FOXO4-DRI common uses, half-life, side effects and more
Also known as Proxofim
About
FOXO4-DRI is an experimental peptide made to kill senescent cells. Senescent cells have stopped dividing but do not die. They build up with age and release signals that inflame the tissue around them. People buy FOXO4-DRI for anti-aging and longevity self-experiments. It has never been given to a person in a study of any kind. It is not approved as a medicine anywhere and is sold only as a research chemical. The scientist whose lab created it has publicly warned people not to inject it.
Common uses
- Clearing senescent cells that build up with age
- Anti-aging and longevity self-experiments
- General vitality and energy in later life
- Long-standing joint and back pain in a few individual reports
Frequency
Three to six doses every other day, repeated at most a few times a year
Dosing
Subcutaneous doses among people who have actually injected it run from 1 mg to 33 mg every other day for three to six doses. No consensus exists inside that range. The high cluster of 25 to 33 mg comes from scaling the animal dose to human body size. Only about four people are on record running it. The popular 1 to 3 mg cluster is far cheaper and traces to a single figure from one podcaster. Every published animal study used 5 mg/kg for three doses on alternate days. Scaling that dose to an adult by body surface area gives roughly 24 to 30 mg per injection. The standard vial holds 10 mg. One scaled dose therefore costs about two and a half vials. The 1 mg dose costs a tenth of one vial. Cost rather than any safety or effect finding is what separates the two clusters. Microgram ladders and 5 days on 2 days off schedules circulate widely online and trace only to auto-generated dosing sites.
Administration
- Doses run on alternate days and then stop for months rather than running continuously
- A single three-dose course still showed an effect in mice 30 days later so courses are spaced by months rather than by how fast the peptide clears
- A 10 mg vial covers one dose at the scaled amount or ten doses at the popular low amount
- Users wash out rapamycin, quercetin, and corticosteroids for one to two weeks first because those blunt cell death
- Intravenous protocols circulate online but no clinic was found offering it and no first-hand account describes it
Half-life
No plasma half-life has been measured for FOXO4-DRI in any species. No pharmacokinetic study of any kind has been published. Half-life figures of four to eight hours circulate on vendor pages and trace to no measurement.
Side effects
- Injection-site pain and swelling lasting about a day
- Fatigue building through a course rather than a discrete reaction after each dose
- Pins and needles the day after injecting in one account
- Flu-like symptoms claimed as the typical reaction on vendor pages with no first-hand account behind them
How it works
FOXO4-DRI targets the grip between two proteins called FOXO4 and p53. Senescent cells stay alive because raised FOXO4 traps active p53 in the nucleus and blocks the cell's self-destruct program. The peptide competes for p53 and pushes it out. The cell then dies by a route needing both p53 and the caspase enzymes. The killing step itself was carried over from earlier work rather than shown for this peptide. Structural work in 2025 found it binds a different part of p53 than the field had assumed. Several other proteins use that stretch and two carry out DNA repair. The cell-penetrating tail also helps grip p53 rather than only carrying the peptide in. It uses D-amino acids in reverse order to resist the enzymes that digest ordinary peptides.
Research quality
Eighteen papers mention FOXO4-DRI and none is a human study. No pharmacokinetic, dose-ranging, or toxicology study exists in any species. The founding 2017 paper reported senescent cells dying about twelve times more readily than normal ones and aged mice regaining fur, kidney function, and activity. Its own wording is conditional and says the peptide worked under conditions where it was tolerated without publishing what those were. Independent groups have since reported selective clearance in cartilage, testis, lung, and skin models. One 2022 comparison found the opposite and saw senescent cells resist it as strongly as normal ones. A 2023 study using this exact peptide made pulmonary hypertension worse in mice. Roughly ten to fifteen people have documented injecting it and the most-cited owned the company selling it.
Warnings
- Clearing senescent cells with this peptide raised lung artery pressure in mice and a rising lung artery pressure gives no warning symptom
- The same sequence built from ordinary amino acids failed to kill senescent cells in the founding study so a wrong-form product would do nothing
- The reversed mirror-image form has the same weight as the ordinary version so a certificate that only confirms molecular weight cannot tell the two apart
- Repeated senolytic dosing delayed wound healing and blocked liver and lung regeneration in animals so recent surgery or injury is a reason to wait
- Pregnancy, breastfeeding, and use in children have never been studied and cell senescence is required for normal development
- No dose has ever been raised until harm appeared in any species so the margin between a working dose and a dangerous one is unknown
Sources (19)
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Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging
Cell 2017 (PMID 28340339)
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The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI
Nature Communications 2025 (PMID 40593617)
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Targeting multiple homeostasis-maintaining systems by ionophore nigericin is a novel approach for senolysis, reporting senescent cells no more prone to death from FOXO4-DRI than normal cells
International Journal of Molecular Sciences 2022 (PMID 36430735)
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Eliminating senescent cells can promote pulmonary hypertension development and progression
Circulation 2023 (PMID 36515093)
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Senescent cells, senolytics and tissue repair, the devil may be in the dosing
Nature Aging 2023 (PMID 37118118)
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Limitations of peptide retro-inverso isomerization in molecular mimicry
Journal of Biological Chemistry 2010 (PMID 20382735)
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Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells
EBioMedicine 2021 (PMID 34689087)
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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)
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FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Aging 2020 (PMID 31959736)
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Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes
Frontiers in Bioengineering and Biotechnology 2021 (PMID 33996787)
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FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells, including the safety testing on non-senescent cells
Experimental Gerontology 2024 (PMID 39025385)
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How to plan and carry out a simple self-experiment, a single person trial of senolytic peptide FOXO4-DRI
Fight Aging 2018
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Peptide chiral purity determination by hydrolysis in deuterated acid and derivatization with Marfey's reagent, the method needed because mirror-image amino acids share one mass
Journal of Pharmaceutical and Biomedical Analysis 1995 (PMID 7633594)
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Interview in which the originating researcher calls self-injection of the peptide bizarre, dangerous, and life-threatening
NVON, reporting Erasmus MC
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FOXO4-DRI writeup relaying the Ben Greenfield dose, with the author stating he has never used the compound
Jay Campbell
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FOXO4-DRI 10 mg lyophilized vial listing, the standard unit sold
Core Peptides
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Prohibited list section S0, covering any pharmacological substance with no approval for human therapeutic use
World Anti-Doping Agency 2026
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Bulk drug substances nominated for use in compounding under section 503A, which does not list FOXO4-DRI in any category
US Food and Drug Administration 2026
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Think twice about injecting peptides bought online
Health Canada 2026