FOXO4-DRI
FOXO4-DRI is a synthetic senolytic peptide that selectively eliminates senescent cells (cell death/apoptosis) by disrupting the FOXO4/p53 interaction. It is critical for research into longevity and age-associated disorders.
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FOXO4-DRI is a synthetic senolytic peptide designed to selectively induce apoptosis in senescent cells while sparing healthy cells. By disrupting the interaction between FOXO4 and p53, FOXO4-DRI allows the natural cell death pathway to proceed in damaged or senescent cells. This mechanism opens new doors in research related to age-associated disorders, tissue regeneration, and cellular longevity.
– Form: Lyophilized peptide
– Purity: >99%
– Origin: Manufactured and tested in the USA
– Documentation: Certificate of Analysis (COA) included
FOXO4-DRI works by blocking the FOXO4-p53 interaction in senescent cells. In normal cells, FOXO4 binds to p53 and prevents it from initiating apoptosis. In senescent cells, this leads to accumulation and inflammation. FOXO4-DRI disrupts this interaction, freeing p53 to trigger cell death and selectively clearing dysfunctional cells, reducing inflammatory burden and potentially improving tissue function.
– Senescence and aging research
– Studies on tissue regeneration and repair
– Inflammation and immune aging models
– Neurodegeneration and frailty studies
– Oncology and preclinical senolytic trials
– Promotes clearance of senescent cells
– Reduces chronic inflammation and SASP (senescence-associated secretory phenotype)
– Improves tissue health and regenerative potential
– Aids in studying anti-aging mechanisms at the cellular level
Each vial is:
– Produced in a GMP-compliant U.S. facility
– Accompanied by a Certificate of Analysis (COA)
– Verified via HPLC and mass spectrometry
– Securely shipped with quality-control documentation
– Contents: 5mg FOXO4-DRI lyophilized peptide
– Appearance: White to off-white powder
– Solubility: Reconstitute with sterile bacteriostatic water
– Storage: Store at -20°C; refrigerate after reconstitution and use within 30 days
*For research use only. Not for human or veterinary consumption.*
– Intended for laboratory research only
– Not approved for human consumption or clinical use
– Buyer assumes all responsibility for legal research use
It selectively removes senescent cells, a key contributor to aging and chronic inflammation, allowing healthier cell turnover.
Yes, studies show that FOXO4-DRI specifically targets senescent cells by disrupting their unique FOXO4-p53 pathway.
All vials are tested for >99% purity via HPLC and mass spectrometry, with a COA included for every batch.
It remains stable for up to 30 days under refrigeration.
FOXO4-DRI (10 mg Vial) Dosage Protocol
Quickstart Highlights
FOXO4-DRI dosage protocols focus on this innovative senolytic peptide (also known as Proxofim) designed to selectively target and eliminate senescent "zombie" cells. As a D-retro-inverso analog of the FOXO4 protein segment, FOXO4-DRI works by disrupting the FOXO4-p53 interaction in senescent cells, freeing p53 to trigger apoptosis and clear dysfunctional cells[1][2]. Preclinical research has demonstrated benefits including improved physical fitness, restored organ function, enhanced hormonal balance, and reduced tissue fibrosis in aged animal models[3][4]. This educational protocol presents an intermittent subcutaneous approach using a practical dilution for accurate insulin-syringe measurements.
- Reconstitute: Add 3.0 mL bacteriostatic water → 3.33 mg/mL concentration.
- Typical dose range: 300–500 mcg once daily during dosing weeks.
- Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL ≈ 33.3 mcg on a U-100 insulin syringe.
- Storage: Lyophilized: freeze at −20 °C (−4 °F); after reconstitution, refrigerate at 2–8 °C (36–46 °F); avoid freeze–thaw cycles.
Dosing & Reconstitution Guide
Educational guide for reconstitution and intermittent pulse dosing
Standard / Intermittent Pulse Approach (3 mL = 3.33 mg/mL)
| Week/Phase | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Week 1 (Days 1–7) | 300 mcg | 9 units (0.09 mL) |
| Week 2 (Days 8–14) | Off | No injection |
| Week 3 (Days 15–21) | 400 mcg | 12 units (0.12 mL) |
| Week 4 (Days 22–28) | Off | No injection |
Frequency: Inject once daily subcutaneously during dosing weeks. Senolytics like FOXO4-DRI are most effective with intermittent "hit-and-run" dosing rather than continuous administration[2][5]. For ≤10-unit (≤0.10 mL) administrations, consider 30- or 50-unit insulin syringes for improved readability.
Reconstitution Steps
- Draw 3.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming or harsh agitation.
- Gently swirl/roll until dissolved (do not shake).
- Label with date and refrigerate at 2–8 °C (36–46 °F), protected from light.
Supplies Needed
Plan based on a 2–4 week intermittent protocol (1 week on, 1 week off cycles).
- Peptide Vials (FOXO4-DRI, 10 mg each):
- 1 cycle (7 doses at 400 mcg) ≈ 2.8 mg → 1 vial
- 2 cycles (14 doses at 400 mcg) ≈ 5.6 mg → 1 vial
- 3 cycles (21 doses at 500 mcg) ≈ 10.5 mg → 2 vials
- Insulin Syringes (U-100):
- Per dosing week: 7 syringes (1/day)
- 1 cycle (2 weeks): 7 syringes
- 2 cycles (4 weeks): 14 syringes
- 3 cycles (6 weeks): 21 syringes
- Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- 1–2 cycles (1 vial): 3 mL → 1 × 10 mL bottle
- 3 cycles (2 vials): 6 mL → 1 × 10 mL bottle
- Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- Per dosing week: 14 swabs (2/day)
- 1 cycle: 14 swabs
- 2 cycles: 28 swabs
- 3 cycles: 42 swabs → recommend 1 × 100-count box
Protocol Overview
Concise summary of the intermittent senolytic regimen.
- Goal: Selectively eliminate senescent cells to support tissue rejuvenation and restore healthy cellular function[1][3].
- Schedule: 1 week on, 1 week off cycles; 1–3 cycles total (2–6 weeks).
- Dose Range: 300–500 mcg daily during dosing weeks.
- Reconstitution: 3.0 mL per 10 mg vial (3.33 mg/mL) for accurate unit measurements.
- Storage: Lyophilized frozen; reconstituted refrigerated; avoid repeated freeze–thaw.
Dosing Protocol
Suggested intermittent pulse dosing approach.
- Start: 300 mcg daily during first dosing week.
- Target: 400–500 mcg daily for subsequent cycles if well-tolerated.
- Frequency: Once per day (subcutaneous) during dosing weeks only.
- Cycle Structure: 7 days on → 7 days off; repeat 1–3 times.
- Timing: Any consistent time; rotate injection sites.
Storage Instructions
Proper storage preserves peptide quality and integrity.
- Lyophilized: Store at −20 °C (−4 °F) or below; −80 °C ideal for long-term storage[6].
- Reconstituted: Refrigerate at 2–8 °C (36–46 °F); use within 28 days with bacteriostatic water[7].
- Allow vials to reach room temperature before opening to reduce condensation uptake.
- Protect from light; keep stopper secure to prevent moisture exposure.
Important Notes
Practical considerations for consistency and safety.
- Use new sterile insulin syringes for each injection; dispose in a sharps container.
- Rotate injection sites (abdomen, thighs, upper arms) to prevent local irritation.
- Inject slowly; wait a few seconds before withdrawing the needle.
- Document daily dose, site rotation, and any observations to maintain consistency.
- Discard reconstituted solution after 28 days regardless of remaining volume[7].
How This Works
FOXO4-DRI is a cell-penetrating peptide antagonist that targets the FOXO4-p53 interaction in senescent cells[1]. In senescent cells, FOXO4 abnormally accumulates in the nucleus and binds to p53, preventing apoptosis[2]. FOXO4-DRI is engineered with D-amino acids (D-retro-inverso configuration) to resist degradation while mimicking the FOXO4 binding region[8]. By displacing native FOXO4 from p53, the peptide frees p53 to relocalize to mitochondria and initiate apoptosis specifically in senescent cells, while sparing healthy cells that lack the high nuclear FOXO4-p53 complexes[1][9]. This selective senolytic action can reduce chronic inflammation from SASP (senescence-associated secretory phenotype) factors and restore tissue homeostasis[3].
Potential Benefits & Side Effects
Observations from preclinical animal and cell culture studies.
- Supports selective clearance of senescent cells while sparing healthy, proliferating cells[9][10].
- Preclinical studies showed improved physical fitness, fur density, and organ function in aged mice[3].
- Research demonstrated restored testosterone levels in aged male mice by clearing senescent Leydig cells[4].
- Reduced fibrotic tissue damage in pulmonary fibrosis models[11].
- Animal studies reported no overt adverse effects; body and organ weights remained unchanged[4].
- Mild injection-site reactions (redness) may occur with subcutaneous administration.
- Note: No human clinical trials have been completed as of 2025; all data are preclinical[2].
Lifestyle Factors
Complementary strategies for optimal outcomes.
- Maintain a balanced, nutrient-dense diet to support cellular health and recovery.
- Engage in regular physical activity to reinforce metabolic and functional adaptations.
- Prioritize quality sleep and stress management to support tissue repair processes.
- Allow adequate rest during off-weeks for senescent cell clearance and tissue remodeling.
Injection Technique
General subcutaneous guidance from clinical best-practice resources[12].
- Clean the vial stopper and skin with alcohol; allow to dry completely.
- Pinch a skinfold; insert the needle at 45–90° into subcutaneous tissue[12].
- Do not aspirate for subcutaneous injections; inject slowly and steadily.
- Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy.
- Keep subsequent injections at least 1 inch apart from previous sites in the same region.
Recommended Source
We recommend Shop Peptides Direct for high-purity FOXO4-DRI (10 mg).
Why Shop Peptides Direct?
- High-purity (≥98%), third-party-tested lots with batch COAs.
- Consistent, ISO-aligned handling and documentation.
- Reliable fulfillment to maintain cold-chain integrity.
Important Note
This content is intended for therapeutic educational purposes only and does not constitute medical advice, diagnosis, or treatment.
References
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Nature Communications (2025) — The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI
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Aging (Albany NY) (2020) — FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
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Cell (2017) — Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
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Aging (Albany NY) (2020) — FOXO4-DRI clears senescent Leydig cells, restoring testosterone in aged mice without adverse effects
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ScienceDirect — Senotherapy for chronic lung disease: intermittent senolytic dosing strategies
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JPT Peptide Technologies — How to Store Peptides: Best Practices for Researchers
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CDC — Preventing Unsafe Injection Practices: Multi-dose vial 28-day rule
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Sigma-Aldrich (Merck) — Peptide Handling Guide: Storage and stability of synthetic peptides
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Frontiers in Bioengineering and Biotechnology (2021) — Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes
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Bachem — Handling and Storage Guidelines for Peptides
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PubMed / J Cell Mol Med (2022) — FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice
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MedlinePlus (U.S. NLM) — Subcutaneous (SQ) injections: Patient Instructions
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