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RUO · Research Use Only⚠ One-paper compound+2 more

FOXO4-DRI

A **29-amino-acid** D-retro-inverso peptide designed to selectively kill senescent cells by disrupting the FOXO4-p53 interaction. We read all 17 studies. The protocol is below.

Updated 03 May 2026Read 10 minEvidence ●○○○○Citations 17
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The FOXO4-DRI Report · $19

Everything you need to start: dose, sourcing, safety, our verdict.

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Built from 17 cited studies.

Status
Research-only
Class
One-paper compound
Evidence
1/ 5●○○○○
Peptide length
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Originating lab
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Source paper
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⚠ One-paper compound
Read this if
  • **top-of-page fork — the studied population is aged mice.** Baar et al. Cell 2017 (Peter de Keizer's group at Erasmus Medical Center) showed rejuvenation in 18–24-month-old mice on a 3-week regimen. There is no human trial data. If you came expecting a human-trial backbone, there isn't one — read the rest of the page through that frame
  • you're in the Bryan Johnson "Don't Die" orbit and senolytics is the next frontier for you
  • you've read the de Keizer 2017 paper and want to know if anyone has reproduced it
  • the 24–72 hour flu-like reaction post-dose intrigues you rather than scares you
Skip this if
  • **you have a personal or family cancer history** — FOXO4-DRI is a senolytic; killing senescent cells is theoretically anti-cancer in mice but the mechanism (a D-retro-inverso peptide disrupting the FOXO4-p53 interaction) is not well-characterized in humans. Cancer-history users should not self-direct this molecule
  • you want more than one paper of human-relevant data — there's effectively one
  • you have active malignancy or recent autoimmune flares
  • you're not okay with a compound that has no published toxicology in healthy adults
The 4 ways you can buy FOXO4-DRI
Brand
✗
Not available
No FDA-approved FOXO4-DRI exists.
Compounded 503A
✓
Off-label
$400–$800/mo where sold
Compounders shipping a deliberately-cytotoxic peptide pre-trial are legally and ethically exposed.
RUO (research-only)
✓
Sold 'for research only'
$150–$400/mo
D-retro-inverso synthesis is hard, sub-90% purity is common; identity by mass spec alone is insuff…
Gray market
✓
Unregulated overseas import
~$38/mo
Crypto/Wise pay; D-retro-inverso stereochemistry verification is even harder for gray vendors than…
Click any lane for the full Sourcing breakdown.
First 90 days · FOXO4-DRI
Weeks 1–2
Pulsed protocol, NOT a daily peptide. The Baar 2017 Cell mouse paper used 3 doses over 3 days, then a wash-out — that's the only published protocol. Anyone selling 'daily FOXO4-DRI' is extrapolating from rodent work that explicitly did not test daily dosing in humans.
Weeks 4–8
Wash-out window. If the senescent-cell-clearance hypothesis works (it has not been tested in humans), the mouse data suggests effects emerge over 3–10 weeks post-treatment. There is no human PK to validate the timing. Track subjective recovery, sleep, joint stiffness — but those are not specific senolytic readouts.
Week 12 — decide
Honest decision point. The mouse paper's measurable outcomes (fitness markers, renal function, fur density) don't have direct human analogs. You're trial-of-one'ing an animal-only senolytic — accept that or stop.
Quit if
  • Personal or first-degree-relative history of cancer — p53 derepression is the senolytic mechanism AND the chemotherapy mechanism; uncharacterized interaction.
  • Acute symptoms within hours of dose — there is no published human safety profile; treat any unexpected systemic signal as a stop.
  • Tempted to dose daily or weekly — the published protocol is pulsed (3 doses, washout, repeat periodically). Daily dosing is gym-bro extrapolation.
  • Active chemotherapy or radiation — p53-axis interaction is theoretically real and direction-uncertain; do not stack mid-treatment.
Identity

What it is.

FOXO4-DRI is a synthetic designed to kill senescent cells — the so-called "zombie cells" that accumulate with age, refuse to die, and pump out inflammatory signals that damage the tissue around them. Senescent cells express a stress program that depends on the interaction between two proteins, FOXO4 and p53. The peptide is engineered to disrupt that interaction, which tips the cell into apoptosis.

It was developed by Peter de Keizer's group at Erasmus and published in *Cell* in 2017. The mouse work — old, naturally aged mice given the showed restored kidney function, regrew fur, and ran further on a treadmill — is one of the most-shared longevity papers of the past decade.

There is no version. There is no human trial. It is sold strictly as a research chemical (RUO), often by vendors who are at the more aggressive end of the longevity- market.

TL;DR

TL;DR. 30-second version.

The compressed verdict — what FOXO4-DRI actually is, what the human evidence shows, and the watch-for in three bullets. Locked.

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Mechanism

Mechanism.

Mechanism · in the FOXO4-DRI report

How the molecule actually works — receptor profile, downstream signaling, what to expect mechanistically.

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Evidence

Evidence. What we actually know in humans.

Evidence · in the FOXO4-DRI report

The trial breakdown — phase, n, primary endpoint, who funded, what hit, what didn't.

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Human-Evidence Factbox
Peptide length
$19 ↓
Originating lab
$19 ↓
Source paper
$19 ↓
Human trials
$19 ↓
Independent replications (mouse)
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Mechanism
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Half-life
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WADA status
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Long-term safety data
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Dose

Dose. The actual protocol.

Dose · in the FOXO4-DRI report

The specific protocol — dose, titration schedule, cycle pattern, frequency, route.

We read 17 studies to write this report.
Get the report · $19 ↓
Sourcing

Sourcing. Where the cohort actually buys.

Sourcing · in the FOXO4-DRI report

Sourcing breakdown — vendor methodology, red flags, our published test results, COA checklist.

We read 17 studies to write this report.
Get the report · $19 ↓
Safety

Safety. Side effects.

Safety · in the FOXO4-DRI report

The watch-for list — contraindications, drug interactions, monitoring labs, when to stop.

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Editorial Position

Editorial position.

Editorial Position · in the FOXO4-DRI report

Our editorial position — explicit yes / no / depends, with the reasoning behind it.

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Citations

Citations.

  1. 01Born E, et al. Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. Circulation. 2023;147(8):650-666. PMID: 36515093.
  2. 02Liu Y, et al. FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice. Naunyn-Schmiedeberg's archives of pharmacology. 2023;396(10):2393-2403. PMID: 37074394.
  3. 03Meng J, et al. Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis. JCI insight. 2021;6(23). PMID: 34877934.
  4. 04Bourgeois B, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nature communications. 2025;16(1):5672. PMID: 40593617.
  5. 05Kong YX, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Communications biology. 2025;8(1):299. PMID: 39994346.
+Show all 17 citations
  1. 06Alameen 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-Schmiedeberg's archives of pharmacology. 2026. PMID: 42024235.
  2. 07Li Y, et al. FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells. Experimental gerontology. 2024;195:112522. PMID: 39025385.
  3. 08Zhang C, et al. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging. 2020;12(2):1272-1284. PMID: 31959736.
  4. 09Hu Z, et al. FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway. Frontiers in bioengineering and biotechnology. 2026;13:1729166. PMID: 41625068.
  5. 10Huang Y, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Frontiers in bioengineering and biotechnology. 2021;9:677576. PMID: 33996787.
  6. 11Han X, et al. FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway. Journal of cellular and molecular medicine. 2022;26(11):3269-3280. PMID: 35510614.
  7. 12Valentijn FA, et al. Cellular senescence in the aging and diseased kidney. Journal of cell communication and signaling. 2018;12(1):69-82. PMID: 29260442.
  8. 13Jing X, et al. Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia. American journal of respiratory cell and molecular biology. 2024;70(2):94-109. PMID: 37874230.
  9. 14van Willigenburg H, et al. Cellular senescence as a therapeutic target to improve renal transplantation outcome. Pharmacological research. 2018;130:322-330. PMID: 29471104.
  10. 15Krimpenfort P, et al. Rejuvenation by Therapeutic Elimination of Senescent Cells. Cell. 2017;169(1):3-5. PMID: 28340347.
  11. 16Liu BH, et al. [Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2017;42(16):3065-3071. PMID: 29171222.
  12. 17Deryabin PI, et al. Targeting Multiple Homeostasis-Maintaining Systems by Ionophore Nigericin Is a Novel Approach for Senolysis. International journal of molecular sciences. 2022;23(22). PMID: 36430735.
The FOXO4-DRI Report · $19

Everything you need to start.

Dose, sourcing, safety, our verdict. One purchase. Yours forever.

Built from 17 cited studies.

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