DG Peptide Protocols
EmergingLongevity

FOXO4-DRI

FOXO4-D-Retro-Inverso

Senolytic Peptide | p53-FOXO4 Disruptor

Half-life
Not established
Chain length
~45 amino acids
Reference frequency
3 doses total, administered every other day (Day 1, 3, 5)

Research overview

DoseGear research brief

FOXO4-DRI is a senolytic peptide designed to selectively eliminate senescent 'zombie' cells that accumulate with age and contribute to tissue dysfunction. It works by disrupting the FOXO4-p53 interaction that keeps senescent cells alive. The 'DRI' modification (D-retro-inverso) uses reversed D-amino acids to increase potency and stability. Preclinical research shows restoration of fur density, fitness, and organ function in aged mice.

Mechanism of action

FOXO4-DRI competes with FOXO4 for binding to p53, disrupting their protective interaction in senescent cells. This causes p53 to be excluded from the nucleus and triggers cell-intrinsic apoptosis (programmed cell death). Critically, this mechanism is highly selective: the FOXO4-p53 interaction is a specific vulnerability of senescent cells, while FOXO4 is minimally expressed in healthy tissues, leaving functional cells largely unharmed.

Compound background

Development & research timeline

Study windows describe what researchers measured, not when an individual should expect a result.

Origin & development

D-retro-inverso peptide designed around the FOXO4–p53 interaction.

What it is researched for

Experimental senescent-cell elimination by disrupting FOXO4–p53 binding in susceptible cells.

Research observation window

A cited mouse experiment used three injections on alternate days; this is an exposure schedule, not a human response estimate.

Reference data

Lyophilized vial injectable protocols

Not personalized dosing instructions

Only injectable vial references are shown. Nasal, topical, and unsupported non-vial schedules are excluded.

Research contextAmountFrequencyRoute
Standard senolytic protocol25-33 mg3 doses, every other day (6 days total)SubQ or IV
Mouse study equivalent5 mg/kg (translates to ~25 mg for 60kg human)3 doses on alternate daysIP (original study)

Reference cycle

6 days (3 doses total = 75-100 mg per treatment cycle)

Reference storage

Lyophilized: -20°C frozen; Reconstituted: 2-8°C refrigerated, use immediately or within short term; avoid freeze-thaw cycles

Safety context

Reported side effects

  • Limited human data available
  • Generally well-tolerated in animal studies

Contraindications & cautions

  • Not yet approved for human use
  • Pregnancy or breastfeeding
  • Unknown safety in immunocompromised individuals
  • Active cancer (theoretical - consult oncologist)

Scientific references

  1. 01

    Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis

    Scientific citationTargeted Apoptosis of Senescent Cells Restores Tissue Homeostasis. Cell (2017).
  2. 02

    An Example of Senolytic Self-Experimentation with FOXO4-DRI

    Scientific citationAn Example of Senolytic Self-Experimentation with FOXO4-DRI. Fight Aging! (2017).
  3. 03

    FOXO4-DRI Alleviates Age-Related Testosterone Secretion Insufficiency

    Scientific citationFOXO4-DRI Alleviates Age-Related Testosterone Secretion Insufficiency. Theranostics (2020).
  4. 04

    FOXO4-DRI Removes Senescent Cells from Human Chondrocytes

    Scientific citationFOXO4-DRI Removes Senescent Cells from Human Chondrocytes. Frontiers in Bioengineering and Biotechnology (2021).

This DoseGear profile combines published scientific literature with lyophilized-vial protocol references. Citations are provided for independent review.

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