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For research and educational purposes only. Not intended for human consumption.

FOXO4-DRI

Limited Research
Updated Dec 2025

Senolytic Peptide | FOXO4-p53 Disruption for Cellular Aging Research

Injectable
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~25mg per injection
Every other day × 3
Injectable
SubQ: Abdominal fat (anecdotal human protocols)
5 days per cycle
Typical duration
-20°C
Storage

Overview

What is FOXO4-DRI?

FOXO4-DRI (FOXO4-D-Retro-Inverso) is a synthetic 46-amino acid peptide designed to selectively eliminate senescent cells - damaged cells that accumulate with age and secrete harmful inflammatory factors (SASP). The peptide uses D-amino acids in reversed sequence, making it resistant to proteolytic degradation while maintaining binding function. It shows 11.73-fold selectivity for senescent over healthy cells.

Key Benefits

Selective senescent cell elimination, tissue homeostasis restoration, potential anti-aging effects. Mouse studies showed restored fur density, renal function, and physical fitness.

Mechanism of Action

Disrupts FOXO4-p53 interaction in senescent cells, causing p53 nuclear exclusion. Free p53 translocates to mitochondria, triggering caspase-dependent apoptosis specifically in senescent cells while sparing healthy cells (11.73-fold selectivity demonstrated).

Molecular Information

5,358.2 Da
Weight
46
amino acids
D-Retro-Inverso peptide with cell-penetrating domain
Type
Amino Acid Sequence:
H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH (all D-amino acids)
* D-Retro-Inverso: Reversed sequence with D-amino acids. Preserves side-chain topology for receptor binding while providing protease resistance. Contains C-terminal HIV-TAT-derived cell-penetrating peptide.

Pharmacokinetics

Peak
4 hrs
Half-life
1-3 days
Cleared
5-15 days
100%50%0%0h6h12h18h24h
Peak
Half-life
Cleared
Baar et al. 2017 Cell

Research Indications

Senescent Cell Clearance

Selectively eliminates 'zombie' senescent cells that accumulate with age and secrete harmful inflammatory factors (SASP).

Tissue Homeostasis

Mouse studies show restoration of tissue function including fur regrowth, renal function, and physical fitness.

Rejuvenation

Potential to restore youthful tissue function by removing accumulated senescent cells.

Research Protocols

Disclaimer: CRITICAL: FOXO4-DRI is a research compound with NO human clinical data. Dosing protocols are translated from mouse studies or derived from anecdotal self-experimentation. Human pharmacokinetics, optimal dosing, and long-term safety are completely unknown. This peptide targets the p53 tumor suppressor pathway - proceed only with full understanding of experimental nature.

GoalDoseFrequencyRoute
Mouse Research Protocol (IV)5 mg/kgEvery other day × 3 dosesIV
Mouse Research Protocol (IP)5 mg/kgEvery other day × 3 dosesIP
Anecdotal Human Translation~25 mg per injectionEvery other day × 3 doses (75-100 mg total per cycle)SubQ

Timing: Cellular uptake within 2-4 hours, detectable for 72+ hours. D-amino acid structure provides protease resistance.

Peptide Interactions

How to Reconstitute

Important: Always use bacteriostatic water (BAC). Sterile technique is essential.

1

Store lyophilized powder at -20°C until use

2

Allow vial to reach room temperature before reconstitution

3

Add sterile water slowly down vial side

4

Gently swirl until dissolved - do not shake (protein may denature)

5

Solution should be clear; discard if cloudy or precipitated

6

Use reconstituted solution within 7-10 days

7

Store reconstituted at 2-8°C

Dosing Calculator

Calculate your injection volume with visual dosing guide

FINAL CONCENTRATION
2.50mg/mL
Each milliliter contains 2.50 mg of peptide
VISUAL REFERENCE (RESEARCH USE ONLY)

To obtain 250 mcg from this solution:

Draw 0.10 mL=10 units

(1 mL = 100 units on any insulin syringe)

0102030405060708090100
00.10.20.30.40.50.60.70.80.91.0
0.10 mL
10 units

Draw to this mark for 250 mcg

This calculator is for research purposes only. Always verify calculations and consult protocols.

Quality Indicators

No Human Clinical Trials

All data from mouse studies and cell culture. Human pharmacokinetics, safety, and efficacy unknown.

p53 Pathway Involvement

p53 is a critical tumor suppressor. Long-term effects of repeated FOXO4-p53 modulation unknown.

High Synthesis Cost

46 D-amino acids make production expensive. Risk of low-quality or counterfeit products.

High Selectivity Demonstrated

11.73-fold selectivity for senescent vs healthy cells in original research.

Third-Party Testing Essential

Due to complex D-amino acid synthesis, verify peptide identity and purity via independent testing.

Avoid with Rapamycin/Quercetin

May diminish senolytic effects. Require 1-2 week washout period.

What to Expect

  • Week 1: No reliable human timeline established
  • Mouse studies: Improvements seen within 1-4 weeks
  • Fur density restored in aged mice within 2-3 weeks
  • Renal function normalized within study period (weeks)
  • Human effects poorly characterized; proceed with caution

Side Effects & Safety

Side Effects

  • CRITICAL: No human clinical trials - all safety data from animal studies
  • Original mouse studies showed no thrombocytopenia (unlike ABT-737)
  • No cardiac abnormalities on histology in mouse studies
  • Does not sensitize healthy cells to DNA damage
  • Anecdotal: Burning/itching at injection site reported
  • Avoid concurrent use with Rapamycin, Quercetin, corticosteroids
  • May not be useful for healthy individuals under 40 with low senescent cell burden
  • Theoretical concern: p53 pathway critical for tumor suppression
  • Unknown immunogenicity with repeated dosing

When to Stop

  • Signs of unexpected immune reaction
  • Severe injection site reactions
  • Any signs of abnormal cell growth
  • Persistent fatigue or weakness
  • Consult healthcare provider immediately

References

3 Studies

Targeted Apoptosis of Senescent Cells (2017)

Mouse | 5 mg/kg IV | 3 doses every other day | 11.73-fold selectivity for senescent cells

Landmark study introducing FOXO4-DRI. In aged mice, restored fur density, normalized renal function, increased voluntary running activity, and protected against doxorubicin-induced liver damage.

View Study

Age-Related Testosterone Insufficiency (2020)

Mouse | 5 mg/kg IP | Every other day × 3 | Increased serum testosterone

Treatment significantly increased serum testosterone levels in aged mice. Enhanced expression of testosterone synthesis enzymes. Decreased testicular senescence markers.

Senolytic Effect on Human Chondrocytes (2021)

Human cells in vitro | Passaged chondrocytes | Removed over 50% senescent cells

Removed over 50% of highly-passaged senescent chondrocytes while not affecting minimally-passaged cells. Reduced senescence markers and improved cartilage quality.

Quick Start Guide

Typical Dose
No established human dose. Mouse: 5 mg/kg. Anecdotal human: ~25 mg
How Often
Every other day × 3 doses per cycle
Where to Inject
SubQ: Abdominal fat (anecdotal human protocols)
Timing
No established optimal timing. Cellular uptake occurs within 2-4 hours, effects persist 72+ hours
Effects Timeline
Mouse studies showed improvements in 1-4 weeks. Human timelines unknown.
Storage
Lyophilized: -20°C. Reconstituted: 2-8°C, use within 7-10 days
Cycle Length
5 days per cycle (3 injections on days 1, 3, 5)
Break Between
Anecdotal protocols suggest monthly cycles

Research Disclaimer

FOXO4-DRI is sold for laboratory research purposes only and is not intended for human or animal consumption. The information provided on this page is compiled from published research, veterinary studies, and anecdotal reports for educational purposes. This content does not constitute medical advice, diagnosis, or treatment recommendations. Any research involving FOXO4-DRI must comply with all applicable local, state, and federal regulations. BioInfinity Lab makes no claims regarding the safety or efficacy of FOXO4-DRI for any purpose. Consult qualified professionals for any research applications.