FOXO4-DRI
Also called FOXO4 D-retro-inverso peptide; Proxofim
An experimental "senolytic" peptide designed to trigger the removal of certain aging (senescent) cells. The key evidence comes from cell and mouse studies, not human trials.
Overview
What it is
A designed peptide that blocks the interaction between the FOXO4 protein and p53. "DRI" refers to its mirror-image amino-acid design, which makes it more resistant to breakdown.
How it works
Senescent cells have stopped dividing but stay metabolically active. Blocking FOXO4-p53 releases p53 and pushes these cells toward programmed cell death (apoptosis). Whether this stays selective across tissues in a whole body is not settled.
What the research shows
A 2017 Cell study reported better fitness, fur density and kidney function in aging mice. Later mouse studies (2020, 2024) reported improvements in testicular environment, testosterone-related findings and sperm measures. A 2026 study looked at blood-vessel cells and aortic function in aging mice. None were human treatment trials.
Studied for
- Senescent cell clearancecell and mouse
- Testicular aging and sperm measuresmice
- Vascular agingmice
Safety and regulatory status
Safety and side effects
There is no dependable human side-effect rate or interaction profile. A compound meant to cause cell death needs careful study of which cells it affects. Senescence also plays useful roles, such as in wound healing, so more clearance is not automatically better.
Regulatory status
Not approved by the FDA for any use.
Mixing and dosing reference
Reference information only. Read before using this section.
FOXO4-DRI (10 mg Vial) Dosage Protocol
- Vial
- 10 mg FOXO4-DRI
- Add diluent
- 3 mL
- Concentration
- 3.33 mg/mL
- 1 unit (U-100)
- 33.33 mcg in 0.01 mL
- Route
- Subcutaneous
- How often
- Once per day (subcutaneous).
- Typical range
- 250–500 mcg once daily (gradual titration over 16 weeks).
- Cycle length
- 8–16 weeks; longer cycles may use intermittent dosing schedules as tolerated.
Standard / Gradual Approach
| Week | Daily Dose (mcg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–4 | 250 mcg | 7.5 units (0.075 mL) |
| Weeks 5–8 | 375 mcg | 11 units (0.11 mL) |
| Weeks 9–12 | 500 mcg | 15 units (0.15 mL) |
| Weeks 13–16 | 500 mcg | 15 units (0.15 mL) |
How to mix
- Draw 3.0 mL bacteriostatic water with a sterile syringe.
- Inject slowly down the vial wall; avoid foaming.
- Gently swirl/roll until dissolved (do not shake).
- Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
Dosing details
- Start: 250 mcg daily for the first 4 weeks; increase gradually as tolerated.
- Mid-Phase: 375 mcg daily during Weeks 5–8.
- Target: 500 mcg daily by Weeks 9–16.
- Frequency: Once per day (subcutaneous).
- Cycle Length: 8–16 weeks; longer cycles may use intermittent dosing schedules as tolerated.
- Timing: Any consistent time; rotate injection sites to minimize local irritation.
Storage
- Lyophilized: Store at −20 °C (−4 °F) or below in dry, dark conditions; minimize moisture exposure.
- Reconstituted: Refrigerate at 2–8 °C (35.6–46.4 °F); follow formulation-specific use-by and sterile-handling instructions; bacteriostatic water alone does not establish shelf life.
- Allow vials to reach room temperature before opening to reduce condensation uptake.
- Do not assume aliquoting or freezing a reconstituted solution extends stability or sterility without validated evidence.
Administration technique
- Clean the vial stopper and skin with alcohol; allow to dry.
- Pinch a skinfold; insert the needle at 45–90° into subcutaneous tissue (use 90° for adequate fat layer, 45° if thin).
- Do not aspirate for subcutaneous injections; inject slowly and steadily.
- Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy and local irritation.
- Release the pinch and withdraw the needle; apply gentle pressure with gauze if slight bleeding occurs.
Important notes
- Use new sterile insulin syringes (typically 29–31 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.
Protocol source: PeptideDosages.com
Common questions
Does FOXO4-DRI extend lifespan?
Improvements in aging mice do not prove longer human lifespan.
Is it the same as other senolytics?
No. "Senolytic" is a research approach, not one interchangeable drug class.
Can it raise testosterone or sperm count?
The findings are from cell models and aged mice and do not establish a benefit in men.
Related in Healthy Aging
Sources and further reading (5)
- Baar MP, et al. Targeted senescent-cell apoptosis in chemotoxicity and aging models. Cell, 2017.
- FOXO4-DRI, senescent Leydig cells and testosterone in aged mice. Aging, 2020.
- FOXO4-DRI and spermatogenesis in aged mice, 2024.
- Hu Z, et al. FOXO4-DRI and endothelial-cell senescence through p53 signaling. Front Bioeng Biotechnol, 2026.
- Source summary: PeptideDosages.com research overview (rewritten for NVO).