FOXO4-DRI is the most expensive peptide per milligram on many research price lists and the one with the thinnest dose record. It exists because of one 2017 paper, it has been given to mice in one regimen, and it has never been given to a person in a registered trial. This page sets out exactly what the published record contains — which is short enough to state in full.
What it is
In March 2017, a group led by Peter de Keizer at Erasmus University Medical Center published in Cell (Baar et al., PMID 28340339) that senescent cells — damaged cells that stop dividing but do not die — rely on the protein FOXO4 holding p53 in the nucleus to stay alive. They designed a peptide to break that interaction. In senescent cells it "selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis", in the abstract's words, while normal cells were largely spared. The "DRI" is D-retro-inverso: the sequence is built from mirror-image D-amino acids in reversed order, which keeps the side chains in a similar arrangement while making the peptide harder for enzymes to digest. That is the whole basis of the "senolytic peptide" sold today.
Every in-vivo dose in the record
| Source | Animal | Dose | Schedule | What was measured |
|---|---|---|---|---|
| Baar et al., Cell 2017 | chemotherapy-treated mice | 5 mg/kg, intraperitoneal | days 1, 3, 5 | liver toxicity, weight loss |
| Baar et al., Cell 2017 | fast-ageing Xpd TTD/TTD and naturally aged mice | 5 mg/kg, intraperitoneal | every other day ×3 | fur, fitness, kidney markers at 30 days |
| Zhang et al., Aging 2020 | naturally aged male mice (20–24 months) | 5 mg/kg, intraperitoneal | every other day ×3 | serum testosterone at 30 days |
The cell experiments in the 2017 paper used 25 µM. The 2020 study, on senescent Leydig cells in the testes (PMID 31959736), is the one most often cited for testosterone claims, and it repeats the original regimen rather than testing a new one.
Three features of that regimen matter more than the number. The route was intraperitoneal — into the abdominal cavity, standard in mouse work — not under the skin. The course was three doses, not a continuing protocol. And the animals were then followed for about a month, because the aim was to clear a population of cells once and watch tissue recover.
Why 5 mg/kg is not a human figure
Multiplying 5 mg/kg by a 70 kg body gives 350 mg, and that number is wrong in a specific way: doses do not scale with body weight between species. The standard conversion, set out in a widely used practice guide (Nair and Jacob, 2016), divides by species factors based on body-surface area, and it exists to estimate a cautious starting dose for a first human trial, after toxicology in animals — with a further tenfold safety margin. For FOXO4-DRI, neither the toxicology package nor the first trial exists. Any human milligram figure attached to it, including the ones on vendor and forum pages, is an extrapolation nobody has tested. Our page on reading a dosing claim covers how to tell a tested figure from a derived one.
The size of the literature
| Record | Count, 2026-09-28 |
|---|---|
| PubMed records containing "FOXO4-DRI" | 19 |
| …of which human trials | 0 |
| ClinicalTrials.gov studies of FOXO4-DRI | 0 |
The 19 records are cell and animal studies — keloid fibroblasts, cartilage cells grown in the lab, lung fibrosis and radiation injury in mice, ageing testes — and reviews. The founding 2017 paper is not among them: its abstract never uses the name, calling it "a FOXO4 peptide", so a literal search misses the source of the regimen the others repeat. A 2025 Nature Communications paper refined the mechanism, reporting that FOXO4 and FOXO4-DRI bind the disordered transactivation domain of p53.
The finding that cuts the other way
Clearing senescent cells is not uniformly helpful. In 2023, Born and colleagues in Circulation studied senescent cells in pulmonary hypertension, using a genetic "suicide gene" model and senolytic drugs including ABT263 and FOXO4-DRI. Their title states the conclusion: "Eliminating senescent cells can promote pulmonary hypertension development and progression." In their mouse models, removing senescent cells raised pressure in the lung circulation and increased vessel remodelling, and the lung's endothelial cells — a large share of its senescent cells — were lost. It is animal work, but it is the clearest published signal that a senolytic can make a condition worse, and it is absent from most pages selling the peptide.
What a vial represents
On 2026-09-28 one research-chemical store that publishes its catalogue prices listed FOXO4-DRI, 10 mg, at $342.40 — $34.24 per milligram, several times the per-milligram prices in our peptide price survey. The arithmetic of the only published regimen:
| Figure | |
|---|---|
| Mouse body weight (typical adult) | 30 g |
| Dose per injection at 5 mg/kg | 0.15 mg |
| Full three-dose course | 0.45 mg |
| Mouse injections in one 10 mg vial | about 66 |
That is what the milligram figure on the vial corresponds to in the only setting where the peptide has been dosed. It says nothing about the vial's actual contents, which are unverified — the reason our research-use-only page exists — and nothing about a human dose, which the record does not contain.
What is not known
- Any dose, schedule, route or safety profile in humans.
- Whether subcutaneous injection, the route used with research vials, delivers the peptide to senescent cells the way intraperitoneal injection did in mice.
- The effect of repeated courses, which no study has tested.
- Whether the benefits seen in mice — fur, fitness, kidney markers, testosterone — occur in people at all.
Anyone considering FOXO4-DRI is considering an unregistered experiment on themselves; the decision belongs with a physician who can see the whole record. Other longevity peptides with similarly thin files are on our epitalon dosage page and the peptide dosage chart.
Sources and dates
- Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017;169(1):132-147. PMID 28340339; full text PMC5556182 (methods and figure legends: 5 mg/kg i.p., days 1, 3, 5; 25 µM in vitro). Read 2026-09-28.
- Zhang C, Xie Y, Chen H, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020;12(2):1272-1284. PMID 31959736; full text PMC7053614. Read 2026-09-28.
- Born E, Lipskaia L, Breau M, et al. Eliminating senescent cells can promote pulmonary hypertension development and progression. Circulation. 2023;147(8):650-666. PMID 36515093. Abstract read 2026-09-28.
- Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7(2):27-31. PMC4804402. Read 2026-09-28.
- PubMed search "FOXO4-DRI" (19 records) and ClinicalTrials.gov search "FOXO4" (1 unrelated study), 2026-09-28.
- Public WooCommerce catalogue endpoint of one research-chemical store, searched for "foxo4", 2026-09-28. List price, not a verified purchase.
