FOXO4-DRI: The Definitive Guide

The senolytic peptide, the 2017 mouse study, the selectivity problem and what people report.

FOXO4-DRI at a glance.

FOXO4-DRI at a glance. A synthetic peptide of 46 amino acids, built entirely from mirror-image (D) building blocks in reversed order, with the printed sequence Leu-Thr-Leu-Arg-Lys-Glu-Pro-Ala-Ser-Glu-Ile-Ala-Gln-Ser-Ile-Leu-Glu-Ala-Tyr-Ser-Gln-Asn-Gly-Trp-Ala-Asn-Arg-Arg-Ser-Gly-Gly-Lys-Arg-Pro-Pro-Pro-Arg-Arg-Arg-Gln-Arg-Arg-Lys-Lys-Arg-Gly. It has two joined parts: a segment copied from the region of FOXO4 that grips p53, and a segment derived from an HIV TAT sequence that carries it into cells. Formula C228H388N86O64, molecular mass 5,358.2 daltons. Also called Proxofim. In purified-protein work it binds the flexible front end of p53 with a dissociation constant of 400 plus or minus 280 nanomolar; in cultured senescent cells, active p53 left the nucleus and the cells self-destructed; and fast-aging and naturally aged mice showed better fur and kidney markers, with running-wheel activity improving in the fast-aging strain only. In several later experiments using human cells, healthy cells died as readily as senescent ones. No human dose has been established: FOXO4-DRI has never been given to a person in a published study, no register searched holds a trial of it, and no blood level has been measured in any species. Status: investigational, with no approval found in any register searched; no FDA substance record; not on the US compounding lists checked; covered by the anti-doping ban on substances without approval for human use, although not named on the list.

FOXO4-DRI

A mirror-image copy of the part of the FOXO4 protein that grips p53, built to make worn-out cells destroy themselves

Also called Proxofim · FOXO4 D-retro-inverso peptide · FOX04 (a common misspelling)

Synthetic peptide (46 amino acids), all-D retro-inverso, in two joined parts: a FOXO4-derived p53-interacting segment and a TAT-derived cell-penetrating segment

46 amino acids C₂₂₈H₃₈₈N₈₆O₆₄ 5,358.2 Da Synthetic

Synthetic; first reported 2017 from Erasmus University Medical Center, Netherlands

L, D-Leu, position 1, other
T, D-Thr, position 2, other
L, D-Leu, position 3, other
R, D-Arg, position 4, basic
K, D-Lys, position 5, basic
E, D-Glu, position 6, acidic
P, D-Pro, position 7, proline
A, D-Ala, position 8, other
S, D-Ser, position 9, other
E, D-Glu, position 10, acidic
I, D-Ile, position 11, other
A, D-Ala, position 12, other
Q, D-Gln, position 13, other
S, D-Ser, position 14, other
I, D-Ile, position 15, other
L, D-Leu, position 16, other
E, D-Glu, position 17, acidic
A, D-Ala, position 18, other
Y, D-Tyr, position 19, other
S, D-Ser, position 20, other
Q, D-Gln, position 21, other
N, D-Asn, position 22, other
G, Gly, position 23, other
W, D-Trp, position 24, other
A, D-Ala, position 25, other
N, D-Asn, position 26, other
R, D-Arg, position 27, basic
R, D-Arg, position 28, basic
S, D-Ser, position 29, other
G, Gly, position 30, other
G, Gly, position 31, other
K, D-Lys, position 32, basic
R, D-Arg, position 33, basic
P, D-Pro, position 34, proline
P, D-Pro, position 35, proline
P, D-Pro, position 36, proline
R, D-Arg, position 37, basic
R, D-Arg, position 38, basic
R, D-Arg, position 39, basic
Q, D-Gln, position 40, other
R, D-Arg, position 41, basic
R, D-Arg, position 42, basic
K, D-Lys, position 43, basic
K, D-Lys, position 44, basic
R, D-Arg, position 45, basic
G, Gly, position 46, other

Basic(positively charged): Arg, Lys
Acidic(negatively charged): Glu
ProlinePro
Other
D outlineEvery bead is a mirror-image (D) amino acid, except the four glycines

Bead positions show amino-acid order, not the 3D structure. Where the two parts meet is not published, so the beads between the brackets carry neither label.

How researchers think it works

In cell and animal studies; never tested in people

Competes for p53
It binds the flexible front end of p53, the part FOXO4 grips in senescent cells.
Purified-protein study
Moves p53 out
In treated senescent cells, active p53 left the nucleus and the cells self-destructed.
Cell study
Changed aging mice
Fast-aging and naturally aged mice showed better fur and kidney markers. Running-wheel activity improved in the fast-aging strain only.
Animal study
Selectivity failed
In several human-cell experiments, healthy cells died as readily as senescent ones.
Cell studies

Discussed for

Clearing worn-out (senescent) cells, skin, joints, energy

Dose

No established human doseNever given to a person in a study; no blood level measured in any species

Safety exception: no protocol shown

Human evidence

NoneNo trial in any register checked; human cells and tissue studied only outside the body

All evidence is from dishes and animals

Status

Investigational; no approval found in the registers checked
No FDA substance record and no ingredient identifier
Not on the US compounding lists checked
Covered by WADA S0 (unapproved substances); not named

Conceptual summary: bead positions show amino-acid order, not a 3D structure. Mechanism panels summarize cell and animal findings. No human study of FOXO4-DRI has been published, and no human dose has been established.

Published by DoserlyUpdated September 27, 2026Next scheduled review: December 202643 min readHow this guide was made

In this guide

Key takeaways

What it is: a lab-made chain of 46 amino acids, built as a mirror image of a natural sequence, designed to make worn-out cells destroy themselves. It is also sold as Proxofim and, on some sites, as FOX04. Animal studies injected it intravenously (into a vein), intraperitoneally (into the abdominal cavity) and, in one toxicity study, subcutaneously (into the fatty layer under the skin). No half-life has been measured in any species. [1], [2]
No established dose: FOXO4-DRI has never been given to a person in a published study, and no register we checked holds a trial of it. The amounts on websites run from 250 micrograms to about 33 milligrams an injection, and higher still where a page multiplies an amount per kilogram by body weight. They are copies of each other and of arithmetic done on a mouse dose. [3], [4], [26], [45]
Evidence: one influential 2017 mouse and cell study, and about 27 further cell and animal experiments since. Later work in human cells repeatedly failed to reproduce its selectivity for worn-out cells. [1], [6], [7]
Safety: the only repeated-dose animal toxicity study, run by the developer's own company, found lower body weight and raised liver enzymes, liver weight and platelets in mice given the highest amount they tolerated, eight times. Mice given half that amount showed much smaller changes, close to those of the comparison peptide. In one lung-disease mouse model, clearing worn-out cells made the disease worse. [2], [8]
Legal status: no approval and no medicines-register entry was found in the United States, Canada, Australia, the United Kingdom or the Netherlands. It is covered by the anti-doping ban on substances with no approval for human use. [9], [10], [11], [12], [13]

Study and website amounts · The selectivity problem · Common questions

What is FOXO4-DRI?

FOXO4-DRI is a manufactured peptide, a chain of 46 amino acids, designed to make senescent cells destroy themselves. Senescent cells are cells that have stopped dividing but have not died, and which build up in tissue as animals age. A substance meant to kill senescent cells is called a senolytic. FOXO4-DRI has been tested in cells and in animals since 2017, and it has never been given to a person in a published study. [1], [3]

The name describes the design. FOXO4 is a protein that, in senescent cells, holds another protein called p53 in place and keeps the cell alive. DRI stands for D-retro-inverso: the chain is written backwards and built from D-amino acids, the mirror-image form of the usual building blocks. That construction was chosen so the chain would be harder for the body's protein-cutting enzymes to break down, although how long FOXO4-DRI actually survives in a body has never been measured. [1]

The chain has two working parts joined together: a stretch copied from the region of FOXO4 that grips p53, and a short positively charged tail, based on a sequence from HIV, that carries the whole thing through cell membranes. Researchers at Erasmus University Medical Center in the Netherlands built it and patented it, and a spin-out company has since moved on to two different successor peptides. You will also see FOXO4-DRI called Proxofim, and the misspelling "FOX04", with a zero in place of the letter O, is common enough that dosing pages and product listings use it in their own titles and web addresses. The key term is investigational: after nine years, it remains a laboratory tool. [1], [14], [15], [16], [17], [18]

Conceptual illustration of a patch of connective tissue in which most cells look ordinary while a few are enlarged, flattened and irregular, releasing small signalling particles into the space around them. It shows a biological concept, not an effect of FOXO4-DRI. — Senescent cells stop dividing but stay alive, change shape, and release signalling molecules into the tissue around them. This illustration explains a concept from cell and animal research; it is not microscopy or clinical evidence.

Typical FOXO4-DRI Protocols

CautionNo human dose has been established, and there is no way to work one out. FOXO4-DRI has never been given to a person in a published study, no register we checked holds a trial of it, and no study in any species has measured how long it stays in the blood. The only repeated-dose animal toxicity study found raised liver enzymes, raised platelets and lower body weight in mice given the highest amount they tolerated. [3], [2]

Animal amounts are in milligrams per kilogram of body weight and are never converted to human doses. Culture concentrations in micromolar describe liquid around cells in a dish, not a dose. Most website amounts are flat amounts for a person; a few are given per kilogram of body weight. [1], [3]
Who or what	Amount	How often	How long	What was found or claimed
Used in studies
Mice given the chemotherapy drug doxorubicin (2017)	5 mg per kg, into a vein	Days 1, 3 and 5	3 injections	Less weight loss, and lower blood AST and urea, than untreated mice [1] A mouse experiment, not a plan for people
Fast-aging XpdTTD mice (2017)	Not stated in the text; the schedule is only in a figure image	Not verified	30 days of treatment, 7 to 8 mice per group	Better fur density, running-wheel activity and kidney markers [1] The number of injections inside those 30 days is not published in readable text
Naturally aged mice, older than 110 weeks (2017), main arm	Not stated in the text; the schedule is only in a figure image	Not verified	30 days of treatment	Better fur density and responsiveness, better kidney markers, platelets unchanged [1] Running-wheel activity varied too much in these mice to be tested
Naturally aged mice, older than 110 weeks (2017), kidney-marker arm	5 mg per kg, into the abdominal cavity	Every other day	3 injections, measured 30 days later	Lower blood urea and creatinine, matching a genetic method of clearing the same cells [1] A separate figure panel from the row above; kidney markers only
Aged male mice, 20 to 24 months (2020)	5 mg per kg, into the abdominal cavity	Every other day	3 injections, measured 30 days later	Blood testosterone rose; body and testis weight did not change [19]
Naturally aged and chemically aged mice (2026)	5 mg per kg, into the abdominal cavity	Every 2 days	1 month, or 4 weeks	Better measures of blood-vessel aging; liver and kidney blood tests unchanged [20]
Newborn rat pups exposed to high oxygen (2024)	10 mg per kg, into the abdominal cavity	Days 4, 6, 8 and 10 of life	4 injections	Cells staining for one senescence marker fell from 18.2% to 8.6%; lung structure improved slightly [21]
Mice, toxicity study (2025 preprint), higher arm	The highest single amount the mice tolerated; the actual figure is not published	Twice weekly, subcutaneously (into the fatty layer under the skin)	8 injections over 4 weeks	Lower body weight, higher liver-to-body weight, higher platelets, ALP, AST and ALT [2] The only repeated-dose toxicity dataset that exists
Mice, toxicity study (2025 preprint), lower arm	Half that amount	Twice weekly, subcutaneously	8 injections over 4 weeks	Body weight and platelets in line with the comparison groups; ALP, AST and ALT far below the higher arm, close to the comparison peptide's values; the liver-to-body weight ratio fell only part of the way [2] The same study; the large blood changes above were seen only in the higher arm
Human and animal cells in a dish	6 to 50 micromolar in the liquid around the cells	Once, or renewed over the experiment	2 hours to 5 days	Senescent cells died in some experiments; healthy cells died in others [1], [6], [22], [7] A concentration in a dish is not a dose for a body
Website claims
A 16-week daily escalation	250 mcg, rising to 375 mcg, then 500 mcg	Once daily	16 weeks, about 45.5 mg in total	The same three phases and week boundaries on 7 pages, with much of the wording identical; no study behind it [4], [23], [24], [25], [26], [27], [28]
Low-milligram alternate-day claims	1 to 5 mg an injection	Every other day	3 or more injections	Three pages carry this family; the spacing resembles the mouse figure, the amount does not [29], [30], [33]
A wide flat range, Peptide Protocol Wiki	3 to 25 mg an injection	Every other day	3 to 6 injections a cycle, 1 to 3 cycles a year	Given as the range of community protocols, with no source [32]
Twice or three times a week, Peptides Institute	1 to 5 mg an injection	Two to three times a week	During a cycle; no length given	Called an investigational human range, with no study behind it [18]
Three injections over three weeks, Everything Peptide	1 to 3 mg an injection	Three injections over 3 weeks	Short cycles	A wider spacing than any study used [31]
One milligram, five days on and two off	1 mg, or 1 to 5 mg on one page	Once daily on 5 days a week	2 weeks, repeated several times a year	Ten injection days empty one 10 mg vial exactly, as one page points out [34], [35], [33]
Days 1, 3 and 5 copied from the mouse study	1 to 5 mg an injection	Days 1, 3 and 5	3 injections, repeated monthly on one page	The days come from the 2017 mouse figure; the human amounts are additions [36], [37]
Consecutive-day pulses	1 to 10 mg an injection	Once daily	2 to 5 days in a row	No page names a source, and no mouse schedule in the paper used consecutive days [38], [17], [39]
Body-surface-area arithmetic	About 0.4 mg per kg, the output of the sum	Every other day	3 injections, or 5 in a forum PDF	The mouse 5 mg per kg divided by a standard conversion factor of 12.3. Arithmetic, not a measured dose [29], [34], [36], [41] Pages in this family turn that figure into a flat amount for an adult, about 25 to 36 mg, and four more print that result without the working [23], [33], [5], [26]; this guide records the sum and not its output
High flat amounts, PepGuide	25 to 33 mg an injection	Days 1, 3 and 5	3 injections over 6 days, 75 to 100 mg a cycle	Presented as based on the mouse 5 mg per kg; the same page also carries the 16-week ladder [26]
High flat amounts, Peptigraph	5 to 10 mg an injection	Three times a week	3 to 4 weeks	Attributed by the page to grey-market and forum sources, with no study behind the numbers [42]
High flat amounts, Real Peptides	5 to 10 mg an injection	Every 3 to 5 days	A 10 to 14 day course	The page attributes the spacing to early self-experimentation and the amount to animal studies; no study used these amounts in a person [43]
High flat amounts, Biomogging	10 to 25 mg an injection	Every other day	3 to 7 injections, once or twice a year	Attributed to biohacker practice, with no source [5]
Per-kilogram claims, My Peptide Story	0.05 to 0.5 mg per kg	3 to 5 injections	1 to 2 weeks	A per-kilogram range with no source for the numbers [44]
Per-kilogram claims, FormBlends	1 to 2 mg per kg	Once to three times a week	A 3-week course, given as an example	Described by the page as scaling the mouse amount down; 80 mg an injection for an 80 kg adult [45]
Per-kilogram claims, The Peptide Catalog	2 to 5 mg per kg	3 days on, 4 days off	3 to 6 weekly cycles	The mouse amount per kilogram used with no species conversion, which the page says lands at 150 to 375 mg an injection [34]

Read the units: mcg means micrograms; 1 mg equals 1,000 mcg. Animal amounts are per kilogram of body weight. Cell-study amounts are concentrations in the liquid around cells, written in micromolar, and they describe an experiment in a dish. Most website amounts are single flat numbers for any adult, and a few are per kilogram of body weight. These are four different things, and no measurement exists that would let anyone convert between them for this peptide. [1], [2]

Because no dose has been established, this guide does not convert any of these amounts into syringe units and does not describe how to mix or inject the powder.

The website numbers are shown so you can recognise them, not because any has been found safe or effective. The next chapter explains where each one came from. They come from copied pages, mouse arithmetic and forum practice rather than from any study in people. [4], [29], [3]

Where these numbers come from

Study rows. The mouse rows come from the original 2017 paper, whose figure legends give the route, amount and spacing for the chemotherapy arm: three injections into a vein at 5 mg per kg on days 1, 3 and 5. The naturally aged mice are split into two rows because the paper's Figure 7 describes two different things. Its main panels cover mice treated for 30 days on the same timeline as the fast-aging arm, a timeline published only inside a figure image, so this guide states no injection count for it. A separate panel reports blood urea and creatinine in mice given three injections into the abdominal cavity at 5 mg per kg, every other day, measured 30 days later. The fast-aging arm is published as a 30-day treatment in three pooled groups of 7 to 8 mice, with the same unstated injection count. The aged-mouse testosterone row, the blood-vessel row and the newborn-rat row come from their own papers, each checked against the original text. The toxicity rows come from a 2025 preprint by the developer's company; it plots two arms for each peptide, the acute maximum tolerated amount and half of it, and states the number of injections and the route but not the milligrams per kilogram. [1], [19], [20], [21], [2]

Website rows. We compared 27 dosing, calculator and product pages and checked each quoted number against the page. They fall into 11 numeric families, and one of them is largely the same text on different sites. The 250, 375 and 500 microgram ladder appears with identical phase lengths on PeptideDosage.org, PeptideDosages.com, DosagePeptide, Peptide Dosing Protocols, PepGuide, PeptiJournal and a French-language page, and with the same 3 mL mixing instruction on all of them except the French-language page, which uses 2 mL; the earliest dated fully readable copy we found is from November 2025, and none of the pages credits the ladder to an originator or to a study. The 1 to 5 milligram alternate-day family covers three pages, on PeptideWiki, Peptide Protocol Wiki and Peptide Initiative, while a second Peptide Protocol Wiki page, Peptides Institute and Everything Peptide give their own amounts or spacing and are listed separately. The high flat amounts sit on four pages that do not agree with each other: PepGuide, Peptigraph, Real Peptides and Biomogging, each with its own frequency and course length, which is why they are listed separately above rather than combined. The body-surface-area calculation is worked through on PeptideWiki, The Peptide Catalog, PeptideDeck and a PDF posted to a public forum; PeptideDosage.org, Peptide Initiative, Biomogging and PepGuide print its result without the working, and Peprimo prints a matching flat amount of about 25 milligrams with no working at all. [4], [23], [24], [25], [26], [27], [28], [29], [30], [31], [18], [32], [33], [5], [43], [42], [41], [40], [34], [36]

What we left out. We did not turn any animal amount into a human dose, average the website numbers, combine one page's amount with another page's course length, or treat a concentration in a dish as a dose. Four pages perform arithmetic that divides the mouse 5 mg per kg by a body-surface-area factor of 12.3, which some write as multiplying by 3 over 37, to reach about 0.4 mg per kg; that calculation is recorded as arithmetic and is never shown here as an amount for a person. One published paper prints a culture concentration a thousand times higher than every comparable study, which we treat as a printing error and do not reproduce. Open the searchable source directory [29], [34], [36], [41], [19]

What is FOXO4-DRI commonly used for?

Almost everyone who looks into FOXO4-DRI is looking into the same idea: that clearing out worn-out cells might slow or partly undo the effects of aging. The specific hopes attached to it are skin quality, joint and back pain, energy, and a general sense of being biologically younger, and the original paper's chemotherapy result draws its own interest. [46], [47], [29], [1]

The appeal comes from one study. In 2017, a Dutch team reported that FOXO4-DRI restored fur density and kidney blood markers in both fast-aging and naturally aged mice, restored running-wheel activity in the fast-aging strain, and reduced the damage that chemotherapy did to healthy mouse tissue. Those results were striking, widely reported, and have never been repeated in a person. [1]

Everything below is animal or cell research unless it says otherwise. It describes what was measured in mice, rats and dishes. It is not a list of effects in people.

Aging, skin and general "rejuvenation"

The 2017 mouse work is the whole basis of the anti-aging interest. In naturally aged mice older than 110 weeks, and in a strain of fast-aging mice, the authors reported better fur density and improved kidney blood markers after treatment, together with better responsiveness to gentle handling. Running-wheel activity improved in the fast-aging strain, where the untreated animals ran about 1.4 kilometres a day against about 9.4 for normal mice. In the naturally aged mice the authors state that wheel activity varied too much between animals to test at all, which is worth knowing because websites often cite the two groups as one result. [1]

A 2026 study in mice of about 17 months reported improvements in the aging of the aorta and the cells lining blood vessels, using 5 mg per kg into the abdominal cavity every two days for a month. A cell study on keloid scar tissue found that FOXO4-DRI pushed senescent scar fibroblasts into apoptosis, the body's orderly form of cell self-destruction. Neither involved treating a person. [20], [48]

Conceptual illustration of the inside of a cell: a nucleus with a protein held against it by a partner protein, and a separate ribbon-like peptide arriving so that the held protein moves out into the surrounding cell fluid. It represents cell and animal research, not a demonstrated effect in people. — The idea behind FOXO4-DRI: it is built to compete for the grip that FOXO4 keeps on p53 inside a senescent cell, so that p53 moves out of the nucleus and the cell self-destructs. This generated illustration explains a concept from cell and animal research; it is not microscopy or clinical evidence.

Chemotherapy side effects

The original paper's most concrete result was not about aging. Mice given the chemotherapy drug doxorubicin lost less weight, and had lower blood AST and urea, when they also received three injections of FOXO4-DRI into a vein. A Russian group later reported that FOXO4-DRI given with a chemotherapy drug produced moderate protection of liver cells and less fatty and white-cell infiltration in mice, with a difference between the sexes, although the underlying paper's numbers were not available to us. [1], [49], [50]

The same group reported the opposite kind of finding in the gut: a pronounced cell-killing effect in the fast-renewing lining of the small and large intestine. Because doxorubicin was given alongside, the two effects cannot be separated. [51]

Lung disease and radiation injury

Lung research is the largest cluster after the original paper, and it points in two directions. In mice given bleomycin, a drug used to create lung scarring in the laboratory, two separate groups reported less scarring and less collagen after FOXO4-DRI, one of them using 5 mg per kg on days 14, 16 and 18. One of those papers had to correct duplicated figure panels in 2024; the authors state the conclusion is unchanged. A further Chinese-language report described reversal of radiation-induced lung scarring in mice. [52], [53], [54], [55]

Against that, a 2023 study in mouse models of pulmonary hypertension found that removing senescent cells made things worse: pressures in the lung circulation, blood-vessel remodelling and measures of the right side of the heart all deteriorated. These are different diseases in different models, and they cannot be added together into a general lung effect. [8]

Cancer research

FOXO4-DRI appears in cancer laboratories as a tool for killing cells that chemotherapy or radiation has pushed into senescence, not as a cancer treatment. In cultured non-small-cell lung cancer cells it increased the effect of radiation; in mice with lung tumours, injections on days 1, 3 and 5 each week for two cycles made radiation more effective while reducing radiation scarring in the lung. In cultured glioblastoma cells it increased the effect of temozolomide. Other groups use it as the benchmark their own new peptides must beat. [56], [57], [58], [59], [60]

No study has tested whether FOXO4-DRI treats or prevents any cancer in a person, and the idea that a senolytic prevents cancer has no support. Senescence is one of the body's own brakes on tumour growth, which is a reason for caution rather than confidence. [61]

Fertility and testosterone

Two mouse studies are the source of a claim you will meet often. In aged male mice, three injections of 5 mg per kg every other day raised blood testosterone when measured 30 days later, without changing body or testis weight. A 2024 study reported better sperm production in aged mice. Human testis samples appeared in the first study only as tissue that researchers looked at; nobody was treated. [19], [62]

Joints, discs and pain

In a mouse nerve-injury model, 10 micrograms injected directly into the fluid around the spinal cord once a day for five days reversed late-stage pain sensitivity in male mice for between 2 and 11 days. It did nothing in females, and nothing in young mice of either sex. That is a narrow, sex-specific result from a route nobody uses outside a laboratory. [63]

Expanded human cartilage cells in a dish lost their most worn-out population after five days at 25 micromolar, but their ability to form cartilage afterwards did not improve, which was the point of the experiment. A 2025 report combined FOXO4-DRI with other ingredients in slow-release microspheres for spinal disc degeneration in rats, so the peptide's own contribution cannot be separated out. [22], [64]

See what is known in people or explore the animal and cell research.

Where do FOXO4-DRI amounts differ, and why?

Because no study has established a human dose, every human-facing number online was built from something else: a mouse dose, a conversion factor, a vial size or a forum post. Knowing which one tells you how much weight to give it.

Why do the amounts differ by more than a hundredfold?

Because nothing anchors them. The website figures run from 250 micrograms an injection to about 33 milligrams as flat amounts, and into the hundreds of milligrams where a page multiplies an amount per kilogram by body weight. The 11 numeric families we found were built from copied page text, the timing of one mouse study, arithmetic on that study's amount per kilogram, the size of the vial on sale, and forum practice nobody verified. None rests on a measurement in people, so there is nothing to check them against. A range that wide is not a dose range; it is the absence of one. [4], [5], [65]

A diagram tracing where the dosing numbers on 27 FOXO4-DRI web pages come from. Six starting points on the left connect to eleven families of numbers on the right. Copied page text feeds the sixteen-week daily ladder, which carries the same phases and much of the same wording on seven sites (DosagePeptide, the earliest dated copy from November 2025, PeptideDosage.org, PeptideDosages.com, Peptide Dosing Protocols, PepGuide, Guide des Peptides and PeptiJournal), none of which credits an originator. The timing of the 2017 mouse study feeds the alternate-day family (four pages) and the mouse days 1, 3 and 5 family (three pages). Arithmetic on the mouse amount per kilogram feeds body-surface-area arithmetic (five pages), the mouse days family and per-kilogram scaling of the mouse amount (one page). The size of the vial on sale feeds the alternate-day family, five days on and two off (three pages) and the mouse days family. Forum or biohacker practice that nobody verified feeds weekly-spaced courses (three pages), every three to five days and the once- or twice-yearly pulse (one page each). No traceable source lies behind the consecutive-day pulse (three pages), a wide per-kilogram range (one page) or two of the weekly-spaced pages. Five pages appear in more than one family, and PeptideDeck and Peptide Initiative each carry different families on different pages. No amounts are plotted, and no average or recommended amount is shown. None of the 27 pages rests on a measurement in people. — Twenty-seven dosing pages, eleven families of numbers, traced back to what each was built from. Only the sixteen-week ladder shares its wording across sites; the other links rest on matching timings, arithmetic that reproduces the numbers, or the page's own attribution. No amounts are plotted, and none of the pages rests on a study in people. Sources: Protocol sources in the directory · Baar et al., Cell (2017).

Where does the 250, 375 and 500 microgram ladder come from?

From other websites. Seven pages carry the same three phases, the same week boundaries and, on six of them, the same mixing instruction for a 10 mg vial. The earliest dated readable copy we found is from November 2025, and none of the pages credits the ladder to an originator or to a study. Added up, the ladder delivers about 45.5 milligrams over 112 days of daily injections, a schedule no experiment in any species has tested. [4], [23], [24], [26], [28]

Is 0.4 mg per kg a scientifically derived human dose?

No. It is the mouse figure of 5 mg per kg divided by 12.3, a standard factor used to compare doses between species by body surface area. That arithmetic is a first step regulators use when planning a first study in people, not a result. It assumes the drug behaves comparably in both species, and for FOXO4-DRI nobody has measured how it behaves in either. Four pages show the working and several more print its result as a flat amount of about 25 to 36 milligrams. This guide records the calculation and does not present its output as an amount for a person. [29], [34], [36], [41], [1]

Why does the mouse timing keep appearing?

Because "every other day, three times" is the one thing in the 2017 paper that is easy to copy. Several pages keep that spacing and then attach a flat milligram amount to it that has nothing to do with the study. The original figure legends describe 5 mg per kg given into a vein on days 1, 3 and 5 for the chemotherapy arm, and the same amount into the abdominal cavity every other day for one naturally aged kidney-marker panel. Neither route is what websites recommend. [1], [36], [37]

Does the vial size decide the dose?

In practice, often yes. FOXO4-DRI is sold mainly in 10 mg vials, with 2, 5 and 15 mg sizes also listed, and several website schedules divide neatly into exactly one 10 mg vial: ten days at 1 mg, or three injections of about 3.3 mg. In public discussions people say so directly, describing amounts chosen because that is what they had, such as a whole 10 mg vial in one dose or one vial a day for ten days. One page states outright that its middle option is set by price rather than by evidence. [34], [36], [65], [91]

Where do the pages get the science wrong?

Check a page's facts before trusting its numbers. Pages describe FOXO4-DRI as having 49, 47, 43 or even 18 amino acids; the published sequence has 46. Some give a molecular weight of about 4.8 kilodaltons, or about 2.3; the published figure is 5,358.2 daltons. One page says the original mouse study injected daily and several say three times a week, when the schedules the paper states are every other day. [1], [67], [34], [44], [29], [45], [25], [32], [43], [23]

Is there a safe maximum?

No number has ever been established as safe in a person, so there is nothing to describe. In the one repeated-dose animal study, mice received the highest single amount they tolerated, twice a week for eight injections, and developed raised liver enzymes, raised platelets and lower body weight. A second group given half that amount showed much smaller changes, close to those of the comparison peptide. The paper does not publish what either amount was in milligrams per kilogram, so neither number can be located, let alone divided down. [2]

What happens when you stop FOXO4-DRI?

Nobody knows what happens in people, because nobody has been studied. The animal studies give a partial answer: in one 2017 panel measuring kidney markers in naturally aged mice, and in a 2020 aged-mouse study, three injections were followed by a 30-day gap before anything was measured, and the differences the authors reported were still present at that point. Nothing was measured later than that, in any study. [1], [19]

There is no evidence of a withdrawal effect, a rebound or a need to taper, and none has been looked for. No reasoning from the mechanism can fill that gap either. Whether senescent cells come back after a course, and how fast, has not been followed in any species, so the question of what stopping does is simply open. [1]

In public discussions, the unwanted effects people describe are short-lived and settle after the last injection, usually within days, although one person still had tingling and hot flushes ten days later. One person who reported abnormal kidney, liver and electrolyte blood tests after a course said repeat tests improved after stopping, with other explanations also in play. Another reported that improvements they had attributed to the peptide partly reversed over the following months. These are single accounts, not a pattern. [68], [69], [86]

Does it matter how FOXO4-DRI is given?

It almost certainly does, and nobody has measured it. The 2017 paper used two different routes in two different experiments, intravenous (into a vein) for the chemotherapy arm and intraperitoneal (into the abdominal cavity) in the aging experiments that compared it with a genetic method of clearing senescent cells. Intraperitoneal injection is a laboratory route for rodents; it is not used for this kind of product in people. Almost every other animal study since has used the abdominal route. [1], [19], [57], [20]

The only study to use subcutaneous injection, into the fatty layer under the skin, was the 2025 mouse toxicity study, which is also the study that found the liver and platelet changes. Websites and public discussions almost all describe subcutaneous injection, and one page offers intramuscular injection, into a muscle, as an option. A PDF circulated on a public forum argues for the intramuscular route on the grounds that it might resemble the mouse abdominal route more closely, which is an assumption rather than a measurement. [2], [17], [41]

One mouse study injected 10 micrograms directly into the fluid around the spinal cord. That route exists in the research record and nowhere else. [63]

How long does FOXO4-DRI last in the body?

Nobody knows. No study in any species has published FOXO4-DRI's half-life, how much of an injection reaches the blood (bioavailability), where it goes or how it is cleared. That entire field, pharmacokinetics, is blank for this peptide. [1], [2]

Two figures are often quoted as if they filled that gap, and neither does. The 2017 paper reports that the peptide could be detected inside cultured cells 2 to 4 hours after it was added and remained detectable for at least 72 hours; that is an antibody stain in a dish, not a blood level. The 2025 preprint reports that a peptide cleared from mouse plasma within two hours and stayed detectable in liver for up to 72 hours; that measurement is for CL04183, the successor compound, not for FOXO4-DRI. [1], [2]

The mirror-image construction is expected to slow enzymatic breakdown, and the original authors pointed to an unrelated mirror-image peptide that had been given to healthy volunteers as evidence that the class can be administered. That is an argument about a category, not a measurement of this molecule. [1]

How should FOXO4-DRI be stored, and how long does it keep?

No stability study of FOXO4-DRI has been published. We searched for one specifically, pairing the peptide's names with stability, storage, degradation and freeze-thaw testing, and found nothing. How long it stays usable, before or after mixing, is not established. [1]

What is on the record is how a laboratory handled it. The original researchers stored the freeze-dried powder at −20 °C (−4 °F) in one-milligram portions specifically to avoid repeated freezing and thawing, dissolved it in phosphate-buffered saline fresh for each experiment, and kept the animal solution on ice until injection, warming it to room temperature immediately beforehand. Those are handling conditions for research material used the same day, not a shelf life. [1]

Everything else you will read comes from dosing and product pages, and they do not agree. Ten pages we checked all say to keep the powder cold, most naming −20 °C (−4 °F) and some allowing 2 to 8 °C (36 to 46 °F), nearly all name bacteriostatic water as the mixing liquid, and all name 2 to 8 °C for the mixed solution. Where they part company is how long the mixed solution lasts: their stated limits run from about two weeks to about a month, and two pages give no limit at all. None of them cites a stability study for FOXO4-DRI, so the spread is not a disagreement between measurements. It is a disagreement between guesses. One page contradicts itself, saying both never to freeze the mixed solution and to freeze portions of it for long-term storage. One says outright that no long-term solution stability data exist, which is the accurate statement. [29], [23], [24], [4], [28], [34], [35], [36], [38], [5]

Cold storage cannot tell you what is in a vial. A "research use only" label does not verify a product's identity, purity, sterility or suitability for injection, and for this peptide the identity question is unusually live. See product quality.

What do we actually know about FOXO4-DRI in people?

Nothing directly. No person has been given FOXO4-DRI in any published study, and no register we searched holds a trial of it.

Conceptual comparison of cells in a laboratory dish, an animal study notebook, and human study records. Each answers a different research question. A lab finding cannot by itself establish patient benefit. — Cell studies explore biological activity. Animal studies explore effects in another species. Human studies must test outcomes in people. For FOXO4-DRI, the evidence stops before the human stage entirely.

Has anyone registered a trial?

No. A direct search of the ClinicalTrials.gov programming interface returned zero studies for FOXO4-DRI, for FOXO4 DRI, for Proxofim and for "senolytic peptide". The one record that mentions FOXO4 is an unrelated lymphoma trial that does not involve the peptide. Searches of the UK register, the European Union's clinical-trials system and Japan's national register each returned zero as well. [3], [70], [71], [72]

A wider sweep of the World Health Organization's international portal and of the Australian, Japanese university, Korean, Iranian and pan-African registers also found nothing, and the Chinese, Indian and Brazilian registers could not be searched by name. The honest summary is that no register we could search holds a FOXO4-DRI study, which is not the same as proving that nobody anywhere has been given it.

Then why do human cells and tissues keep appearing in the research?

Because human material can be studied outside a body. Human skin, lung, cartilage, bone-marrow, womb-lining, scar-tissue, muscle and cancer cells have all been exposed to FOXO4-DRI in a dish, and human testis and lung tissue has been examined alongside animal experiments. None of that is a person receiving a treatment. A concentration in a dish is not a dose, and a cell that dies in a well does not tell you what a milligram does in a body. [1], [22], [6], [48], [7], [73], [19], [21]

What happened to the development programme?

The inventor founded a company to develop senolytic peptides, and that company has moved on from FOXO4-DRI. Its public material names two successor compounds, CL04177 and CL04183, reports completed formal toxicology work in rats and non-human primates during 2025, and describes manufacturing work aimed at a future application to run a clinical trial. In August 2026 the company said CL04183 had reached readiness to file that application and that it was preparing to start a first study in people in 2027, in cancers where p53 is faulty. It did not say the application had been filed or accepted, and it did not name a country or a single condition. FOXO4-DRI itself is not the compound being taken forward. [16], [74], [75], [76]

The 2025 preprint makes the reason fairly plain. It compares FOXO4-DRI against CL04183 in mice, each at its own highest tolerated amount and at half of it, and reports that FOXO4-DRI produced liver and platelet changes at the higher amount while the successor did not at either. Because each peptide was measured against its own tolerance ceiling rather than a shared amount, that is not a comparison of equal doses, and it comes from the company with an interest in the successor. It is still the only repeated-dose safety comparison that exists. [2]

What would a meaningful human result look like?

It would start much earlier than most readers expect. Before anyone could ask whether FOXO4-DRI helps, a study would have to show what dose a person can tolerate, what blood levels that produces, and whether senescent cells actually fall. None of those three measurements exists, in any species for the first two. A change in how someone feels, without them, cannot be attributed to the peptide. [3], [2]

How might FOXO4-DRI work?

The research on how FOXO4-DRI works comes from purified proteins, cultured cells and mice. It explains the design. It does not show that the same thing happens in a person.

The idea

In the senescent cells the original team studied, p53 was active but held at the nucleus by FOXO4, which stopped it from triggering the cell's self-destruction. FOXO4-DRI was built as a decoy: a copy of the part of FOXO4 that grips p53, which competes for that grip. In those experiments, treated senescent cells moved active p53 out of the nucleus and died through apoptosis, while dividing control cells alongside them were less affected. Whether that sequence runs the same way in every senescent cell, or in a person, has not been shown. [1]

What the binding measurements actually show

A 2025 structural study measured the interaction directly and refined the picture. In the tube, FOXO4-DRI attaches to the flexible front end of p53, its transactivation domain. The strength of that attachment, its dissociation constant, was 400 ± 280 nanomolar against the first 94 amino acids of p53. Against one unmodified piece of that region on its own it was far weaker, at 18.5 ± 3.6 micromolar. It did not attach at all to the part of p53 that grips DNA. Adding phosphate groups to p53, the kind of chemical tag that appears when a cell is stressed, strengthened the binding. The study also found that the cell-penetrating tail contributes to the grip rather than only carrying the peptide inside. [77]

Three points follow. Binding is not the same as reaching a target inside a living body. The study was part-funded by the developer's company, and two authors held shares in it. And figures you may see quoted in the nanomolar range from a different paper belong to shorter fragment peptides, not to FOXO4-DRI. [77]

How quickly does anything happen?

In cultured cells, the peptide was detectable inside cells 2 to 4 hours after it was added and remained detectable for at least 72 hours, and loss of cell viability appeared as early as 24 to 36 hours. Those are the only timing numbers the original paper gives. They describe a dish. Claims that effects appear in a person after 10 to 14 days match nothing in the paper. [1]

Why the selectivity matters more than the mechanism

The whole safety case for a senolytic rests on the claim that it kills senescent cells and spares the rest. In the original experiments that held. In several later experiments using human cells, it did not. A 2021 study of human bone-marrow stem cells found the concentration that killed half the cells over five days was lower in non-senescent cells (44.4 ± 1.8 micromolar) than in three senescent groups (53.1, 57.7 and 56.4 micromolar), which is the opposite of the intended behaviour. A 2023 study of muscle stem cells reported that FOXO4-DRI eliminated cells in both the patient and the healthy-control groups, while a different senolytic in the same experiment was selective. A study of womb-lining stem cells found no useful selective loss at all. [6], [7], [73]

Where selectivity was found, the margin was modest. In keloid scar cells, the concentration needed to kill half the senescent cells was 34 micromolar against 94 micromolar for the non-senescent ones, a window of under three-fold. In cancer-associated lung fibroblasts, one group calculated a selectivity index of about six. Those are laboratory margins in specific cell types, not a safety margin in a body. [48], [57]

Does removing senescent cells always help?

No, and this is the most important thing the mechanism does not tell you. Senescent cells are not only debris. They help wounds close: in mouse skin wounds, suppressing the rapid senescence response that follows an injury delayed closure, while suppressing it later in repair did not, and an earlier study traced the effect to a growth factor those cells release. They help the liver regenerate after part of it is removed. And senescence is one of the barriers that stops damaged cells becoming tumours, which is why it appears in human pre-cancerous lesions and fades as those lesions progress. [78], [79], [80], [61]

The FOXO4-DRI record shows the same ambiguity. After one type of kidney injury, senescent cells fell but scarring and tubule damage did not improve. In a different kidney model, damage and scarring improved while the senescent-cell measure did not change. In pulmonary hypertension, removal made the disease worse. Clearing senescent cells is a change, not automatically a benefit. [81], [82], [8]

What are the risks and unanswered questions?

Is FOXO4-DRI safe?

Nobody knows, and the specific reasons to worry are unusually concrete. FOXO4-DRI is designed to kill cells. Its selectivity for senescent cells failed in several human-cell experiments. The one repeated-dose animal toxicity study found liver-enzyme, platelet and body-weight changes at the highest amount the mice tolerated. No dose has been shown to be tolerable in a person, because no person has been studied. [6], [2], [3]

Conceptual illustration of two laboratory dishes side by side holding the same concentration of liquid, one with ordinary cells and one with enlarged senescent cells, with a similar proportion of cells dying in each. It represents findings from cell studies, not an effect measured in people. — A senolytic is only useful if it kills worn-out cells at concentrations that leave healthy ones alone. In several experiments using human cells, the same concentration affected both. This illustration explains a finding from cell research; it is not microscopy or clinical evidence.

What did the animal safety work find?

Two datasets carry most of the weight, and they disagree.

The 2017 paper ran limited screens alongside its main experiments. It compared platelet levels before treatment and 30 days after and found no noticeable change, reported no change in other whole-blood values, found no apparent abnormalities in heart tissue sections, and reported no significant change in total body weight or kidney weight. Those were checks attached to its 30-day treatment experiments, not a toxicology programme, and the paper does not publish how many injections were given inside that window. [1]

A comparison of the two animal safety datasets for FOXO4-DRI. In 2017, limited screens attached to 30-day treatment experiments found no notable change in platelets, other whole-blood values, heart tissue, body weight or kidney weight. In a 2025 preprint, mice given eight injections at the highest amount they tolerated had lower body weight and higher liver-to-body weight, ALT, AST, ALP and platelet count; at half that amount the results were normal apart from liver-to-body weight, which fell only part of the way. Heart tissue and kidney weight were not reported. Caveats: the 2025 amount in milligrams per kilogram is unpublished, each peptide was dosed against its own tolerance ceiling rather than a shared amount, its methods and figure disagree on the schedule, and it is a preprint from the company developing the comparator. — The two animal safety datasets for FOXO4-DRI point in opposite directions. The 2017 screens were attached to 30-day treatment experiments whose injection count the paper does not publish; the 2025 preprint ran eight injections at the highest amount the mice tolerated and at half of it. Animal studies; small groups; each peptide was dosed against its own tolerance ceiling, so the 2025 arms are not a comparison of equal doses. Sources: Baar et al., Cell (2017) · Brand et al., preprint (2025).

The 2025 preprint is the only study designed to look for toxicity. Adult male mice, eight per group, received eight subcutaneous injections, twice weekly. The study ran two amounts for each peptide: the highest single amount the animals tolerated, and half of it. At the higher amount, the FOXO4-DRI mice lost body weight and showed a higher liver-to-body-weight ratio, a higher platelet count, and higher ALP, AST and ALT, the three blood markers used to detect liver injury. At half that amount the changes were much smaller: body weight matched the comparator groups, platelets sat inside the normal range the paper plots, and ALP, AST and ALT fell to about the level of the successor peptide's groups, close to the reference line the paper draws for each. The liver-to-body-weight ratio fell only part of the way and stayed above both arms of the successor peptide, which showed none of these changes at either amount. [2]

That dose split is the most useful thing in the study, and it cuts both ways. It is evidence that the effect is dose-related rather than unavoidable, and it is also the clearest demonstration that this peptide has an amount at which it damages an organ. Nobody can act on either half, because the paper does not publish what those amounts were in milligrams per kilogram. Three further caveats travel with it. Each peptide was dosed against its own tolerance ceiling rather than a shared amount, so the head-to-head is not a comparison of equal doses. The methods and the figure legend disagree about whether the four weeks of dosing were continuous or included a week off. And it is a preprint, not yet peer reviewed, written by the company developing the successor. It is still the only repeated-dose animal toxicity dataset that exists for FOXO4-DRI, and it points the other way from the 2017 screens. [2]

A 2026 mouse study that measured ALT, AST, urea and creatinine after a month of treatment found no statistically significant differences between groups, so the picture is not uniform. A small experiment inside a 2025 patent application reported that some blood-count results did not reproduce and that kidney markers varied. [20], [83]

A 2020 congress abstract from the same research group as the aged-mouse testosterone work reports a six-marker blood panel after three injections of 5 mg per kg into the abdominal cavity in aged mice: creatine kinase and its heart-muscle form CK-MB, ALT, AST, creatinine and urea, none of them significantly different between groups. The same abstract reports a significant drop in seminal-vesicle weight relative to body weight, with no significant change in testis weight relative to body weight, and does not explain it. It is a meeting abstract rather than a full paper, so it is low-grade evidence, and it overlaps the 2020 aged-mouse testosterone study set out in the fertility chapter rather than testing the peptide again. A normal result on six markers in one small mouse experiment is not a safety finding. [19], [113]

Could clearing senescent cells cause harm by itself?

That is a real possibility, not a theoretical one. In a mouse model of pulmonary hypertension, removing senescent cells worsened lung blood pressures, blood-vessel remodelling and right-heart measures, and in mice the senescence response is part of normal wound closing and liver regeneration. The mechanism chapter sets out that evidence. None of those studies measured what happens to a person who injects FOXO4-DRI; together they show why the mechanism cannot be assumed to work in one direction only. [8], [78], [80]

What problems have users reported?

Personal accounts describe a consistent set of effects, none of it controlled and none of it with a verified product. The one described most often is a local reaction: burning or stinging beginning within minutes of injection and lasting from a few hours to a day or two, and for several days in a few accounts, with redness, welts, palpable lumps, and in one case a darkened or scabbed injection site. One person described a mild burning feeling across an area roughly ten inches wide for a few hours; another stopped a course because an itchy, red reaction at the site was getting stronger with each injection. [65], [69], [84], [85]

A flu-like spell with aching and heavy fatigue, usually within a day or two of an injection, is the second recurring pattern, along with headache, dizziness, feeling warm or flushed, nausea, and disturbed sleep. Two accounts stand out and should be read carefully rather than dismissed or over-read. One person reported severe, sustained high blood pressure beginning one to three days after two small injections, with dizziness, tingling in the limbs, sweats and hot flushes. They were already taking a blood-pressure medicine and took extra during the episode, and had paused several supplements before the course; their blood pressure had settled by day ten, while the tingling and hot flushes had not. Another reported abnormal kidney, liver and electrolyte blood tests after a course of roughly 3 to 6 milligrams three times a week, alongside casual growth-hormone use, with repeat tests improving after stopping. Neither can establish cause. [65], [86], [68], [66]

Could product quality change the risk?

Yes, and here it is close to the centre of the problem. FOXO4-DRI is sold as a "research use only" powder, and that label gives no assurance that a product has been checked for identity, purity or human use. This peptide has a specific identity problem on top of the usual ones: what makes it FOXO4-DRI rather than an ordinary peptide is that every amino acid is the mirror-image form, and a standard purity certificate does not show that. In the reviewed public discussions, nobody had an analysis establishing the mirror-image form of what they injected. One poster in the 2017 group-purchase thread, who had not joined the purchase and imported his own supply, described sending samples for mass-spectrometry testing and finding the mass consistent with the peptide. He noted himself that the test could not tell the mirror-image form from the ordinary one, and no test of the material the group distributed was ever posted. [65]

The naming makes that harder. Pages and listings use "FOXO4-DRI" and the misspelling "FOX04" interchangeably, including in their own titles and web addresses. In public discussion people describe receiving vials they could not make sense of, ask whether a product sold as "FOXO4" is the same thing, or puzzle over listings such as a 50 milligram tablet to swallow. [17], [18], [65], [47], [87]

Is FOXO4-DRI legal? Is it FDA-approved?

Checked September 23, 2026. Rules differ by country and change quickly.

United States. FOXO4-DRI is not a medicine approved by the US Food and Drug Administration (FDA). It has no entry at all in the FDA's global substance registration system, which means it has not even been assigned an ingredient identifier. It does not appear on the FDA's lists of bulk substances that pharmacies or outsourcing facilities may use in compounding, checked in their May 2026 and March 2025 versions, nor on the list of compounding ingredients that may present significant safety risks, checked in its April 2026 version. Not being listed does not make it permitted. [9], [10]

Canada. We found no Health Canada authorization for any FOXO4-DRI product. Health Canada published a general advisory in 2026 warning that unauthorized injectable peptides bought online can cause serious harm. [11]

Australia. We found no Australian approval. The Therapeutic Goods Administration warned in 2026 about the risks of importing unapproved peptide products. [88]

United Kingdom and European Union. The UK medicines products register returns no FOXO4-DRI entry, and neither does the Dutch medicines information bank, which matters because the Netherlands is where the peptide was developed. The European Medicines Agency's product search could not be queried by name during this research, so the accurate statement is that no authorization was found in the registers we were able to check, not that none exists anywhere. [12], [89]

A "research use only" label does not make a product legal to sell for human use, or safe.

Is FOXO4-DRI banned in sport? Does it show up on a drug test?

It is not named on the World Anti-Doping Agency's list, but the list's first category, S0, bans at all times any substance with no current approval by any government health authority for human therapeutic use, naming drugs in pre-clinical or clinical development as examples. FOXO4-DRI fits that description. The 2027 list, in force from 1 January 2027, adds "peptides" to those examples. Athletes should treat it as prohibited. [13], [90]

Whether a particular test would detect it is a separate question, and the reviewed sources give no detection window for FOXO4-DRI. That gap is not permission to use it.

Who should be especially cautious?

None of these groups has any safety data, because nobody does. Given that FOXO4-DRI is designed to kill cells, the absence matters more than usual.

Anyone with a current or past cancer. Senescence is one of the body's brakes on tumour growth, and removing senescent cells has never been tested for its effect on an undetected lesion. The idea that a senolytic prevents cancer has no support at all. [61]
People with liver disease or raised liver enzymes. The one repeated-dose animal study found raised ALP, AST, ALT and liver weight at the highest amount the mice tolerated. [2]
People with lung or pulmonary blood-vessel disease. Senescent-cell removal worsened one mouse model of pulmonary hypertension. [8]
People healing from surgery, a wound or a recent injury. The senescence response contributes to normal wound closing and to liver regeneration in mice. [78], [80]
People with autoimmune disease. This comes up repeatedly in public discussion with confident answers in both directions and no evidence behind either.
Pregnancy and breastfeeding. Nothing has been studied in pregnancy, in breastfeeding or in embryo development, in any species. A few mouse studies looked at male reproductive measures such as testosterone, which is a different question and establishes nothing about safety here. [19]
Under 18. No study includes young people, and this guide is written for adults.
Competitive athletes. It falls under the anti-doping ban on substances without approval for human use. [13]

Has FOXO4-DRI been tested alongside other medicines?

Once, and not in the way the question usually means. The 2017 mouse work gave FOXO4-DRI after the chemotherapy drug doxorubicin, which is a sequence rather than a test of whether two things interfere with each other. Beyond that, no interaction or combination-safety study has been published in any species, and none in people. [1] The combinations that appear in public discussion, with mitochondrial peptides, growth hormone, oral senolytics and antioxidant supplements, have never been studied together with FOXO4-DRI, and people also describe stopping GLP-1 medicines and growth-hormone-releasing compounds beforehand. The advice circulating in those discussions is to pause anti-inflammatory supplements and medicines, such as fish oil, curcumin or quercetin, around a course. It rests on a cell experiment in the 2017 paper, in which an anti-inflammatory steroid reduced the peptide's effect in a dish, and nobody has tested whether any supplement changes what it does in an animal or a person. Bring a complete list of everything you take to a pharmacist or doctor. [1], [65], [84], [86], [66]

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What should be monitored while using FOXO4-DRI?

There is no safe human dose and no monitoring plan, because there has been no human study. What exists is the list of things researchers chose to measure in animals. This describes those studies; it is not a personal testing plan, and any testing is a conversation to have with a clinician. [1], [2], [20]

Liver

This is where the clearest animal signal is. The 2025 mouse toxicity study ran blood chemistry on the day after the last injection and again two weeks later, and reported higher ALP, AST and ALT in the mice given the highest amount they tolerated, together with a higher liver-to-body-weight ratio. In the mice given half that amount the same three enzymes were far lower, close to the values of the comparison peptide. A 2026 mouse study measuring ALT and AST after a month of treatment found no significant group difference, so the two datasets do not agree. [2], [20]

Blood counts and platelets

Platelets are the one blood measure both animal datasets looked at, and they disagree. The 2017 study compared platelet levels before treatment and 30 days after and found no noticeable change, along with no change in other whole-blood values. The 2025 study found raised platelet counts after eight injections at the highest tolerated amount, and normal counts after eight injections at half of it. A small patent experiment reported blood-count effects that did not reproduce. [1], [2], [83]

Kidneys

Kidney measures were the original study's headline improvement in aged mice, and later work is mixed. The 2026 mouse study measured urea and creatinine and found no significant group difference. A separate mouse kidney-injury study found that reducing senescent cells did not improve tissue damage or scarring. One public account described abnormal kidney blood tests after a course, improving after stopping, with several other explanations present. [1], [20], [81], [68]

Body weight, heart and general observation

The 2017 study reported no significant change in total body weight or kidney weight and no apparent abnormalities in heart tissue. The 2025 study reported lower body weight in its higher arm. Nothing else in the animal record was systematically monitored. [1], [2]

What you cannot measure

There is no validated test of how many senescent cells a person carries, which is the measurement that would show whether anything worked at all. Researchers can measure candidate signals, such as the p16 gene switched on in sampled immune cells, marker panels on a tissue sample, or inflammatory molecules in blood, and a 2025 study describes those as possible markers for future trials. The 2024 international guidance on senescence research states that no single marker is enough to detect senescence in a living body, and no such test is clinically available. Symptom tracking, blood pressure, energy levels, skin condition, joint pain and sleep are what remain trackable, and none of them is specific to this mechanism. [92], [93]

What do people in public communities report?

Public discussion of FOXO4-DRI began on a longevity forum within weeks of the original 2017 paper and led to a group purchase within months, and the character of the conversation has not changed much since. The accounts below are selected discussions, not a survey, and no product in any of them was verified. [46], [65]

What do the positive reports look like?

They are subjective, and they are almost always confounded. People describe better skin or faded age spots, deeper sleep, better focus, easier urination, reduced joint or back pain, and a general sense of feeling "sprier". One person who took three large injections reported, ten days after the last one, that a patch on their arm had reduced by about 90 percent and a chest patch had gone. Another described knee pain still absent almost a year later. [65], [95], [69]

Many of those accounts have something else happening at the same time: other peptides before or after, a course of a different senolytic, stem-cell treatment, rapamycin, metformin, red-light therapy, or a serious illness with hospital stays shortly before. One person pricked age spots with a lancet, rubbed the peptide in with hand lotion, and two days later attributed the spots fading to the peptide, while noting that the pricking could explain it. [65], [95], [47]

Does everyone notice a difference?

No. Feeling nothing is a common outcome in these discussions. People report no discernible effect after courses of 2 milligrams every other day, after a single 10 milligram injection, after 40 milligrams in a day, after 50 milligrams over two injections, and after emptying a whole vial. One person in their late 80s, whose physician injected 10 to 20 milligrams at a time, had noticed nothing positive six weeks in and put that down to it being early. [94], [91], [96], [65], [47]

The framing that grows around this is worth noticing. The standard reply is that not feeling anything does not mean nothing happened, which is true and also unfalsifiable: with no test of senescent-cell burden, feeling worse, feeling nothing and feeling better later are all read as confirmation. [94], [84], [65], [47]

How much are people actually taking?

Across a much wider range than the websites describe, and the amount is often set by the vial rather than by a target. Reported amounts in public threads run from 20 micrograms to 40 milligrams an injection, with course totals from a fraction of a milligram to about 100 milligrams, and one person described 12 milligrams a day for ten days. Several posts contain units that cannot be interpreted at all, including one describing a "100ml needle at 60cc" and another that mixes grams and millilitres, and this guide does not guess at what those mean. People describe choosing an amount because it was what the vial or the kit held, such as a whole vial in one dose or a vial a day for ten days. [65], [95], [69], [66], [98], [91], [84], [97]

What about unwanted effects?

Injection-site burning is the complaint that comes up most, and one person described it as more intense and longer-lasting than with another peptide they use. Flu-like illness, fatigue, headache, feeling warm and nausea all appear. Some people report no local reaction at all, which, given that nobody has verified what they injected, is itself informative. People trade suggestions for reducing the burning; none has been tested, and this guide does not repeat injection technique. [65], [85], [84], [69], [91], [66]

Do people sequence it with other compounds?

Constantly, and on no evidence. A common pattern in peptide discussion is to run a senolytic first and then mitochondrial and repair compounds afterwards, on the reasoning that there is no point repairing cells you are about to remove, although some people describe doing it the other way round. One person reported that their other supplements seemed to work better afterwards. That observation has an obvious alternative explanation: the senolytic week is usually the one week when someone stops everything else. No study has compared any sequence. [91], [47], [65], [84], [85]

How can you judge a recovery story?

Ask what else changed at the same time, whether anything was measured rather than felt, whether the person came back weeks later, and whether the amount they describe is internally consistent. Unit confusion is widespread here: one post describes a subcutaneous injection made up "with 50ml of saline", another writes "3.33" with no unit at all, and a diary titled "25mg x3" records doses of 24, 27 and 26 milligrams, the first of them split across three injections. Ask also what was in the vial, because in these discussions nobody knows. [65], [84], [66]

These selected discussions are not a survey of all users, a response rate or a substitute for controlled studies. The risks section covers what the animal studies found.

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A learning path for FOXO4-DRI readers

Start with the basics What peptides are, how research compounds differ from approved medicines, and the safety questions to ask first.
Go deeper on senescence What senescent cells do, why removing them is not automatically good, and how senolytic evidence is graded.
Plan and track with your care team Turn what you learn into questions, lab work and a plan you can review with a professional.
Keep the tools close Checklists, tracking templates and quick-reference tables for peptides and bloodwork.

Plus community discussions where members share what they are tracking and what they are still unsure about.

How does FOXO4-DRI compare with other senolytics?

FOXO4-DRI is one of several compounds studied for clearing senescent cells, and it is the only one in this group that has never been given to a person in a study. The last row is not a senolytic at all; it is included because peptide discussions almost always place it immediately after one.

Compound	What it is	How it is given	How often	Human evidence	Approval status
FOXO4-DRI	A 46-amino-acid mirror-image peptide built to break the grip FOXO4 keeps on p53	Into a vein or the abdominal cavity in animal studies; subcutaneously (under the skin) in one animal toxicity study	Three injections in several experiments; others ran for a month, and the 2017 aging arms do not publish their injection count	None. No published study has given it to a person, and no register we searched holds a trial [3]	Not approved (legal status)
Dasatinib with quercetin	An approved cancer medicine paired with a plant flavonoid, the most-studied senolytic combination	Both taken by mouth	Dasatinib on 2 days and quercetin on 3 days, repeated every 28 days	A randomized trial in 60 postmenopausal women over 20 weeks missed its main bone-turnover measure (a median change of −4.1% against −7.7% in the control group, P=0.611). Earlier pilots in 14 and 9 people tested feasibility and tissue markers [99], [100], [101]	Dasatinib is FDA-approved for two specific leukaemias; the senolytic use is off-label and investigational [102]
Fisetin	A plant flavonoid sold as a dietary supplement and studied as an oral senolytic	Taken by mouth	2 consecutive days, then 28 days off, for 3 cycles	A randomized placebo-controlled knee-osteoarthritis trial in 74 people over 12 months found no significant difference in side effects between groups and no difference on its cartilage scan measure. Results so far are conference and journal abstracts [103], [104]	Sold as a supplement ingredient; not an approved medicine for any condition [105]
Navitoclax	A tablet that blocks the survival proteins cells use to avoid self-destruction, used as the benchmark senolytic in laboratory work	Taken by mouth	Daily in its largest trial	A phase 3 trial in 252 people with myelofibrosis gave everyone ruxolitinib and added navitoclax or a placebo. The navitoclax arm met the spleen-size measure (63.2% against 31.5%, P<0.0001), but that is a cancer outcome, not senescent-cell clearance, and it is the effect of a combination. Severe low platelet counts occurred in 54.0% against 19.2% [106], [107]	Not approved [108]
SS-31	A four-amino-acid peptide that targets mitochondria; not a senolytic, but commonly taken after one	Injected subcutaneously (under the skin)	Once daily	A phase 3 trial in 218 people with primary mitochondrial myopathy missed both of its main measures, with a walking-distance difference of −3.2 metres (P=0.69). A separate programme in Barth syndrome led to a narrow approval [109], [110]	Approved in the US in September 2025, under accelerated approval, only to improve muscle strength in Barth syndrome, and only in patients weighing at least 30 kg [110]

Two things stand out. Every comparator has been given to people in a registered trial, and several of those trials missed their main measure, which is what a real test of a senolytic idea looks like so far. And FOXO4-DRI is the only one of the five where the question "what happens in a person" has never been asked. No study has compared FOXO4-DRI with any of them in people. [3]

Common questions about FOXO4-DRI

Is FOXO4-DRI the same as Proxofim or FOX04?

Proxofim is a name the developer used for the same peptide, and it is used commercially as an alias. "FOX04", spelled with a zero in place of the letter O, is a misspelling of FOXO4 that has spread into page titles, web addresses and product listings. FOXO4 on its own is the natural human protein, not the peptide. If a listing does not say "DRI" or "D-retro-inverso", there is no way to tell from the name what is in the vial. See what it is. [15], [17], [87]

Has FOXO4-DRI failed a human trial?

No, and this claim circulates widely enough to be worth answering directly. There has never been a human trial to fail. A direct search of ClinicalTrials.gov returned zero records, as did the UK, European Union and Japanese registers. The development company has moved on to two successor peptides, which is a business decision about which molecule to take into people, not a failed trial. See what is known in people. [3], [16], [74]

Does the mouse dose of 5 mg per kg translate to a human dose?

No. Converting an animal dose into a human one requires knowing how the drug behaves in both species, and for FOXO4-DRI nobody has measured that in either. Four websites divide 5 mg per kg by a body-surface-area factor of 12.3 to reach about 0.4 mg per kg, and others print that result as a flat amount. That arithmetic is a planning step before a first human study, not a result, and this guide does not present its output as an amount for a person. See where the numbers come from. [1], [29], [34], [36]

How long does FOXO4-DRI take to work?

There is no answer, because there is no measured effect in a person to time. The numbers you may see quoted are from a dish: the peptide was detectable inside cultured cells 2 to 4 hours after it was added, and cell viability started falling 24 to 36 hours later. Neither is a timeline for a person, and nothing in the research puts a number on one. See how it might work. [1]

Is FOXO4-DRI safe for someone with a cancer history?

No study has looked, and the reasoning that it should be safe runs backwards. Senescence is one of the mechanisms that stops damaged cells becoming tumours, and it appears in human pre-cancerous lesions for that reason. Removing senescent cells has never been tested for its effect on an undetected lesion. Claims that FOXO4-DRI prevents cancer growth have no support in any source we reviewed. See who should be especially cautious. [61], [3]

Does it clear senescent cells and spare healthy ones?

That was the design, and it worked in the original experiments. It has failed in several later ones. In human bone-marrow stem cells, non-senescent cells were more sensitive than senescent ones over five days. In muscle stem cells, both patient and healthy-control cells were eliminated. Where selectivity did hold, the margin was under three-fold in one study. Selectivity appears to depend on the cell type and the experiment, not to be a fixed property of the peptide. See why selectivity matters. [6], [7], [48]

Is it legal to buy FOXO4-DRI?

It is sold openly as a "research use only" chemical, and that label is the point: it means the product is not offered, tested or authorized for use in people. No medicines regulator whose register we searched lists an authorized FOXO4-DRI product, in the United States, Canada, the United Kingdom, the Netherlands or Australia. Health Canada and Australia's regulator have both published warnings about unapproved injectable peptides bought online. See legal status by region. [9], [10], [11], [88]

How would you know whether it did anything?

You would need a measurement, and there is not one. No clinically validated test exists for how many senescent cells a person carries, and the 2024 international guidance on senescence research says plainly that no single marker is enough to detect senescence in a living body. That is why the animal studies are the entire evidence base, and why a personal account of feeling better, taken while several other things changed, cannot answer the question. See what should be monitored. [92], [3], [47]

Glossary

Plain explanations of the route, dosing and research terms used in this guide. Underlined terms in the text link here.

Adverse event: A harmful or unwanted medical event reported after someone used a treatment. A report alone does not prove the treatment caused it.
ALP (alkaline phosphatase): A blood test used, among other things, to detect problems with the liver and bile ducts. It rose in mice given repeated FOXO4-DRI injections at the highest amount they tolerated.
ALT (alanine aminotransferase): An enzyme released into the blood when liver cells are damaged. A rise is one of the standard signals of liver injury.
Amino acid: A small chemical building block. Chains of amino acids make up peptides and proteins.
Animal study: Research in animals such as mice or rats. It shows what a substance does in a living body, but results in people can differ.
Apoptosis: An orderly process by which a cell destroys itself. FOXO4-DRI was designed to trigger it in senescent cells.
AST (aspartate aminotransferase): An enzyme measured in blood that rises when liver or muscle cells are damaged. It is usually read alongside ALT.
Bioavailability: The share of a dose that reaches the bloodstream. It has never been measured for FOXO4-DRI by any route.
Cell study (in vitro): Research on cells grown in a dish. It gives early clues about biology, but it is far from proof of benefit in people.
Compounding: When a pharmacy prepares a customized medicine from individual ingredients. In the US, federal lists control which bulk ingredients pharmacies may use.
Controlled trial: A study that compares people who receive a treatment with a similar group who do not, often receiving a placebo instead. None has ever been run for FOXO4-DRI.
Course and cycle: A course is the period of repeated use. A cycle is a course plus a planned break before any further use. Neither has been established for FOXO4-DRI.
Creatinine: A waste product that healthy kidneys clear from the blood. A rising level can signal kidney strain.
D-amino acid: The mirror-image form of an amino acid. The body's usual protein-cutting enzymes handle chains made of them poorly. Every amino acid in FOXO4-DRI is this form.
Daily total: All the amounts given in one day, added together. For example, 1 mg twice daily is a 2 mg daily total.
Dose (amount each time): The amount given on one occasion. A protocol lists both the dose and how often it is given. No human dose of FOXO4-DRI has been established.
FDA: The US Food and Drug Administration, which decides whether medicines can be sold in the United States. It has not approved FOXO4-DRI and holds no substance record for it.
GLP-1 medicine: A prescription medicine, such as semaglutide or tirzepatide, that copies glucagon-like peptide-1, a gut hormone, to reduce appetite and lower blood sugar.
Half-life: The time it takes for the measured level of a substance in the blood to fall by half. It has never been measured for FOXO4-DRI in any species.
Intramuscular (IM): Injected into a muscle. One website offers this as an option for FOXO4-DRI; no study has used it.
Intraperitoneal (IP): Injected into the abdominal cavity, the space around the organs in the belly. It is a common laboratory route in rodents and is not used for products like this in people.
Intrathecal: Injected into the fluid around the spinal cord. One mouse pain study used this route for FOXO4-DRI.
Intravenous (IV): Given directly into a vein, so it enters the bloodstream immediately. The 2017 chemotherapy mouse experiment used this route.
Investigational: Still being studied and not approved by a regulator to treat any condition. FOXO4-DRI has not reached the stage of being studied in people.
Dissociation constant (Kd): A number describing how tightly two molecules stick together. A smaller number means tighter binding. It measures chemistry in a tube, not an effect in a body.
Loading phase: A higher starting amount used in some treatment plans before a lower ongoing amount. None has been established for FOXO4-DRI.
mcg and mg: Micrograms and milligrams. 1 mg equals 1,000 mcg. Website amounts for FOXO4-DRI are written in both, which is one reason they are easy to misread.
mg per kg: Milligrams of substance for each kilogram of body weight. Animal study doses are written this way, and they cannot simply be applied to people.
Micromolar (µM): A measure of how concentrated a substance is in a liquid. It describes the fluid around cells in a laboratory dish and is not a dose for a body.
p53: A protein that decides whether a damaged cell repairs itself, stops dividing or self-destructs. It is often called a tumour suppressor because it helps stop damaged cells becoming cancer.
Phosphate-buffered saline (PBS): A salt solution used in laboratories to dissolve and dilute substances. The original FOXO4-DRI experiments used it to prepare fresh solutions.
Peptide: A short chain of amino acids. FOXO4-DRI is a chain of 46.
Pharmacokinetics: How the body absorbs, moves, breaks down and removes a substance. No such data have been published for FOXO4-DRI in any species.
Phase 1 trial: The first stage of testing in people, usually small, designed to find a tolerable dose and spot side effects rather than prove a benefit. FOXO4-DRI has never had one.
Placebo: A dummy treatment with no active ingredient, used as a comparison in studies. The animal studies used salt-solution injections this way.
Preclinical research: Studies done before research in people: cell studies and animal studies. All FOXO4-DRI evidence is preclinical.
Pulmonary hypertension: High blood pressure in the arteries that carry blood from the heart to the lungs. It strains the right side of the heart.
Rapamycin: A prescription medicine that suppresses the immune system, used after transplants and studied for aging. Some people in longevity discussions take it alongside other compounds.
Research use only: A label on products sold for laboratory research. It does not mean a product is approved, tested for human use or legal to sell as a medicine.
Retro-inverso: A way of rebuilding a peptide with its sequence reversed and every building block in mirror-image form, so the side chains line up in a similar pattern while the chain resists ordinary protein-cutting enzymes.
SASP: The senescence-associated secretory phenotype: the mixture of inflammatory and signalling molecules that senescent cells release into surrounding tissue.
Senescent cell: A cell that has permanently stopped dividing but has not died. Senescent cells build up with age and release signalling molecules, and they also play useful roles in wound healing and in stopping tumours.
Senolytic: A substance intended to kill senescent cells. FOXO4-DRI, dasatinib with quercetin, fisetin and navitoclax are all described this way.
Subcutaneous (SC): Injected into the fatty layer just under the skin. This is the route used in the 2025 mouse toxicity study and in almost every website schedule.
Titration: Adjusting a dose in steps, usually starting lower and increasing. No stepped schedule for FOXO4-DRI has been tested in any species.
Transactivation domain: The flexible front section of p53 that switches other genes on. It is the part FOXO4-DRI was found to bind.
WADA: The World Anti-Doping Agency, which publishes the list of substances banned in sport.

Explore more of the research

Go deeper into the experiments behind the claims.

Across this guide, the citations include 28 original cell and animal experiments involving FOXO4-DRI or used as direct comparators, plus two patent applications with small animal experiments, one congress abstract that overlaps one of those experiments, and four papers on senescence biology that did not use the peptide. There are no human studies, because none exists. Several papers come from the network that invented the peptide or from the company developing its successors, and those ties are noted where they matter. Registry searches, regulatory pages, dosing websites and personal accounts are counted separately.

In the route details below, intraperitoneal means into the abdominal cavity and intrathecal means into the fluid around the spinal cord.

The original 2017 study and its patents · 3 records

What did the study that started everything find?

Model: Human and mouse cells in culture; C57BL/6J mice given the chemotherapy drug doxorubicin; fast-aging XpdTTD mice; naturally aged mice older than 110 weeks.

Finding: Senescent cells in culture lost viability while dividing controls were less affected. Mice given doxorubicin lost less weight and had lower blood AST and urea. Fast-aging mice showed better fur density, running-wheel activity and kidney markers; naturally aged mice showed better fur density, responsiveness and kidney markers, with wheel activity too variable to test. The peptide was made by a contract manufacturer at above 95 percent purity, and its printed molecular mass is 5,358.2 daltons.

Limit: Small model-specific groups. Limited safety screens rather than a toxicology programme. The dosing schedule for the fast-aging arm appears only inside a figure image. No human administration and no pharmacokinetics.

[1]

What do the patents add?

Model: Patent claims plus small mouse experiments, about three animals per group in the comparison noted.

Finding: The 2016 application establishes the invention history and the claimed peptide architecture. A 2025 application reports a mouse comparison in which some blood-count effects did not reproduce and kidney markers varied.

Limit: Patent applications are not peer reviewed, the groups are very small, and the breadth of a claim is not evidence for each disease named in it.

[14], [83]

Does it kill the right cells? · 7 papers

Human bone-marrow stem cells

Model: Human bone-marrow mesenchymal stem cells made senescent by sulfur mustard or hydrogen peroxide, five-day exposure.

Finding: The concentration killing half the cells was 44.4 ± 1.8 micromolar in non-senescent cells against 53.1, 57.7 and 56.4 micromolar in the senescent groups. Healthy cells were more sensitive, not less.

Limit: One cell type, one laboratory, culture only.

[6]

Muscle stem cells from patients with myotonic dystrophy

Model: Myoblast cultures from patients and matched healthy controls, 48 hours.

Finding: FOXO4-DRI eliminated cells in both the patient and the control groups. A different senolytic tested alongside was selective.

Limit: Culture panel; the exact concentrations were in an inaccessible supplement.

[7]

Womb-lining stem cells

Model: Human endometrial mesenchymal stem cells, 25 micromolar for three days, in a study whose main subject was a different compound.

Finding: No selective loss of senescent cells compared with controls.

Limit: Culture only; FOXO4-DRI appears as one of several comparison senolytics.

[73]

Expanded cartilage cells

Model: Human donor chondrocytes expanded in culture, 25 micromolar for five days.

Finding: The most expanded cell population was removed and senescence markers fell, while minimally expanded cells were less affected. Their later ability to form cartilage did not improve.

Limit: The paper states eight donors but lists six ages. Culture outcome only.

[22]

Keloid scar cells

Model: Human keloid and normal skin fibroblasts and keloid tissue explants, typically 25 micromolar, with a viability series to 100 micromolar.

Finding: Senescent keloid fibroblasts underwent apoptosis, with active p53 moved out of the nucleus. The concentration killing half the cells was 34.19 micromolar in senescent keloid cells against 93.77 in non-senescent ones.

Limit: A window under three-fold. Tissue in a dish is not a treated person.

[48]

Cancer-associated lung fibroblasts

Model: Human lung fibroblasts pushed into a senescence-like state, 50 micromolar for 72 hours.

Finding: A selectivity index of about six was calculated in that system.

Limit: An induced laboratory phenotype, not a tissue in a body.

[57]

Designed competitor peptides

Model: Doxorubicin-senescent human A375 melanoma cells.

Finding: Two groups designed new peptides and used FOXO4-DRI as the benchmark. One reports its candidate reached a selectivity index about 1.2-fold higher at one threshold and comparable at another.

Limit: Comparative cell-model selectivity, not clinical efficacy.

[59], [60]

Organ and disease models · 11 records

Kidney injury

Model: Male C57BL/6J mice with folic-acid kidney injury, followed to 28 days; and a separate genetic kidney-disease mouse model treated on alternate days during weeks 1, 3, 5 and 7.

Finding: In the first, senescent cells fell but scarring, infiltration and tubule damage did not improve. In the second, kidney damage, scarring, inflammation and cell death improved while tubular senescence did not change. The two decouple markers from outcome in opposite directions.

Limit: Different models; peptide dosing detail was in an inaccessible supplement for the first.

[81], [82]

Lung scarring

Model: Mice given bleomycin, treated at 5 mg per kg into the abdominal cavity on days 14, 16 and 18, with an endpoint at day 21; plus a second bleomycin study and a Chinese-language radiation-fibrosis study in C57BL/6 mice treated at weeks 16 and 20 after irradiation.

Finding: Less scarring, less collagen and fewer myofibroblasts. In the first study the endothelial cell fraction was not rescued in the way a standard antifibrotic drug rescued it. The radiation study reports falls in collagen deposition and in two fibrosis genes.

Limit: The first paper published a correction in 2024 replacing duplicated figure panels. The second and third were available only as an abstract and an indexed translated excerpt.

[52], [53], [54], [55]

Pulmonary hypertension

Model: Mouse models of pulmonary hypertension, with human lung tissue examined separately and not treated.

Finding: Removing senescent cells worsened lung blood pressures, blood-vessel remodelling and right-heart measures.

Limit: Abstract access only; the dose and schedule could not be verified. This is the clearest harm signal in a disease model.

[8]

Newborn lung injury

Model: Sprague-Dawley rat pups kept in 95 percent oxygen from day 1 to day 10, treated at 10 mg per kg into the abdominal cavity on days 4, 6, 8 and 10.

Finding: The proportion of cells staining for GL13, a senescence-associated marker, fell from 18.2 ± 2.7 percent to 8.6 ± 2.2 percent, and the radial alveolar count rose from 11.0 ± 0.9 to 12.9 ± 1.0, against 16.0 ± 0.7 in room-air controls. Both figures are reported in a figure legend.

Limit: A neonatal rat model; human lung samples were autopsy tissue, not treated.

[21]

Testosterone and sperm production

Model: 20 aged male mice of 20 to 24 months with 10 young controls, given 5 mg per kg into the abdominal cavity every other day for three administrations and assessed 30 days later; plus a 2024 aged-mouse study.

Finding: Blood testosterone rose without a change in body or testis weight, and apoptosis in a Leydig-cell line rose from about 10 to 27 percent. The 2024 study reports better sperm production and less inflammatory secretion from Leydig cells.

Limit: The first paper prints a culture concentration of 25 millimolar twice, a thousand times higher than every comparable study, which this guide treats as a printing error. Human testis tissue was observed, not treated. The 2024 study was available as an abstract.

[19], [62]

Blood vessels

Model: Naturally aged mice from 17 months and chemically aged mice, both given 5 mg per kg into the abdominal cavity every two days for a month or four weeks; plus human umbilical vein cells at 50 micromolar.

Finding: Improved measures of aortic and endothelial senescence and of vascular function. ALT, AST, urea and creatinine showed no significant group differences.

Limit: Limited safety endpoints. The peptide was a commercial catalogue item rather than laboratory-made material.

[20]

Nerve pain

Model: Male and female mice after spared-nerve injury, given 10 micrograms in 5 microlitres into the fluid around the spinal cord once daily for five days.

Finding: Late pain sensitivity reversed in male mice for 2 to 11 days after injection. No effect in females, none in young mice of either sex, and no change in a senescence marker.

Limit: A route used nowhere outside the laboratory, and a sex-specific effect. The human data in the same paper were genetic and observational.

[63]

Cancer and radiation

Model: Human lung cancer cell lines at 6 and 30 micromolar applied 10 minutes before irradiation; mouse tumour and thoracic-irradiation models treated at 5 mg per kg on days 1, 3 and 5 each week for two cycles; human glioblastoma cells at 10 and 20 micromolar.

Finding: Viability and colony formation fell and apoptosis rose in irradiated lung cancer cells. Radiation worked better in the mouse tumour model and caused less lung collagen. Temozolomide worked better in the glioblastoma cells.

Limit: Two of the three were available only as abstracts, without absolute group values. None tested a cancer treatment in a person.

[56], [57], [58]

Chemotherapy protection and the gut

Model: Mice given a chemotherapy drug alongside FOXO4-DRI, reported by one research group in two papers and a university press release.

Finding: Moderate protection of liver cells, with less white-cell and fatty infiltration and a difference between the sexes; and a pronounced cell-killing effect in the fast-renewing lining of the small and large intestine.

Limit: Full texts were unavailable and the accessible material does not confirm the exact peptide. The chemotherapy drug's own effects cannot be separated from the peptide's.

[49], [51], [50]

Other comparator and combination work

Model: Primary human fibroblasts from three donors with idiopathic pulmonary fibrosis at 25 micromolar for 48 hours; and slow-release microspheres combining several ingredients in rat disc-degeneration models.

Finding: FOXO4-DRI served as a comparator senolytic in the fibroblast work, where the reported mouse reversal belongs to a different compound. The microsphere study reports improvement in disc degeneration for the combined formulation.

Limit: Neither isolates what FOXO4-DRI alone does in an animal.

[111], [64]

Why senescent cells are not simply debris · 3 papers

Senescent cells and wound healing

Model: Mouse skin-wound models in which senescent cells were removed, and a later study in mouse and pig skin injury in which the rapid senescence response was suppressed early or late.

Finding: Wounds closed more slowly without senescent cells, and supplying a growth factor those cells release restored normal closing. In the later study, suppressing the response early delayed closure while suppressing it later did not.

Limit: Animal skin wounds; FOXO4-DRI was not used in either. The 2014 paper received an editorial expression of concern in 2026, which is one reason the more recent independent study is cited alongside it.

[79], [112], [78]

Senescent cells and liver regeneration

Model: Young mice after removal of two thirds of the liver.

Finding: Eliminating senescent cells impaired the restoration of liver mass and delayed liver-cell division.

Limit: A surgical mouse model; no FOXO4-DRI and no FOXO4-targeting peptide.

[80]

Senescence as a brake on cancer

Model: Human pre-cancerous and cancerous lesions examined for senescence and DNA-damage markers.

Limit: Observational human tissue work. It does not test senolysis, and it does not show that any senolytic causes cancer.

Finding: Senescence, driven by DNA-damage checkpoints, acts as a barrier to malignant progression in early lesions.

[61]

How this guide was researched

This guide is built from a thorough review of the sources cited throughout it: published scientific studies, trial-registry searches, patent applications, regulatory documents and published dosing descriptions. We also reviewed public online forums and community education groups where people describe their own experiences with FOXO4-DRI.

The guide cites 113 sources, including 28 original scientific experiments using FOXO4-DRI or comparing directly against it. Each type of source answers a different question. Studies show what researchers measured. Dosing websites show what amounts are being promoted, not what is safe. Personal accounts show what individual people experienced. Every numbered citation links to its entry below, labeled by source type.

How this guide was made

Research and drafting were AI-assisted. Cited sources were checked against their originals, and each source entry notes when only an abstract, a snippet or a publication record was available. Where a published paper contradicted a widely repeated claim, we followed the paper. The guide was reviewed and edited by Doserly before publication. It has not had an independent clinical review, and Doserly does not currently have medical reviewers. Doserly makes a medication and health-tracking app and runs Doserly Academy, both of which are promoted in this guide. Read our editorial policy for how guides are researched, updated and corrected.

This guide is for educational purposes. It summarizes what the reviewed sources report so the research is easier to understand; it is not medical advice. For a deeper dive, or to check any point for yourself, go straight to the cited sources.

Explore the sources

These are the documents cited in this guide. Studies, dosing pages and personal accounts answer different questions. A source being listed does not mean every statement on its page is endorsed.

Evidence typeFind in sources

Showing 113 sources

01
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging ↗
Baar MP, Brandt RMC, Putavet DA et al. · Cell · 23 Mar 2017 · PMID 28340339
Cell / animal research
Original full text reviewed: sequence, molecular mass, supplier and purity; the route, amount and spacing of each mouse arm; and the limited blood, weight and heart screens. The dosing frequency of the fast-aging arm appears only inside a figure image and is not stated in readable text.
Disclosure: the senior author invented the peptide, is named on the related patent family, and later founded the company developing its successors.
02
Liver impairment by senescence is caused by hepatocyte reversal to a CD44-high de-differentiation state (preprint) ↗
Brand T, Lehmann J, van Essen-van Dorresteijn S et al. · Research Square preprint · Posted 18 Mar 2025
Cell / animal research
Original preprint reviewed in full: adult male mice, eight per group, eight subcutaneous administrations twice weekly, with blood chemistry on day 1 and day 14 after the last dose. Figure 7 plots two arms for each peptide, its acute maximum tolerated amount and half of it, so each peptide was dosed against its own ceiling rather than a shared amount. The milligrams per kilogram are not stated, and the methods and figure legend disagree on the calendar schedule. The preprint's separate statement that the comparator was dosed at least tenfold below its maximum tolerated amount belongs to its pharmacokinetic and liver-fibrosis experiments, not to this repeated-dose comparison.
Disclosure: a preprint, not yet peer reviewed. Several authors are affiliated with the company developing the comparator peptide, and the senior author is its founder, managing director and a shareholder.
03
ClinicalTrials.gov searches for FOXO4-DRI and its aliases ↗
ClinicalTrials.gov API v2 · US National Library of Medicine · Searched 23 Sep 2026
Registry search
Searches run directly against the programming interface: zero studies for FOXO4-DRI, FOXO4 DRI, proxofim and “senolytic peptide”. The single FOXO4 result, NCT07494565, is an unrelated lymphoma trial.
04
FOXO4-DRI (10mg Vial) Dosage Protocol ↗
DosagePeptide · 2025-11-26 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
05
FOXO4-DRI Protocol — Senolytic Dosage & Annual Pulse ↗
Biomogging · 2026-04-19 last updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
06
Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard ↗
Rothmiller S, Jäger N, Meier N et al. · Archives of Toxicology · 2021 · PMC7870771
Cell / animal research
Original full text reviewed: the five-day LC50 table, showing 44.4 ± 1.8 micromolar in non-senescent human bone-marrow stem cells against 53.1, 57.7 and 56.4 micromolar in the senescent groups.
07
Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1 ↗
Conte TC, Duran-Bishop G, Orfi Z et al. · Nature Communications · 2023 · PMID 37468473
Cell / animal research
Indexed excerpt reviewed: FOXO4-DRI eliminated cells in both the patient and the healthy-control groups over 48 hours, while navitoclax was selective in the same panel.
08
Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression ↗
Born E, Lipskaia L, Breau M et al. · Circulation · 2023 · PMID 36515093
Cell / animal research
Original abstract reviewed; the full text could not be opened, so the amount, route and schedule remain unverified. Pulmonary blood pressures, vessel remodelling and right-heart measures worsened after senescent-cell removal.
09
FDA Global Substance Registration System searches for FOXO4 and proxofim ↗
FDA GSRS · National Center for Advancing Translational Sciences · Searched 23 Sep 2026
Regulatory source
Substance searches for FOXO4, FOXO4-DRI and proxofim each returned zero results. No ingredient identifier (UNII) exists for this peptide.
10
FDA bulk drug substances for compounding: the 503A and 503B category lists and the significant-safety-risk list ↗
US Food and Drug Administration · 503A list updated 14 May 2026; 503B list updated 21 Mar 2025; safety-risk page current 22 Apr 2026
Regulatory source
Same-day copies of all three lists checked: no FOXO4-DRI, FOXO4 or Proxofim entry. Absence from a list is not permission.
11
Think twice before injecting peptides bought online: unauthorized products can seriously harm you ↗
Health Canada · Recalls and safety alerts · 2026
Regulatory source
Advisory reviewed: a general warning about unauthorized injectable peptides sold online. FOXO4-DRI is not named.
12
MHRA products register search for FOXO4-DRI ↗
Medicines and Healthcare products Regulatory Agency · United Kingdom · Searched 23 Sep 2026
Regulatory source
Register searched by a research assistant rather than opened by the lead: no FOXO4-DRI entry returned. The agency's published warnings about unauthorised medicines are general and do not name this peptide.
13
2026 Prohibited List ↗
World Anti-Doping Agency · In force 1 Jan 2026
Regulatory source
List text searched: FOXO4, proxofim and senolytic do not appear. Category S0 covers substances with no current approval by any government health authority for human therapeutic use.
14
Anti-senescence compounds and uses thereof ↗
de Keizer PLJ, inventor; Erasmus University Medical Center, applicant · WO2016118014A2 · 2016
Patent application
Application text reviewed for invention history and the claimed peptide architecture. The breadth of a patent claim is not evidence for any disease named in it.
15
British Society for Research on Ageing 2018 conference booklet ↗
British Society for Research on Ageing · 2018
Context and reviews
Booklet reviewed for the speaker biography in which the developer uses the name Proxofim.
16
Cleara Biotech (company site) ↗
Cleara Biotech · Checked 23 Sep 2026
Context and reviews
Pipeline pages reviewed: the company names CL04177 and CL04183 as its compounds and reports animal pharmacokinetics for them, not for FOXO4-DRI.
Disclosure: the company was founded by the peptide's inventor and has a commercial interest in the successor compounds.
17
FOXO4-DRI (FOX04) | Peptide Reference ↗
Peptide Protocol Portal · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
18
FOXO4-DRI: Research Profile & Guide ↗
Peptides Institute · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
19
FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice ↗
Zhang C, Xie Y, Chen H et al. · Aging (Albany NY) · 2020 · PMID 31959736
Cell / animal research
Original full text reviewed: 5 mg per kg into the abdominal cavity, three administrations every other day, assessed 30 days later. The paper prints a culture concentration of 25 millimolar twice, which this guide treats as a printing error and does not reproduce.
20
FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway ↗
Hu Z, Li F, Hu C et al. · Frontiers in Bioengineering and Biotechnology · 2026 · PMID 41625068
Cell / animal research
Original full text reviewed: 5 mg per kg into the abdominal cavity every two days for one month in naturally aged mice and four weeks in the chemically aged model; 50 micromolar in cultured cells. ALT, AST, urea and creatinine showed no significant group difference. The peptide was a commercial catalogue item.
21
Cellular Senescence Contributes to the Progression of Hyperoxic Bronchopulmonary Dysplasia ↗
Jing X, Jia S, Teng M et al. · American Journal of Respiratory Cell and Molecular Biology · 2024 · PMID 37874230
Cell / animal research
Original abstract and indexed methods reviewed: Sprague-Dawley rat pups, 10 mg per kg into the abdominal cavity on postnatal days 4, 6, 8 and 10. Human lung samples were autopsy tissue, not treated.
22
Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes ↗
Huang W, Hickson LJ, Eirin A et al. · Frontiers in Bioengineering and Biotechnology · 2021 · PMID 33996787
Cell / animal research
Original full text reviewed: 25 micromolar for five days in expanded human donor chondrocytes; later chondrogenic potential did not improve. The paper states eight donors but lists six ages.
23
FOXO4-DRI Dosage Chart, Schedule & Reconstitution Protocol ↗
PeptideDosage.org · 2026-05-21 last reviewed
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
24
FOXO4-DRI (10 mg Vial) Dosage Protocol ↗
PeptideDosages.com · 2026-03-04 published; 2026-09-20 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
25
FOXO4-DRI Peptide Dosing Guide: Senolytic Peptide Protocol (June 2026) ↗
Peptide Dosing Protocols · 2026-08 last reviewed
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
26
FOXO4-DRI: Research Profile, Mechanism & Protocols ↗
PepGuide · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
27
FOXO4-DRI : cellules sénescentes, p53 et reconstitution ↗
Guide des Peptides · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
28
FOXO4-DRI Research Protocol Reference ↗
PeptiJournal · 2026-08-07 last updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
29
FOXO4-DRI Dosage Guide ↗
PeptideWiki · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
30
FOXO4-DRI Dosing Calculator ↗
Peptide Protocol Wiki · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
31
FOXO4-DRI Dosage Protocol ↗
Everything Peptide · 2025-03 last reviewed
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
32
FOXO4-DRI: Dosing Protocols ↗
Peptide Protocol Wiki · 2026-01-29 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
33
FOXO4-DRI Dosage, Safety & Stacks ↗
Peptide Initiative · 2026-06-10 last updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
34
FOXO4-DRI Dosage Chart: 1mg Senolytic Protocol ↗
The Peptide Catalog · 2026-04-25
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
35
FOXO4-DRI Complete Dosing & Administration Guide ↗
Peptide Initiative · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
36
FOXO4-DRI Dosage Chart & Schedule Guide ↗
PeptideDeck · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
37
FOXO4-DRI Dosing Calculator & Protocol ↗
PepperCalc · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
38
FOXO4-DRI Dosing Guide: Complete Research Protocol ↗
Peptide Dojo · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
39
FOXO4-DRI Peptide: Benefits, Dosage & Side Effects (Complete Guide 2026) ↗
PeptideDeck · 2026-03-25 published; 2026-09-12 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
40
FOXO4-DRI ↗
Peprimo · Checked 23 Sep 2026
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
41
FOXO4-DRI Available for Research Use Only ↗
Rapamycin.News public PDF upload; document publisher unidentified · 2026-03 shown in document
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
42
FOXO4-DRI ↗
Peptigraph · 2026-09-14 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
43
How to Run FOXO4-DRI Cycle — Protocol & Safety Guide ↗
Real Peptides · 2026-07-06 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
44
FOXO4-DRI ↗
My Peptide Story · 2026-05-10 reviewed
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
45
FOXO4-DRI Dosage ↗
FormBlends · 2026-05-30 updated
Dosing website
Page reviewed and its quoted numbers checked against it. A dosing page describes what is being promoted, not what is safe or effective.
46
Destroying senescent cells with this peptide ↗
Longecity forum · 2017
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
47
FOXO4-DRI ↗
r/immortalists · Reddit · 16 Dec 2025
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
48
FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation ↗
Kong YX, Li ZS, Liu YB et al. · Communications Biology · 2025 · PMID 39994346
Cell / animal research
Original full text reviewed: typically 25 micromolar, with a viability series to 100 micromolar; IC50 34.19 micromolar in senescent keloid cells against 93.77 in non-senescent ones.
49
Morphological changes in the liver of experimental animals with combined introduction of adribastin and FOXO4-DRI ↗
Yakovlev AA, Vasiliev YuG, Shumikhina GV, Berestov DS · Vestnik NovSU · 2023
Cell / animal research
Original abstract reviewed (Russian-language journal); the full text was unavailable and the accessible material does not confirm the exact peptide.
50
Novgorod State University report on correcting cellular aging with a cell-killing agent ↗
Novgorod State University press office · 10 Feb 2026
Context and reviews
Press page reviewed. A university press summary is secondary and cannot verify the peptide's identity or selectivity.
51
Modulation of senescence-related changes in the small and large intestine of experimental animals with induced aging ↗
Yakovlev AA, Vasiliev YuG, Shumikhina GV, Karban OV et al. · Indexed 2025
Cell / animal research
Indexed excerpt reviewed; the primary paper was inaccessible. The chemotherapy drug's own effects cannot be separated from the peptide's.
52
FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway ↗
Han X, Yuan T, Zhang J et al. · Journal of Cellular and Molecular Medicine · 2022 · PMID 35510614
Cell / animal research
Original full text reviewed: 5 mg per kg into the abdominal cavity on days 14, 16 and 18 after bleomycin, with an endpoint at day 21. See the 2024 correction.
53
Correction to “FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway” ↗
Han XD et al. · Journal of Cellular and Molecular Medicine · 2024 · PMID 39166551
Context and reviews
Original full text reviewed: duplicated flow-cytometry panels in Figure 6B were replaced; the authors state the conclusion is unchanged.
54
FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice ↗
Liu Y, Hou Q, Wang R et al. · Naunyn-Schmiedeberg's Archives of Pharmacology · 2023 · PMID 37074394
Cell / animal research
Original abstract reviewed; full methods and dosing were not accessible.
55
FOXO4-DRI, a synthetic peptide targeting FOXO4, reverses radiation-induced lung fibrosis ↗
Han X, Yuan T, Song D et al. · Indexed by J-GLOBAL · 2023
Cell / animal research
Indexed machine-translated excerpt reviewed; the original article could not be opened. Treatment at post-irradiation weeks 16 and 20, endpoint at week 24.
56
A study of the FOXO4-DRI peptide increasing the radiosensitivity of non-small-cell lung cancer cells ↗
Zhao Y, Zhang J, Han X, Fan S · Chinese Journal of Radiological Medicine and Protection · 25 Dec 2019
Cell / animal research
Original abstract reviewed (Chinese-language journal): 6 micromolar in H460 and 30 micromolar in A549 cells, applied 10 minutes before irradiation. Absolute group values are not in the accessible text.
57
Targeting senescence-like fibroblasts radiosensitizes non–small cell lung cancer and reduces radiation-induced pulmonary fibrosis ↗
Meng J, Li Y, Wan C et al. · JCI Insight · 2021 · PMID 34877934
Cell / animal research
Original full text reviewed: 5 mg per kg into the abdominal cavity on days 1, 3 and 5 each week for two cycles; 50 micromolar for 72 hours in culture, with a calculated selectivity index of about six.
58
Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence ↗
Ning N, Wang C, Gao T et al. · Molecular Carcinogenesis · 2026 · PMID 42391447
Cell / animal research
Original abstract reviewed: 10 and 20 micromolar in a human glioblastoma cell line. The 82 patient tumour samples were used for correlation, not treated.
59
Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells ↗
Le HH, Cinaroglu SS, Manalo EC et al. · EBioMedicine · 2021 · PMID 34689087
Cell / animal research
Indexed excerpt reviewed: FOXO4-DRI used at 8 micromolar as the comparator for newly designed peptides.
60
Peptide inhibitors targeting FOXO4-p53 interactions and inducing senescent cancer cell-specific apoptosis ↗
Kang D, Lim Y, Ahn D, Lee J, Park C-J · Journal of Medicinal Chemistry · 31 Jul 2025 · PMID 40739602
Cell / animal research
Original full text reviewed. Counted once: the 2024 preprint and this article are the same experiment. FOXO4-DRI appears as the comparator.
61
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints ↗
Bartkova J, Rezaei N, Liontos M et al. · Nature · 30 Nov 2006 · PMID 17136093
Cell / animal research
Original full text reviewed. The human premalignant-lesion findings are observational; the causal test was in a mouse tumour model. It does not test senolysis.
62
FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells ↗
Li Y, Zhang C, Cheng H et al. · Experimental Gerontology · 2024 · PMID 39025385
Cell / animal research
Original abstract reviewed; full dosing and safety methods were not accessible.
63
Long-term male-specific chronic pain via telomere- and p53-mediated spinal cord cellular senescence ↗
Muralidharan A, Sotocinal SG, Yousefpour N et al. · Journal of Clinical Investigation · 2022 · PMID 35426375
Cell / animal research
Original full text reviewed: 10 micrograms in 5 microlitres into the fluid around the spinal cord, once daily for five days; effect in male mice only, none in young mice, and no change in a senescence marker.
64
Aging-Regulating Microspheres for Enhancing Mitochondrial Biogenesis in Early Senescence and Clearing Late Senescent Cells ↗
Xiang H, Yan C, Lei Y et al. · Advanced Functional Materials · 2025
Cell / animal research
Original abstract reviewed; full methods were not accessible. A combined formulation, so the peptide's own contribution cannot be isolated.
65
FOXO4 D-retro-inverso peptide group buy ↗
Longecity forum · From 5 Jun 2017
Community account
29-page thread read in full. Source of most of the large reported amounts, several injection-site reports, and the only description of independent product testing, of a sample imported separately by a poster who had not joined the purchase.
66
I did FOXO4-DRI full dose, 25 mg times three ↗
r/Biohack_Blueprint · Reddit · 14 Jul 2026
Community account
Thread read: a dated diary of four dosing days totalling about 80 mg. The title says three doses of 25 mg while the body gives 24 mg, split across three injections, then 27 and 26 mg, after a 3 mg test dose.
67
FOXO4-DRI (PubChem CID 167312269) ↗
PubChem depositors · National Library of Medicine · Record checked 23 Sep 2026
Reference entry
Compound record and properties response checked directly: formula C228H388N86O64 and molecular mass about 5,358. The CAS-style identifier attached to the record is a depositor synonym and the registration itself was not checked. The number 1627580-64-6, attached to FOXO4-DRI by the previous version of this page, resolves to MOTS-c, a different peptide.
68
Regret not ordering (page 2) ↗
Thinksteroids community forum · 28 Dec 2024
Community account
Thread read: the account of abnormal kidney, liver and electrolyte blood tests after a course, with casual growth-hormone use alongside and repeat tests improving after stopping.
69
FOXO4-DRI ↗
r/PeptideGuide · Reddit · Checked 23 Sep 2026
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
70
ISRCTN registry search for FOXO4 ↗
ISRCTN · BMC · Searched 23 Sep 2026
Registry search
Query interface called directly; the response reported a total count of zero trials.
71
EU Clinical Trials Information System public search for FOXO4 ↗
EU CTIS · European Medicines Agency · Searched 23 Sep 2026
Registry search
Public search interface called directly; the response reported zero total records.
72
jRCT (Japan Registry of Clinical Trials) search for FOXO4 ↗
jRCT · Japanese Ministry of Health, Labour and Welfare · Searched 23 Sep 2026
Registry search
Search page returned 該当するデータはありません, meaning no applicable data.
73
Targeting Multiple Homeostasis-Maintaining Systems by Ionophore Nigericin Is a Novel Approach for Senolysis ↗
Deryabin PI, Shatrova AN, Borodkina AV · International Journal of Molecular Sciences · 2022 · PMID 36430735
Cell / animal research
Original full text reviewed: FOXO4-DRI was one of the senolytics tested, at 25 micromolar for three days in human endometrial stem cells, with no selective loss of senescent cells.
74
Business progress ↗
Cleara Biotech · Checked 23 Sep 2026
Context and reviews
Company page reviewed: claims completed formal toxicology in rats and non-human primates during 2025 and drug-product work toward a clinical-trial submission. It does not establish that any submission was filed or accepted.
75
Cleara Biotech secures US and Chinese patent protection for CL04183 ↗
Cleara Biotech press release via BiotechNEWS.nl · 31 Aug 2026
Company statement
Press release reviewed: CL04183 has reached readiness to file for a first study in people, which the company is preparing to start in 2027 in cancers with faulty p53. It does not state that an application was filed or accepted, and does not name a country.
76
Peter de Keizer on cells in hibernation ↗
UMC Utrecht · Research stories · Checked 23 Sep 2026
Context and reviews
Indexed excerpt reviewed: developer commentary on later-generation clinical ambitions, not a dosing or trial record.
77
The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI ↗
Bourgeois B, Madl T, de Keizer PLJ et al. · Nature Communications · 2025 · PMID 40593617
Purified-protein research
Original full text reviewed: isothermal titration calorimetry giving a dissociation constant of 400 ± 280 nanomolar for p53 residues 1 to 94 and 18.5 ± 3.6 micromolar for unphosphorylated TAD2, with no binding to the p53 DNA-binding domain.
Disclosure: partly funded by the company developing the successor peptides; two authors held shares in it and the authors declared related patent interests.
78
Transcription-independent induction of rapid-onset senescence is integral to healing ↗
Valdivieso K et al. · Nature Cell Biology · 28 May 2026 · PMID 42209725
Cell / animal research
Original full text reviewed: suppressing the rapid senescence response early after a mouse skin wound delayed closure, while suppressing it later did not. FOXO4-DRI was not used.
79
An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA ↗
Demaria M, Ohtani N, Youssef SA et al. · Developmental Cell · 11 Dec 2014 · PMID 25499914
Cell / animal research
Original abstract reviewed. FOXO4-DRI was not used; this establishes a biological cost of clearing senescent cells. The paper received an editorial expression of concern in 2026, which is why a more recent independent study is cited alongside it.
80
Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 ↗
Cheng N, Kim K-H, Lau LF · JCI Insight · 16 Jun 2022
Cell / animal research
Original full text reviewed. Neither FOXO4-DRI nor any FOXO4-targeting peptide was used.
81
Epithelial innate immunity mediates tubular cell senescence after kidney injury ↗
Jin H, Zhang Y, Ding Q et al. · JCI Insight · 2019
Cell / animal research
Original full text reviewed: senescent cells fell after folic-acid kidney injury while scarring, infiltration and tubule damage did not improve. The peptide dosing detail sits in an inaccessible supplement.
82
Innate Immune Signaling Contributes to Tubular Cell Senescence in the Glis2 Knockout Mouse Model of Nephronophthisis ↗
Jin H, Zhang Y, Liu D et al. · The American Journal of Pathology · 2020 · PMID 31676329
Cell / animal research
Indexed excerpt reviewed: kidney damage, scarring, inflammation and cell death improved while tubular senescence did not change.
83
Anti-senescence peptides and uses (WO2025049883A1) ↗
WIPO / PCT record indexed by Google Patents · 2025
Patent application
Application text reviewed: a small mouse comparison, about three animals per group, at 5 mg per kg into the abdominal cavity with three administrations about 48 hours apart. Some blood-count effects did not reproduce and kidney markers varied.
84
FOX04 protocol ↗
r/Biohacking · Reddit · May 2026
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
85
Thinking about running FOXO4-DRI ↗
r/ResearchCompounds · Reddit · 15 Apr 2026
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
86
Any FOXO4-DRI experiences here? ↗
r/Peptidesource · Reddit · Checked 23 Sep 2026
Community account
Thread read: a Dutch-language report of severe, sustained high blood pressure within one to three days of two 100 microgram injections, in someone already taking a blood-pressure medicine who took extra during the episode and had paused several supplements before the course. Blood pressure had settled by day ten; tingling and hot flushes had not.
87
Bizarre FOXO4-DRI product ↗
Longecity forum · 17 May 2021
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
88
TGA warning on the risks of importing unapproved peptide products ↗
Therapeutic Goods Administration · Safety alert · 2026
Regulatory source
Alert reviewed: a general warning about importing unapproved peptide products. FOXO4-DRI is not named.
89
Geneesmiddeleninformatiebank search for FOXO4-DRI ↗
Medicines Evaluation Board · Netherlands · Searched 23 Sep 2026
Regulatory source
Register searched by a research assistant rather than opened by the lead: no FOXO4-DRI entry returned. The Netherlands is where the peptide was developed.
90
WADA publishes the 2027 Prohibited List ↗
World Anti-Doping Agency · Published 2026 · In force 1 Jan 2027
Regulatory source
List text searched: FOXO4-DRI is not named. The 2027 list adds “peptides” to the examples given under category S0.
91
Any FOXO4-DRI experiences? ↗
r/PeptideForum · Reddit · Checked 23 Sep 2026
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
92
Guidelines for minimal information on cellular senescence experimentation in vivo ↗
Ogrodnik M, Carlos Acosta J, Adams PD et al. · Cell · 8 Aug 2024
Expert guideline
Guidance reviewed: no single marker is sufficient to detect cellular senescence in a living body.
93
Characterization of human senescent cell biomarkers for clinical trials ↗
Aging Cell · 17 Jan 2025
Human report
Original full text reviewed: p16 variants in sampled T cells are described as potential biomarkers for future trials, not as a validated clinical test.
94
Has anyone tried FOX04-DRI? ↗
r/Peptides · Reddit · 20 Sep 2023
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
95
FOXO4-DRI: notes from 12 days past three 28 mg administrations ↗
Rapamycin.news forum · 30 Aug 2026
Community account
Thread read: three administrations of 28 mg 48 hours apart, with skin observations at about ten days and planned blood tests that had not been posted by the cutoff.
96
Anyone had results with FOXO4-DRI? ↗
Longecity forum · 26 Sep 2020
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
97
Senolytic therapy, what are you doing? ↗
Rapamycin.news forum · Checked 23 Sep 2026
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
98
Has anybody experimented with FOXO4-DRI by chance? ↗
r/Peptides · Reddit · 21 Dec 2023
Community account
Public thread read; the accounts in it are self-reports and no product in them was independently verified.
99
Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial ↗
Farr JN, Atkinson EJ, Achenbach SJ et al. · Nature Medicine · 2 Jul 2024 · NCT04313634
Human trial
Publication record and abstract reviewed: 60 postmenopausal women over 20 weeks; the main bone-turnover measure did not differ between groups (median −4.1% against −7.7%, P=0.611).
100
Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study ↗
Justice JN, Nambiar AM, Tchkonia T et al. · EBioMedicine · 5 Jan 2019
Human report
Original abstract reviewed: an open-label feasibility pilot in 14 people, not a controlled efficacy trial.
101
Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease ↗
Hickson LJ, Langhi Prata LGP, Bobart SA et al. · EBioMedicine · 18 Sep 2019
Human report
Original abstract reviewed: an uncontrolled tissue-marker study in 9 people.
102
SPRYCEL (dasatinib) prescribing information ↗
Bristol-Myers Squibb · FDA-approved label on DailyMed · Checked Sep 2026
Official label
Label reviewed for the approved indications. There is no senolytic indication.
103
Results from a randomized clinical trial evaluating the senolytic fisetin in knee osteoarthritis ↗
Tashman JW et al. · Orthopaedic Research Society 2025 annual meeting abstract · NCT04210986
Human trial
Conference abstract reviewed: 74 randomized, 12 months; adverse-event comparisons all above P=0.5 and the cartilage scan measure showed no difference. A full trial report was not located.
104
Senolytic drugs attenuate osteoarthritis-related articular cartilage degeneration (NCT04210986) ↗
University of Pittsburgh · ClinicalTrials.gov · Checked 23 Sep 2026
Study registry
Registry record checked for the design, arms and schedule of the fisetin knee-osteoarthritis trial.
105
Questions and answers on dietary supplements ↗
US Food and Drug Administration · Checked 23 Sep 2026
Regulatory source
Guidance reviewed: dietary-supplement ingredients are not approved by the FDA before marketing, and supplement status is not an efficacy finding.
106
TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis ↗
Blood · 30 Jun 2026 · PMID 42378247 · NCT04472598
Human trial
Original abstract reviewed: 252 participants; 63.2% against 31.5% reached the spleen-volume measure at week 24 (P<0.0001), with grade 3 or 4 low platelet counts in 54.0% against 19.2%. This is a cancer outcome, not evidence of senescent-cell clearance.
107
Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease ↗
Roberts AW, Seymour JF, Brown JR et al. · Journal of Clinical Oncology · 2012 · PMID 22184378
Human trial
Original abstract reviewed: low platelet counts were the dose-limiting toxicity.
108
FDA orphan drug designation record: navitoclax ↗
US Food and Drug Administration · Orphan Drug Designations database · Checked 23 Sep 2026
Regulatory source
Record checked: navitoclax is not approved for the designated indication. Orphan designation is not marketing approval.
109
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial ↗
Karaa A, Bertini E, Carelli V et al. · Neurology · 18 Jul 2023 · PMID 37268435 · NCT03323749
Human trial
Original full text reviewed: 218 participants over 24 weeks; the six-minute walk difference was −3.2 metres (95% CI −18.7 to 12.3, P=0.69) and the fatigue measure was also not met.
110
Drug Trials Snapshots: Forzinity (elamipretide) ↗
US Food and Drug Administration · Approved 19 Sep 2025
Regulator / approval record
Approval summary reviewed: accelerated approval to improve muscle strength in adults and children with Barth syndrome weighing at least 30 kg, given once daily by subcutaneous injection. It is not approved for primary mitochondrial myopathy or general mitochondrial support.
111
Benzyl isothiocyanate provokes senolysis by targeting AKT in senescent IPF fibroblasts and reverses persistent pulmonary fibrosis in aged mice ↗
Wang R, Zhang Y, Wang J et al. · Frontiers in Pharmacology · 2025 · PMID 40385483
Cell / animal research
Original full text reviewed: FOXO4-DRI used at 25 micromolar for 48 hours as a comparator. The reported mouse reversal belongs to a different compound, not to FOXO4-DRI.
112
Expression of concern: An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA ↗
Developmental Cell · 29 May 2026
Editorial notice
Notice reviewed. It does not state that the finding is withdrawn or refuted, and an independent later study reports a comparable result.
113
FOXO4-DRI alleviates age-related testosterone secretion insufficiency via targeting senescent Leydig cells in aged mice ↗
Liu G, Yang X, Li T · Fertility and Sterility · September 2020 · 114(3 Suppl):e362-e363 · ASRM congress abstract · not indexed in PubMed
Conference abstract
Conference abstract, treated as low-grade evidence: it is not a peer-reviewed full paper and has no PubMed record. Original abstract reviewed on the publisher's page. It reports that the aged mice received FOXO4-DRI at 5 mg per kg into the abdominal cavity every other day for three doses, that CK, CK-MB, ALT, AST, creatinine and blood urea nitrogen did not differ significantly (P>0.05), and that seminal-vesicle weight relative to body weight fell significantly (P<0.05) while testis weight relative to body weight did not change significantly (P>0.05). Same schedule and same research group as source [19], so it overlaps that experiment rather than adding an independent dataset.

Updates and corrections

Published September 23, 2026. This is the first version of this guide in the Definitive Guide format. Because FOXO4-DRI is designed to kill cells, because its selectivity for senescent cells failed in several human-cell experiments, and because the only repeated-dose animal toxicity study found liver-enzyme and platelet changes, the guide shows study and website amounts with a safety warning instead of a typical protocol. The date describes this version, not a fresh check of every source.

Updated September 27, 2026. A search of Elsevier content that PubMed does not index, including congress-abstract supplements, added one source: a 2020 congress abstract from the same research group as the aged-mouse testosterone study, reporting that six blood markers of muscle, heart, liver and kidney function or injury did not differ significantly after three injections in aged mice, and that seminal-vesicle weight relative to body weight fell, which the abstract does not explain. It is a meeting abstract, so the guide treats it as low-grade evidence that overlaps a study already cited, not as a safety finding.

Corrections carried over from the previous version of this page. The sequence has 46 amino acids, not 49, and its molecular mass is 5,358.2 daltons, not 4.8 or 1.5 kilodaltons. The CAS registry number previously attached to FOXO4-DRI belongs to a different peptide, MOTS-c, and has been removed. The 2021 cartilage study is by Huang and colleagues, the 2025 keloid study appeared in Communications Biology, and the naturally aged mouse comparison used p16::3MR mice older than 110 weeks. Statements that FOXO4-DRI is "not approved anywhere" have been rewritten to name the registers actually searched.

Found an error or a relevant study we missed? Report a correction with the guide title, the specific passage and a supporting source if available. Please leave out personal health records. See our editorial policy for how we handle attribution, evidence limits and corrections.

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