FOXO4-DRI
FDA APPROVAL PENDING
Emerging
Longevity
FOXO4-DRI
46
Amino acids
Molecular weight
Peptide
Type
FOXO4-DRI is a senolytic peptide designed to selectively eliminate senescent 'zombie' cells that accumulate with age and contribute to tissue dysfunction. It works by disrupting the FOXO4-p53 interaction that keeps senescent cells alive. The 'DRI' modification (D-retro-inverso) uses reversed D-amino acids to increase potency and stability. Preclinical research shows restoration of fur density, fitness, and organ function in aged mice.
Top researched benefits
Overview of FOXO4-DRI
FOXO4-DRI competes with FOXO4 for binding to p53, disrupting their protective interaction in senescent cells. This causes p53 to be excluded from the nucleus and triggers cell-intrinsic apoptosis (programmed cell death). Critically, this mechanism is highly selective: the FOXO4-p53 interaction is a specific vulnerability of senescent cells, while FOXO4 is minimally expressed in healthy tissues, leaving functional cells largely unharmed.
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
25-33 mg per injection (based on mouse study 5 mg/kg)
Frequency
3 doses total, administered every other day (Day 1, 3, 5)
Cycle Duration
6 days (3 doses total = 75-100 mg per treatment cycle)
Storage
Lyophilized: -20°C frozen; Reconstituted: 2-8°C refrigerated, use immediately or within short term; avoid freeze-thaw cycles
Chemical Makeup
Key benefits
Selective elimination of senescent cells
Restoration of tissue homeostasis
Improved fitness and physical function in aged models
Restored fur density in aged mice
Improved kidney function
Alleviates chemotherapy-induced senescence
Restores testosterone in aged males
Reduces senescent chondrocytes in cartilage
High selectivity spares healthy cells
Community interest
This peptide is still gaining traction in the community.
Senolytic Peptide | p53-FOXO4 Disruptor
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
5358DaChain Length
46Amino AcidsType
PeptideFOXO4-DRI Protocols
Currently in experimental stages. The original 2017 mouse study used 5 mg/kg intraperitoneally, three times on alternate days. For a 60kg human, this translates to approximately 25 mg per dose. Self-experimenters have reported using subcutaneous injection. Storage at -20°C required due to peptide stability concerns.
| Goal | Dosage | Frequency | Route |
|---|---|---|---|
| Standard senolytic protocol | 25 | 3 week range | SubQ or IV |
| Mouse study equivalent | 5 | 3 week range | IP (original study) |
Reconstitution Instructions
Materials needed:
Steps to reconstitute
- Store peptide at -20°C until use
- Reconstitute according to research protocol
- Use immediately or store at 4°C short-term
- Avoid repeated freeze-thaw cycles
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
- 25-33 mg per injection (based on mouse study 5 mg/kg)
- Dosing Frequency
- 3 doses total, administered every other day (Day 1, 3, 5)
- Cycle Duration
- 6 days (3 doses total = 75-100 mg per treatment cycle)
- Storage
- Lyophilized: -20°C frozen; Reconstituted: 2-8°C refrigerated, use immediately or within short term; 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
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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 an emerging compound
FOXO4-DRI
FOXO4-DRI is an emerging 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.