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Longevity & Anti-AgingNot approved (US)

FOXO4-DRI

Senolytic Peptide FOXO4

Competitive interference with FOXO4–p53 binding restores exclusion of p53 from the nucleus and its mitochondrial apoptosis activity. This preferentially affects senescent cells, whose nuclei contain elevated FOXO4.

Not medical advice. Educational reference only.

Typical dose
Mouse studies: 5 mg/kg by injection 3x weekly; no established human dose
Route
Injectable
Storage
Keep refrigerated at 2–8 °C and use within 28 days.

What is FOXO4-DRI?

FOXO4-DRI is a retro-inverso peptide built from D-amino acids. It targets the association between the FOXO4 transcription factor and p53 that helps senescent cells remain alive. Mouse research published in 2017 found selective death of senescent cells together with better fitness, denser coats and better kidney function. Controlled human trials have not been published. Handle this experimental compound with caution.

Mechanism of action

Competitive interference with FOXO4–p53 binding restores exclusion of p53 from the nucleus and its mitochondrial apoptosis activity. This preferentially affects senescent cells, whose nuclei contain elevated FOXO4.

Targets: FOXO4–p53 interaction · p53 nuclear localization

Research indications

  • Cellular Longevity

    Moderate

    Investigations examine telomere length and the development of cellular senescence.

  • Hormonal Balance

    Moderate

    Potential effects include support for hormonal changes associated with aging.

  • Cognitive Aging

    Limited

    Early investigations examine preservation of cognition as aging progresses.

Interactions

  • Other medications

    Caution

    Consult your prescriber before combining with any medication.

  • BPC-157

    Compatible

  • NAD+

    Compatible

  • Vitamin D

    Compatible

How to reconstitute and inject

Diluent: Use bacteriostatic water only. Avoid saline because it can cause precipitation.

  1. Take the FOXO4-DRI vial out of refrigeration and wait 15–20 minutes for it to reach room temperature.
  2. Disinfect the rubber stopper with an alcohol swab, then let it dry fully in the air.
  3. Use a sterile syringe to measure the calculated amount of bacteriostatic water. Use BAC water only; avoid saline because precipitation can occur.
  4. Direct the water slowly onto the inner vial wall rather than onto the powder.
  5. Rotate the vial gently to mix. Never shake it vigorously; this can degrade the peptide.
  6. Wait 2–3 minutes for complete dissolution, and check that the liquid is transparent and colorless.
  7. Measure your calculated dose into an insulin syringe for a subcutaneous injection.
  8. Choose the abdomen, thigh or upper arm for injection. Change the site each time to help prevent lipodystrophy.
  9. Refrigerate the mixed vial at 2–8 °C and use it within 28 days.

What to expect

Week 1–2
Early effects may emerge during adaptation. Watch for adverse reactions.
Week 2–4
The main effects may start to appear. Change dosing only as your provider recommends.
Week 4–8
The principal effects are expected to be apparent by this stage. Review progress with your provider.
Week 8+
Review the outcome with your provider and decide whether to continue, cycle treatment or adjust the dose.

Side effects and safety

  • Redness, bruising or slight pain at an injection site
  • Possible allergic reactions; stop use if hives or a rash develop
  • Responses differ between individuals; begin with the lowest dose and observe your response carefully
  • Speak with your healthcare provider before use and report unexpected symptoms

FOXO4-DRI: not approved in the US.

Regulatory status

  • US

    Not approved

    FDA — no approval; research use only. No 503A ban is recorded; affirmative compounding authorization remains unestablished.

    Rx required
    No
    Telehealth
    N/A

Frequently asked questions

What is FOXO4-DRI?

FOXO4-DRI is a retro-inverso peptide built from D-amino acids. It targets the association between the FOXO4 transcription factor and p53 that helps senescent cells remain alive. Mouse research published in 2017 found selective death of senescent cells together with better fitness, denser coats and better kidney function. Controlled human trials have not been published. Handle this experimental compound with caution.

How are research schedules specified?

Starting schedules use a low dose, while standard schedules use titration. Frequency follows the individual protocol and the route varies. Neither schedule specifies a numeric dose, so there is no defined amount to calculate from these rows.

What additional dosing or pharmacokinetic information is available?

Mouse experiments use 5 mg/kg by injection 3x weekly. A human dose has not been established. The half-life is unknown; D-amino acids resist proteolysis, extending activity without establishing a numerical duration.

What safety considerations matter?

Adverse effects depend on the amount used, the route and individual response. Human adverse-effect profiles remain incompletely characterized. Consult your healthcare provider before combining compounds, and report unexpected symptoms. The timelines and compatibility categories do not establish clinical effectiveness or prove that combinations are safe.

References

  1. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging (FOXO4-DRI) (2017)

  2. Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression. (2023)

    PMID 36515093DOI 10.1161/CIRCULATIONAHA.122.058794

  3. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. (2017)

    PMID 28340339DOI 10.1016/j.cell.2017.02.031