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Animal data onlyNot FDA approved

FOXO4-DRI

Also known as: FOXO4 DRI · FOXO4-D-Retro-Inverso · FOXO4 peptide · FOX04-DRI

Updated 26 sources

A synthetic senolytic: a 46 amino acid D-retro-inverso peptide that makes senescent cells self-destruct by blocking FOXO4 from holding p53. In a 2017 mouse study it restored fur, fitness and kidney function in old mice. Nobody has tested it in people. Users run short pulses of a few doses every other day, then stop for months.

Quick facts

Half-life
  • Not published for people or animals. D-amino acids resist protein-cutting enzymes, which guides say may extend its activity.
Routes
  • Subcutaneous injection
Forms
  • Vial (powder)
Reported dose ranges
  • 1 to 25 mg (subcutaneous injection)
  • 250 to 500 mcg (subcutaneous injection)
Vial sizes
  • 10 mg
Chemistry
  • 5,358.15 g/mol · C228H388N86O64 · CAS 2460055-10-9
FDA status
  • Not FDA approved
WADA
  • Not confirmed

What people use FOXO4-DRI for

  • Clearing senescent (zombie) cells as a once or twice a year longevity reset
  • Hair, skin texture and a younger look, based on the fur regrowth in old mice
  • Energy and recovery, the top picked benefits in one app's self-reports
  • Low testosterone with age, from mouse work on aging testes
  • First step of a longevity sequence, followed by epitalon, GHK-Cu, MOTS-c or NAD+

How it is thought to work. Senescent cells survive because FOXO4 binds p53 in the nucleus and stops it from triggering cell death. FOXO4-DRI copies the part of FOXO4 that binds p53, so it competes for that spot; p53 leaves the nucleus and the senescent cell self-destructs. Healthy cells are mostly spared. The D-amino acid build resists breakdown, and a TAT tail carries it into cells.

FOXO4-DRI dosing

7 protocols from studies, guides and community reports, grouped by goal. Tap a source badge to see where a number came from.

Injected7

Short senolytic pulse

Amount
2 to 10 mg
How often
Every other day for 3 doses
Route
SubQ, vial (powder)
Cycle
One course of 3 doses over 5 to 6 days
Rest
Course repeated 1 to 3 times a year
Timing and details

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First course, low dose

Amount
1 mg
How often
Every other day for 3 doses
Route
SubQ, vial (powder)
Cycle
One course of 3 doses
Timing and details

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Extended alternate-day course

Amount
1 to 3 mg
How often
Every other day, 5 doses or 10 to 20 days
Route
SubQ, vial (powder)
Cycle
10 to 20 days
Rest
At least 4 to 6 months before the next course
Timing and details

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Higher-dose pulse

Amount
3 to 25 mg
How often
Every other day for 3 to 6 doses
Route
SubQ, vial (powder)
Cycle
3 to 6 doses per course
Rest
Courses repeated 1 to 3 times a year
Timing and details

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Three days in a row

Amount
1 to 2 mg
How often
Once daily for 3 consecutive days
Route
SubQ, vial (powder)
Cycle
3 days
Rest
Months off; most users run it 2 to 4 times a year at most
Timing and details

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Five nightly doses (one blogger)

Amount
1 mg
How often
Once a night for 5 nights
Route
SubQ, vial (powder)
Cycle
5 days
Timing and details

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Daily low-dose ladder (outlier)

Amount
250 to 500 mcg
How often
Once daily, stepping up every 4 weeks
Route
SubQ, vial (powder)
Cycle
8 to 16 weeks
Titration (3 steps) and details

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Doses shown are what sources report, labelled by origin. Not medical advice.

Full FOXO4-DRI dosage guideEvery titration step in syringe units, missed doses and how to mix.

Vial strengths and syringe units

Every FOXO4-DRI vial size with the water volumes sources use. Units are what to draw on a U-100 insulin syringe, worked out exactly.
FOXO4-DRI: concentration and U-100 syringe units for each vial size and water volume
WaterStrength1 mgdose, units2 mgdose, units3 mgdose, units
10 mg vial
1 mLCompetitor guide10 mg/mL100.1 mL200.2 mL300.3 mL
2 mLCompetitor guide5 mg/mL200.2 mL400.4 mL600.6 mL
3 mLCompetitor guide3.333 mg/mL300.3 mL600.6 mL900.9 mL
Units are on a U-100 insulin syringe (100 units = 1 mL). U-50 and U-30 barrels read the same units.Water volumes from

Doses shown are what sources report, labelled by origin. Not medical advice.

Calculate with this peptideYour vial, your water, your dose: FOXO4-DRI in syringe units, with the math shown.

FOXO4-DRI side effects

What trials and labels report, kept apart from what users and guides report. Frequencies are worded as each source states them.

Reported in studies and labels1

From clinical trials and regulatory documents.

  • Worse pulmonary hypertension in animal models

    Animal finding: mice prone to high lung blood pressure given FOXO4-DRI or another senolytic did worse

Reported by users and guides6

From community reports and dosing guides. Not measured rates.

  • Flu-like symptoms

    The most often reported effect, usually 24 to 48 hours after an injection and lasting 1 to 3 days

    How people manage it

    • Guides suggest rest and fluids on course days; one says to stay well hydrated because clearance produces debris.
  • Fatigue

    The second most common report; about 24 to 48 hours

    How people manage it

    • Some users take days off training during and after a course; one blogger took 10 days off the gym.
  • Injection-site soreness, redness or burning

    Common; one guide says soreness can last several days, longer than with most peptides

    How people manage it

    • Rotate sites between the abdomen and thigh.
  • Joint aches or muscle soreness

    Reported for a day or two after dosing

  • Headache

    Less common; reported more at higher doses (5 mg a day and up)

  • Nausea

    Less common, usually mild

All 9 FOXO4-DRI side effects and how people manage themEvery management tip, who should not use it, and side-effect questions.

Who should avoid it

  • Pulmonary hypertensionCondition

    Clearing senescent lung blood vessel cells with FOXO4-DRI or ABT263 worsened pulmonary hypertension in mouse models.

  • Active cancerCondition

    Listed as a reason to avoid by a dosing guide.

  • ImmunosuppressantsSubstance

    A guide says not to combine them unless a doctor supervises.

  • Other senolytics at the same timeSubstance

    Guides run FOXO4-DRI alone and do not overlap it with other senolytics.

  • Pregnancy or breastfeedingCondition

    Listed as a reason to avoid by guides.

  • Under 18Condition

    Listed as a reason to avoid by a guide.

  • Poor kidney or liver functionCondition

    One guide warns that a large wave of cell clearance could strain these organs and suggests a blood panel at baseline and one week after the course.

Storage

Powder (before mixing)

Temperature
-20 °C

Freezer at -20 C for long-term storage, colder is better. One guide says the fridge or freezer both work.

Mixed vial

Temperature
2 to 8 °C
Use within
28 to 30 days

Fridge, 2 to 8 C, never frozen, kept dark. Most guides say use within 28 days; one says 28 to 30. Two others give no day count. Nobody has tested research vials.

Mixed with: Bacteriostatic water

Mixing. 2 mL suits the 1 to 2 mg community pulses; 3 mL suits the small daily ladder. One guide says saline may cause precipitation. The solution should be clear; discard it if cloudy.

Stacks people report

Combinations from guides and community posts, with the reason given.
  • Epitalon

    Run after, not with. Guides clear senescent cells first, then start epitalon 4 days to 2 weeks after the last FOXO4-DRI dose, often 5 to 10 mg a day for 10 days. No study has tested the sequence.

  • MOTS-c

    Sequenced after a rest week: one guide follows the senolytic phase with MOTS-c 5 to 10 mg 3 times a week.

  • GHK-Cu

    Started 1 to 2 weeks after the course, at 1 to 2 mg a day in one guide.

  • BPC-157

    One guide waits about two weeks after the course before an optional BPC-157 run. Another says to pause all regenerative peptides for at least a week either side of a senolytic course.

  • NAD+

    Part of longevity sequences, started after the two-week gap.

  • Glutathione

    Listed with NAD+ in a niche anti-aging stack on one community roundup.

  • Retatrutide

    The compound most often co-logged with FOXO4-DRI in one app's self-reports (14 co-reports), ahead of MOTS-c (7). No reason for the pairing is given.

Compare FOXO4-DRI

Evidence and legal status

Evidence: animal data only

Animal and cell work only. Baar et al. 2017 restored fur density, fitness and kidney function in fast-aging and old mice, at 5 mg per kg given 3 times every other day. Other groups used it in aged mouse testes (2020, 2024) and mouse lung fibrosis (2023). A 2023 study found it worsened pulmonary hypertension in mice. The headline rejuvenation result has no independent replication, and no human trial is registered.

FDA and WADA

Not FDA approved

No approval, no trial program and not on FDA's compounding lists.

Not FDA approved. Not on FDA's 503A bulk substance lists (categories 1 to 3, May 14, 2026 update) and not on the Category 2 safety-risk page. No clinical trial is registered. Sold as a research chemical.

Not named on the WADA 2026 Prohibited List. The S0 class bans any substance with no human approval, including drugs in pre-clinical development, which on its plain wording covers FOXO4-DRI. No anti-doping body addresses it directly.

WADA: Not confirmed

FOXO4-DRI questions

What is FOXO4-DRI?

A synthetic peptide built from D-amino acids in reverse order (a D-retro-inverso design) and fused to a cell-entry sequence from HIV-TAT. It was designed in 2017 to break the bond between FOXO4 and p53 inside senescent cells, which pushes those cells to self-destruct.

What does FOXO4-DRI do?

In mice it cleared senescent cells, countered chemotherapy toxicity and restored fur density, fitness and kidney function in fast-aging and naturally aged animals. In aged mice it also eased low testosterone and improved sperm quality. None of this has been tested in people.

What is the FOXO4-DRI dose?

No human dose exists. Community courses copy the mouse schedule: 3 doses every other day, most often 2 mg each, with reported ranges from 1 mg to 10 mg and some guides listing up to 25 mg. Then people stop for months.

How was FOXO4-DRI dosed in the mouse study?

In Baar et al. 2017: 5 mg per kg, 3 doses every other day (days 1, 3 and 5), into a vein for the chemotherapy (doxorubicin) mice and into the abdomen for naturally aged mice. The aged mice were assessed 30 days after the injections. It is the only published whole-animal regimen, it was never tested in people, and mouse doses do not carry over to humans by body weight.

Why not just scale the mouse dose to a human?

Guides that convert by body surface area get roughly 25 mg per dose for a 60 kg adult or about 28.5 mg for 70 kg, far above what most users inject. One guide warns the conversion carries large uncertainty, and no human study has checked any of it.

How often can you repeat a FOXO4-DRI course?

Guides say 1 to 3 courses a year, with at least 4 to 6 months between them as the community consensus.

Why do people feel flu-like after FOXO4-DRI?

It is the most reported effect, usually a day or two after a dose. Guides attribute it to cleared cells and the debris they leave. That is a guess; nobody has measured senescent cell burden before and after in a user.

How much bacteriostatic water for a 10 mg vial?

Guides use 1, 2 or 3 mL. 2 mL gives 5 mg per mL, so a 2 mg dose is 40 units; 3 mL suits small daily doses.

How many units is 2 mg of FOXO4-DRI?

40 units on a U-100 insulin syringe when a 10 mg vial is mixed with 2 mL. With 1 mL it is 20 units.

How long does mixed FOXO4-DRI last?

Guides say about 28 days in the fridge at 2 to 8 C. Since a course is only 3 to 5 doses, most people finish a vial well inside that.

What is the half-life of FOXO4-DRI?

Never published. D-amino acids resist the enzymes that break down normal peptides, so guides expect it to last longer than most. In cell studies the peptide was still detectable inside senescent cells 72 hours later.

Has FOXO4-DRI been tested in humans?

No. ClinicalTrials.gov lists no FOXO4-DRI study. Human data are limited to cells in a dish, such as expanded cartilage cells where it removed more than half of the cells in the most senescent batches.

Is FOXO4-DRI safe?

In the 2017 mice it looked well tolerated: no change in body weight, platelets or heart tissue. One later mouse study found senolytics including FOXO4-DRI worsened pulmonary hypertension. Human safety is unknown.

Is FOXO4-DRI FDA approved?

No. It is not approved and is not on FDA's 503A bulk substance lists for compounding (May 2026 update). It is sold as a research chemical.

Is FOXO4-DRI banned in sport?

It is not named on the WADA 2026 list. The S0 class bans any substance without human approval, including drugs in pre-clinical development, which on its plain wording covers FOXO4-DRI.

Can you stack FOXO4-DRI with other peptides?

Guides sequence instead of stacking: run FOXO4-DRI alone, wait 1 to 2 weeks, then start epitalon, GHK-Cu, MOTS-c or NAD+.

Does FOXO4-DRI help hair?

In fast-aging mice it brought back fur density. No human hair data exist.

What do app users log for FOXO4-DRI?

One app's anonymous logs (28 reporters) show most doses at 2 mg or more per injection, with recovery and energy as the top picked benefits. These are self-reports, not evidence.

Ask about FOXO4-DRI

Answers come from this site's pages only, with a link to each source.

Sources

26 sources, each checked by date. Record updated Oct 24, 2026. Numbers are restated in our own words and labelled by where they came from.

Reference work1

  1. FOXO4-DRIWikipedia · checked Oct 24, 2026

Vendor guide1

  1. FOXO4-DRI (10mg) product listingVendor product page · checked Oct 24, 2026

Competitor guide7

  1. FOXO4-DRI 10 mg vial dosage protocolpeptidedosages.com · checked Oct 24, 2026
  2. FOXO4-DRI quick start protocolpeptidedosingprotocols.com · checked Oct 24, 2026
  3. FOXO4-DRI dosage guide: senolytic protocolspeptidewiki.co · checked Oct 24, 2026

Community-reported5

  1. FOXO4-DRI community protocols and anecdotal reportspeptideprotocolwiki.com, via a competitor guide · checked Oct 24, 2026
  2. FOXO4-DRI: what the research actually showspeptibase.dev, via a competitor guide · checked Oct 24, 2026
  3. FOXO4-DRI: the senolytic peptide that restored old mice in one studypeptidebreakdown.com, via a competitor guide · checked Oct 24, 2026