FOXO4-DRI
FDA APPROVAL PENDING
Preclinical
Longevity
FOXO4-DRI
46
Amino acids
Molecular weight
Peptide
Type
FOXO4-DRI is a synthetic all-D-amino acid retro-inverso senolytic peptide designed to selectively eliminate senescent cells by blocking the FOXO4–p53 protein interaction. By disrupting this interaction, p53 is redirected from the nucleus to mitochondria, triggering apoptosis specifically in senescent cells while sparing healthy tissue. It is used in preclinical longevity research and has demonstrated the ability to restore tissue function, fur density, and physical fitness in aged animal models.
Top researched benefits
Overview of FOXO4-DRI
FOXO4-DRI competes with endogenous FOXO4 for binding to p53, disrupting the FOXO4–p53 survival complex that senescent cells rely on to evade apoptosis. This causes nuclear export of p53 and its translocation to mitochondria, initiating the intrinsic apoptosis pathway selectively in senescent cells.
antiaging
- Selectively induces apoptosis in senescent cells while sparing healthy tissue.
- Restores tissue homeostasis and function in naturally aged animal models.
- Improved fitness, mobility, and physical appearance in aged mice.
organ function
- Restored renal function in aged and fast-aging mouse models.
- Improved testicular microenvironment and testosterone secretion in aged mice.
- Removes senescent chondrocytes, potentially benefiting joint health.
chemoprotection
- Neutralizes doxorubicin-induced chemotoxicity by clearing treatment-induced senescent cells.
Typical Dose
250–500mcg per injection, titrated over time
Frequency
once daily via subcutaneous injection
Cycle Duration
8–16 week graduated protocol (250mcg weeks 1–4, 375mcg weeks 5–8, 500mcg weeks 9–16)
Storage
Lyophilized: -20°C for up to 1 year, -80°C for up to 2 years. Reconstituted: 2–8°C for up to 28 days; avoid freeze-thaw cycles.
Chemical Makeup
Key benefits
Selectively eliminates senescent 'zombie' cells by inducing apoptosis via FOXO4–p53 axis disruption without harming healthy proliferating cells
Restored fur density, renal function, and physical fitness in naturally aged mice in landmark 2017 Baar et al. Cell study
Improved endothelial cell function and delayed vascular aging by clearing senescent endothelial cells in aged mouse aorta
Alleviated age-related testosterone deficiency by targeting senescent Leydig cells and improving the testicular microenvironment
Community interest
This peptide is still gaining traction in the community.
Senolytic Peptide | Longevity & Anti-Aging
This overview is informational and based on aggregated descriptions from studies and user reports.
Was it helpful?YesNoFOXO4-DRI Molecular Information
View the scientifc details of FOXO4-DRI.
46
Amino Acids
FOXO4-DRI
Leu
Leu
Position 1
Thr
Thr
Position 2
Leu
Leu
Position 3
Arg
Arg
Position 4
Lys
Lys
Position 5
Glu
Glu
Position 6
Pro
Pro
Position 7
Ala
Ala
Position 8
Ser
Ser
Position 9
Glu
Glu
Position 10
Ile
Ile
Position 11
Ala
Ala
Position 12
Gln
Gln
Position 13
Ser
Ser
Position 14
Ile
Ile
Position 15
Leu
Leu
Position 16
Glu
Glu
Position 17
Ala
Ala
Position 18
Tyr
Tyr
Position 19
Ser
Ser
Position 20
Gln
Gln
Position 21
Asn
Asn
Position 22
Gly
Gly
Position 23
Trp
Trp
Position 24
Ala
Ala
Position 25
Asn
Asn
Position 26
Arg
Arg
Position 27
Arg
Arg
Position 28
Ser
Ser
Position 29
Gly
Gly
Position 30
Gly
Gly
Position 31
Lys
Lys
Position 32
Arg
Arg
Position 33
Pro
Pro
Position 34
Pro
Pro
Position 35
Pro
Pro
Position 36
Arg
Arg
Position 37
Arg
Arg
Position 38
Arg
Arg
Position 39
Gln
Gln
Position 40
Arg
Arg
Position 41
Arg
Arg
Position 42
Lys
Lys
Position 43
Lys
Lys
Position 44
Arg
Arg
Position 45
Gly
Gly
Position 46
Molecular Weight
5358.06DaChain Length
46Amino AcidsType
PeptideFOXO4-DRI Protocols
Subcutaneous injection is the only documented route for FOXO4-DRI in human research use, providing sufficient systemic bioavailability to disrupt the FOXO4-p53 interaction in senescent cells. Administration follows a pulsed 'hit-and-clear' senolytic model — typically a 2-week course of 5-days-on/2-days-off dosing at 1 mg, or a 6-day every-other-day pulse at higher doses — repeated 2–3 times per year with 3–6 months between cycles to allow immune clearance of apoptotic debris. A high-dose variant at 3 mg every other day for 6 days has been reported in longevity self-experimentation circles (notably documented by Ben Greenfield), though no human clinical trial data supports any specific protocol.
| Goal | Dosage | Frequency | Route |
|---|---|---|---|
| Reduce senescent cell burden with a conservative 2-week pulse to selectively trigger apoptosis in FOXO4-p53-dependent senescent cells while minimising off-target effects | 1 | 5 period | SubQ |
| Achieve greater senescent cell elimination during a concentrated 6-day cycle using a higher per-dose exposure, repeated 1–3 times per year with extended rest between cycles | 3 | 3 period | SubQ |
| Sustain low-burden senescent cell clearance throughout the year via brief alternating-day pulses administered quarterly to support general tissue homeostasis and longevity | 1 | 3 period | SubQ |
| Clear senescent chondrocytes from joint tissue to reduce inflammation and support cartilage integrity, using a short conservative cycle consistent with in vitro chondrocyte research | 1 | 4 period | SubQ near affected joint |
| Reduce senescent Leydig cell burden in the testes to support age-related testosterone decline, based on murine data showing improved steroidogenic function after FOXO4-DRI treatment | 2 | 3 period | SubQ |
| Achieve gradual senescent cell reduction over a longer administration window using every-other-day dosing for 20–30 days, suited to those seeking a slower-onset senolytic effect with lower per-dose exposure | 1 | 10 period | SubQ |
Reconstitution Instructions
Materials needed:
Steps to reconstitute
- Remove the FOXO4-DRI vial (10 mg lyophilized) from the freezer and allow it to reach room temperature for 15–20 minutes before reconstituting
- Draw 2 mL of bacteriostatic water into an insulin syringe (0.5–1 mL, 29–31 gauge) — 2 mL yields 5 mg/mL concentration; 1 mg dose then equals 0.2 mL (20 units on a U-100 scale)
- Wipe the rubber stopper of the peptide vial with an alcohol swab and allow to air dry for 30 seconds
- Insert the needle at an angle and inject the bacteriostatic water slowly down the inside wall of the vial — do not aim directly at the peptide cake
- Remove the syringe and gently swirl the vial for 30–60 seconds until fully dissolved — do not shake or vortex
- If solution remains cloudy, allow it to sit refrigerated for 5–10 minutes and swirl again before use
- Store reconstituted vial refrigerated at 2–8°C and use within 14–21 days; do not refreeze
- For each injection, draw the target dose volume using a fresh insulin syringe (0.5–1 mL, 29–31 gauge, 0.5 inch needle)
- Clean the injection site (abdomen, thigh, or upper arm) with an alcohol swab and allow to dry
- Pinch a fold of subcutaneous fat and insert the needle at 45–90°, inject slowly without aspiration, then remove and apply light pressure
- Rotate injection sites at least 1 inch apart on each administration to avoid tissue irritation
FOXO4-DRI Cycle
The FOXO4-DRI Cycle section explains how long a typical cycle lasts and what to expect during each phase. Over time, your body can become less responsive with continuous use.
Taking breaks between cycles may help maintain effectiveness and support better overall results.
- Week 0-0
- Senescent cell apoptosis initiated
- Week 0-0
- Clearance of senescent cells
- Week 0-0
- Tissue regeneration and functional improvements
- Week 0-0
- Sustained benefits with periodic treatment
Dosing tools
FOXO4-DRI Peptide Dosage Calculator
Calculate peptide doses with our visual syringe guide.
mg
Enter the total amount of peptide in the vial in milligrams (as stated on the label).
The dose you want to inject per administration, in mcg or mg.
1,000 mcg = 1 mg
1 mL
2 mL
3 mL
5 mL
Custom
Volume of bacteriostatic water you add to reconstitute the powder. Use BAC water for preservation.
Injection Results
Based on your vial and dilution inputs.
FOXO4-DRI
SINGLE COMPOUNDVolume per injection
0.05
mL
Concentration
10.00
mg/mL
Doses per vial
20
doses
Total injections per vial
20 injections
How it works
Based on a 10 mg FOXO4-DRI vial diluted with 1 mL of bacteriostatic water, each 500 mcg injection equals 0.05 mL.
1mL / 100 units
5 units
0.050 mL
Reference Guide
Dosing Cycle
- Peptide
- FOXO4-DRI
- Dosing
- 250–500mcg per injection, titrated over time
- Dosing Frequency
- once daily via subcutaneous injection
- Cycle Duration
- 8–16 week graduated protocol (250mcg weeks 1–4, 375mcg weeks 5–8, 500mcg weeks 9–16)
- Storage
- Lyophilized: -20°C for up to 1 year, -80°C for up to 2 years. Reconstituted: 2–8°C for up to 28 days; avoid freeze-thaw cycles.
Note: Triple agonist; microdose for fewer side effects
Reconstitution Tips
- Use bacteriostatic water (BAC) — contains 0.9% benzyl alcohol for preservation
- Inject water slowly — aim down the vial wall, not directly onto powder
- Never shake — gently swirl or roll the vial until dissolved
- Store properly — refrigerate at 2-8°C after reconstitution
- Use within 28 days — most reconstituted peptides remain stable for about 4 weeks
- Keep sterile — always clean vial tops with alcohol before drawing
Peptide Interactions
Research suggestions of FOXO4-DRI interactions with other common peptides and substances.
Cognitive
hum
Longevity
Humanin
COMPATIBLE
Different mechanisms; Humanin protects healthy cells while FOXO4-DRI clears senescent ones.
Side effects
Contraindications
Not yet approved for human use
Pregnancy or breastfeeding
Unknown safety in immunocompromised individuals
Active cancer (theoretical - consult oncologist)
Stop signs
Allergic reactions
Unexpected adverse effects
Bad signs
Comments
0.0
0 reviews
5
4
3
2
1
No comments yet
Be the first to share your experience. Your review helps others make more informed decisions.
Frequently asked questions
What is a peptide dosage calculator?
A peptide dosage calculator is a free tool that converts your vial size, bacteriostatic water volume, and target dose into an exact syringe draw volume. Instead of doing the reconstitution math by hand, you enter three inputs and instantly get the concentration of your solution and how many milliliters or syringeunits to draw. This calculator works for single peptide compounds and multi-peptide blends.
How do I calculate peptide dosage from a vial?
To calculate your peptide dose, divide the total peptide content of your vial in micrograms by the volume of bacteriostatic water you added in milliliters. This gives you your solution concentration in mcg/mL. Then divide your target dose by that concentration to get your draw volume. For example, a 5mg (5,000 mcg) vial reconstituted with 2mL of BAC water gives a concentration of 2,500 mcg/mL. A 250 mcg dose would require drawing 0.1mL. This calculator automates all of those steps instantly.
How much Bacteriostatic water should I add to a peptide vial?
Most people add 2mL to 3mL of bacteriostatic water per vial, but the right amount depends on the dose you want to draw and the syringe size you are using. Adding 1mL to a 5mg vial gives you a concentration of 5,000 mcg/mL, making each dose very small in volume. Adding 2mL gives you 2,500 mcg/mL, which is easier to measure on a standard insulin syringe. A general guideline is to choose a volume that puts your typical dose somewhere between 10 and 30 units on a U-100 syringe. Use the calculator above to test different water volumes and find what works for your dose.
How are peptides different from proteins?
Both are made of amino acids, but peptides are much smaller than proteins. Because of their tiny size, peptides can act like tiny messengers in the body, sending specific signals to your cells to tell them exactly what to do.
FOXO4-DRIResearch References
FOXO4-DRI is a preclinical compound
FOXO4-DRI
FOXO4-DRI is a preclinical compound
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis
FOXO4-DRI restored fitness, fur density, and renal function in aged mice using 5 mg/kg IP, 3 doses on alternate days. Well-tolerated under therapeutic conditions.
n.d.
An Example of Senolytic Self-Experimentation with FOXO4-DRI
Self-experimenters have translated the mouse protocol to ~25 mg per injection subcutaneously, 3 doses every other day, for 75-100 mg total per treatment cycle.
n.d.
FOXO4-DRI Alleviates Age-Related Testosterone Secretion Insufficiency
FOXO4-DRI improved testicular microenvironment and testosterone secretion by clearing senescent Leydig cells.
n.d.
FOXO4-DRI Removes Senescent Cells from Human Chondrocytes
Removed >50% of senescent chondrocytes without affecting healthy early-passage cells.
n.d.
The Disordered p53 Transactivation Domain is the Target of FOXO4-DRI
Structural analysis revealed FOXO4-DRI binds disordered p53TAD2, forming transiently folded complex.
n.d.
Calculate peptide dosages
Learning how to calculate a peptide dose? Use our beginner-friendly peptide dosage, blend, and accumulation calculators. Enter vial size, reconstitution volume, and target dose to get exact draw volumes instantly. No guesswork, just clear guidance that helps prevent common mistakes.
