravenous routes.
As a D-amino acid peptide it is unusually protease-resistant, which affects its persistence but not its stability in solution.
Side effects
No human safety data exists.
The mouse study reported the peptide was tolerated at the doses used and did not cause the neutropenia seen with some senolytic approaches.
The mechanistic concern is specific and serious: this compound works by releasing p53 to trigger apoptosis. Selectivity for senescent cells depends entirely on the FOXO4-p53 interaction being a senescence-specific vulnerability. If selectivity is incomplete in humans, the mechanism kills cells you need. That is a categorically different risk from a compound that modulates a receptor.
Senolytic clearance also transiently increases the burden of apoptotic debris, which is why cycling rather than continuous dosing is the described approach.
Combinations
No interaction data. Combining with other senolytics (dasatinib, quercetin, fisetin) targets the same process by different mechanisms and compounds an unstudied intervention.
Research status
The Baar et al. 2017 Cell paper is genuine, high-profile, well-conducted mouse work from Peter de Keizer's group.
The senolytics field is legitimate and active. What has not happened is translation: no senolytic has completed a trial demonstrating clinical benefit in humans, and FOXO4-DRI specifically has never been given to a person under study.
Legal status
Not approved in any jurisdiction. Sold for research use only.
WADA status
Not specifically named on the Prohibited List. Falls under WADA class S0, which prohibits any pharmacological substance not currently approved by any governmental regulatory health authority for human therapeutic use. Treat it as prohibited in sport.
Conclusion
FOXO4-DRI rests on one striking mouse paper and a mechanism that works by deliberately triggering cell death.
That mechanism is what makes it interesting and what makes it different in kind from everything else here. Selectivity is the entire safety argument, and selectivity in mice is not selectivity in humans — which nobody has tested.
Sources
Track your own FOXO4-DRI protocol
Peppers logs your doses, models your levels from this half-life, tracks your vials and tells you when you will run out. Free on iPhone.
Reference and educational information only. Not medical advice. Nothing here diagnoses, treats, or prescribes, and nothing here is a recommendation to use any compound. The compounds described are research chemicals and are not approved for human consumption. Legal and anti-doping status change — the review date above is when these claims were last checked. Talk to a qualified clinician about anything you intend to take.