FOXO4-DRI: uses, evidence and status

compound file

The answer, first. A cell-penetrating peptide built from D-amino acids in reverse order, designed at Erasmus MC in 2017 to break the FOXO4-p53 interaction inside senescent cells. The strongest evidence is for clearing senescent cells, graded D — animal or mechanism only.

The peptide drives p53 out of the nucleus and triggers apoptosis selectively in senescent cells, and cleared senescent human chondrocytes from expanded cultures ¹⁴.

Mice and cell culture. No human has been dosed. Every other use — organ function in aged animals, chemotherapy toxicity, brain aging and cognition — grade D or E: animal or mechanism data with no controlled human outcome.

What it is used for

Every use graded on its own evidence, not the compound as a whole. 4 outcomes, ranked by what the human record supports.

#outcome · human · animal · gradewhat the best evidence actually shows

01Clearing senescent cellsno trial · mice plus human cells in culturegrade DThe peptide drives p53 out of the nucleus and triggers apoptosis selectively in senescent cells, and cleared senescent human chondrocytes from expanded cultures ¹⁴. Mice and cell culture. No human has been dosed.

02Organ function in aged animalsno trial · aged and progeroid micegrade DAt 5 mg/kg three times on alternate days, naturally aged mice showed lower plasma urea and creatinine, restored fur density and improved running-wheel activity ¹. Groups of seven to eight. Mouse data only.

03Chemotherapy toxicityno trial · doxorubicin model in micegrade DThe peptide neutralised doxorubicin-induced liver toxicity and weight loss in mice, which is the experiment it was designed to pass ¹. No human chemotoxicity study has used it.

04Brain aging and cognitionno trial · aged rodent modelsgrade DA 2026 review collects aged-rodent results in which the peptide restored cerebral blood flow and blood-brain barrier integrity and improved memory ⁷. Review of rodent work. The human senolytic data it cites is for fisetin, a different compound.

gradewhat it means

ARegulatory approval, or multiple adequately-powered trials agreeing with each other

BAt least one well-powered human randomised trial, with the direction replicated

CSmall or open-label human trials only

DAnimal or mechanism data only, with no controlled human outcome

EA claim the human trials have already killed

How it works

The proposed mechanism, in three steps. A mechanism is a reason to run a trial, never a substitute for one.

1targetIn senescent cells FOXO4 holds p53 in the nucleus. The peptide is a decoy that occupies the disordered p53 transactivation domain ¹².

2signalp53 is excluded from the nucleus, and the senescent cell loses the block that was keeping it out of apoptosis ¹.

3effectSenescent cells die and surrounding tissue recovers function in mice, while non-senescent cells are reported to be spared ¹.

What it does not do

Claims the current record does not support. Worth knowing before you set expectations.

not supported by the evidence

FOXO4-DRI reverses aging in people. No human has been given this peptide in any published or registered study. The record is mice and cells in a dish ¹⁴⁵.
Clearing senescent cells is always good. In mice, removing senescent cells worsened pulmonary hypertension, raising right ventricular pressure and vessel remodelling ³. Senolysis carries directional risk.
Senolytics already have human results. Dasatinib with quercetin has a 14-patient open-label pilot in pulmonary fibrosis ⁶. Different drug class, uncontrolled, and not this peptide.
The mouse dose scales to a person. No pharmacokinetic, absorption or immunogenicity data exists for this peptide in humans, and it is a large D-amino-acid construct ¹.

How it is used

What published protocols administered, and what the community reports doing. Descriptive on both counts, and never a recommendation.

routeSubcutaneous injection in practice. The founding mouse work used intravenous and intraperitoneal injection, never subcutaneous ¹.

formatLyophilised powder in vials, reconstituted with bacteriostatic water.

published dosesThere is no human dose. The founding study gave mice 5 mg/kg intravenously or intraperitoneally, three times on alternate days, and repeated that cycle ¹. Nothing has been published on how, or whether, that translates to a person of any weight.

human pharmacokineticsNo human pharmacokinetic data published.

reported conventionsAs reported on longevity forums, 2019-2026: short pulses of a few consecutive days, spaced weeks or months apart. That echoes the mouse cycle rather than any human protocol. Report volume is very low. Convention, not guidance.

commonly paired withEpithalon NAD+

This site does not publish protocols to follow. The doses above are what studies administered or what users report, stated as facts about the literature and the market. How protocols are structured, mixing and storage and the reconstitution calculator cover the arithmetic.

What to expect

Where a trial measured it, the trial. Where only the community reports it, that is said out loud.

onsetNo study measured onset in any species against a clinical endpoint. In mice, renal markers and fur density changed over weeks of repeated cycles ¹. As reported: nothing consistent, and the report volume is too low to describe a pattern.

most common reportAs reported: no perceptible effect, with occasional flu-like malaise in the day after a dose. The reports are few.

adverse effectsNo trial has published adverse event rates. The peptide's own literature carries a warning: in mice, clearing senescent cells made pulmonary hypertension worse ³. As reported: injection site reactions and short-lived malaise.

the stop signalAs reported: people stop at the end of a self-imposed pulse. No published stopping rule, no marker, and no way to tell whether anything was cleared.

Approval and status

What regulators and sport bodies have actually said, separately from what the evidence shows.

approvalNot approved anywhere. Sold as a research chemical.

FDANot named on FDA's compounding risk list. No registered clinical trial of this peptide exists in any phase.

sport [WADA]Not named on the List. Caught by S0, non-approved substances.

sold asresearch chemical

Check the vial

The grade above describes a molecule studied under controlled conditions. It says nothing about the powder in a particular vial.

That gap is the one part of this market a reader can actually close. How to read a certificate of analysis covers the five measures in five minutes, and the 2026 audit grades vendors on the documents they publish against a rubric printed in full.

Questions we get

What is FOXO4-DRI used for?

On the human record, nothing. It is sold as a senolytic, to clear senescent cells. The support is one 2017 mouse and cell paper ¹.

After 5 mg/kg three times on alternate days, aged mice showed lower plasma urea and creatinine, restored fur density and better running-wheel activity. No human has been dosed in any published study.

How is FOXO4-DRI used?

Descriptively, and not as guidance: subcutaneous injection from a reconstituted vial, in short pulses of a few days spaced weeks or months apart. That pattern imitates the mouse cycle and comes from a very small body of forum reports.

The published dosing is mouse only, 5 mg/kg intravenously or intraperitoneally, three times on alternate days ¹.

How long does FOXO4-DRI take to work?

No study has measured that in any species against a clinical endpoint. In mice, kidney markers and fur density shifted over weeks of repeated cycles ¹. There is no human timescale, no marker a person could follow, and no way to confirm from the outside whether any senescent cell was cleared.

Has FOXO4-DRI been tested in humans?

No. There is no registered clinical trial and no published human dosing of any kind. The evidence is one 2017 mouse and cell paper ¹, follow-up cell work in human chondrocytes and keloid fibroblasts ⁴⁵, and a mechanistic structure paper ².

Human senolytic data exists only for a different class: dasatinib with quercetin, in a 14-patient open-label pilot ⁶.

Is clearing senescent cells safe?

Not established, and one result argues against assuming it. In mice, clearing senescent cells by three separate methods, this peptide among them, made pulmonary hypertension worse ³. Higher right ventricular pressure, more hypertrophy, more vessel remodelling. Senescent cells do jobs as well as damage, and no human study has weighed that trade.

References

Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell. 2017;169:132-147. PMID 28340339
Bourgeois B, Sperl LE, Zacharias M, Madl T. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun. 2025;16:5672. PMID 40593617
Born E, Lipskaia L, Breau M, et al. Eliminating senescent cells can promote pulmonary hypertension development and progression. Circulation. 2023;147:650-666. PMID 36515093
Huang Y, Zhang L, Wang J, et al. Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes. Front Bioeng Biotechnol. 2021;9:677576. PMID 33996787
Kong YX, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Commun Biol. 2025;8:299. PMID 39994346
Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-563. PMID 30616998
Alameen AAM, et al. Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline. Naunyn Schmiedebergs Arch Pharmacol. 2026;399:14659-14676. Review. PMID 42024235

Inside Your Peptides is published by the owners of the next lab, a vendor graded elsewhere on this site. We sell nothing here, and this page carries no vendor link. Grades follow the published criteria in our editorial policy — never referral terms. Research and education only. Not medical advice.