← All peptidesLongevityOnce-daily subcutaneous protocol for senolytic peptide research.
FOXO4-DRI (also known as Proxofim) is a synthetic D-retro-inverso peptide designed to selectively induce apoptosis in senescent cells by disrupting the FOXO4-p53 protein interaction. When this interaction is blocked, p53 translocates to the mitochondria in senescent cells, triggering their programmed death while sparing healthy cells. This educational protocol presents a once-daily subcutaneous approach using a practical dilution for precise insulin-syringe measurements.
Get FOXO4-DRI → code PROFITProtocol Overview
Concise summary of the regimen.
GoalSelectively clear senescent cells via disruption of FOXO4-p53 binding.
ScheduleDaily subcutaneous injections for 8 to 16 weeks with gradual dose escalation.
Dose Range250 to 500 mcg daily; starting low and titrating upward over time.
Reconstitution3.0 mL per 10 mg vial (~3.33 mg/mL).
StorageLyophilized frozen; reconstituted refrigerated; avoid repeated freeze-thaw.
Dosing & Reconstitution
| WEEK | DAILY DOSE | UNITS PER INJECTION |
|---|
| Weeks 1 to 4 | 250 mcg | 7.5 units (0.075 mL) |
| Weeks 5 to 8 | 375 mcg | 11 units (0.11 mL) |
| Weeks 9 to 12 | 500 mcg | 15 units (0.15 mL) |
| Weeks 13 to 16 | 500 mcg | 15 units (0.15 mL) |
Frequency: Inject once daily subcutaneously. For 10 unit (0.10 mL) or smaller administrations, consider 30- or
Reconstitution Steps
- Draw 3.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl until dissolved (do not shake).
- Label and refrigerate at 2 to 8 °C, protected from light. At 3.33 mg/mL, 1 unit = 0.01 mL » 33.3 mcg on a U-100 insulin syringe.
Storage Instructions
Proper storage preserves peptide quality.
- Lyophilized: store at -20 °C or below in dry, dark conditions; minimize moisture exposure.
- Reconstituted: refrigerate at 2 to 8 °C; use within 1 month when using bacteriostatic water.
- Allow vials to reach room temperature before opening to reduce condensation uptake.
- If long-term storage of reconstituted solution is needed, aliquot into single-use vials and freeze to
minimize degradation.
Supplies Needed
Plan based on an 8 to 16 week daily protocol with gradual titration.
Peptide Vials (FOXO4-DRI, 10 mg each):
- 8 weeks: ~3 vials. 12 weeks: ~4 vials. 16 weeks: ~5 vials.
Insulin Syringes (U-100):
- Per week: 7 syringes (1/day).
- 8 weeks: 56. 12 weeks: 84. 16 weeks: 112.
Bacteriostatic Water (10 mL bottles):
- 8 weeks (3 vials): 1 bottle. 12 weeks (4 vials): 2 bottles. 16 weeks (5 vials): 2 bottles.
Alcohol Swabs:
- Per week: 14 swabs.
- 8 weeks: 112 (2 x 100-count). 16 weeks: 224 (3 x 100-count).
Important Notes
Practical considerations for consistency and safety.
- Use new sterile insulin syringes (typically 29 to 31 gauge, 0.5 inch needle) for each injection; dispose in a
sharps container.
- Rotate injection sites (abdomen, thighs, upper arms) at least 1 inch apart to reduce local irritation.
- Clean the injection site with an alcohol swab and allow to dry before injecting.
- Inject slowly and steadily; no need to aspirate for subcutaneous injections.
- Document daily dose and site rotation to maintain consistency throughout the protocol.
How This Works
FOXO4-DRI is a synthetic peptide that selectively targets senescent cells by blocking the FOXO4-p53 protein interaction. In normal cells, FOXO4 binds to p53 and sequesters it in the nucleus. In senescent cells, disrupting this interaction causes p53 to translocate to the mitochondria, triggering apoptotic cell death specifically in aged, dysfunctional cells while sparing healthy ones. Animal studies have demonstrated that FOXO4-DRI can reduce senescent cell burden, improve tissue function, and mitigate age-related pathologies. The peptide's D-retro-inverso configuration enhances its stability and resistance to proteolytic degradation.
Benefits & Side Effects
Observations from preclinical literature.
- Promotes selective clearance of senescent cells in various tissues, including aged organs and
pathological conditions.
- Animal studies show improvements in tissue regeneration, reduced inflammation, and enhanced organ
function following senescent cell clearance.
- In aged mice, FOXO4-DRI treatment improved testosterone levels and markers of cellular health.
- No human clinical safety or efficacy data currently exist; tolerability in humans remains uncharacterized.
- Injection-site reactions (mild redness, irritation) may occur with subcutaneous administration.
Lifestyle Factors
Complementary strategies for best outcomes.
- Maintain a balanced, nutrient-dense diet rich in antioxidants and anti-inflammatory compounds.
- Combine regular resistance training and cardiovascular activity to support cellular health and metabolic
function.
- Prioritize sleep quality and stress management, both of which influence cellular senescence pathways.
- Stay well-hydrated and avoid excessive alcohol consumption or smoking, which can accelerate cellular
aging.
Injection Technique
General subcutaneous guidance from clinical best-practice resources.
- Clean the vial stopper and skin with alcohol; allow to dry.
- Pinch a skinfold; insert the needle at 45 to 90 degrees into subcutaneous tissue.
- Do not aspirate for subcutaneous injections; inject slowly and steadily.
- Wait 5 to 10 seconds before withdrawing; dispose of syringe in sharps container.
- Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy.
References
Source citations for further reading.
- Baar MP et al. Targeted apoptosis of senescent cells restores tissue homeostasis (Nature Cell): original FOXO4-DRI discovery.
- FOXO4-DRI induces keloid senescent fibroblast apoptosis (Nature Communications Biology).
- FOXO4-DRI alleviates age-related testosterone secretion insufficiency (Aging, Albany NY).
- FOXO4 peptide ameliorates bleomycin-induced pulmonary fibrosis in mice (J Cellular and Molecular Medicine).
Educational and research reference only. Not medical advice. For research use only; not for human consumption.