← Peptide Database/FOXO4-DRI
LongevityTier 4 β€” Preclinical only

FOXO4-DRI

FOXO4-p53 disruptor Β· Senolytic peptide

A retro-inverso peptide that selectively induces apoptosis in senescent cells by disrupting the FOXO4–p53 interaction. Demonstrated clearance of senescent cells and reversal of age-related frailty, hair loss, and renal dysfunction in mouse models.

πŸ’‰ IP injection (animal research); SC/IV experimental in humans🧊 Lyophilised: βˆ’20 Β°C long-term. Reconstituted: use immediately or store at βˆ’80 Β°C. Sensitive to freeze-thaw cycles.

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Mechanism of Action

Senescent cells overexpress FOXO4, which retains p53 in the nucleus and prevents apoptosis. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, releasing p53 to trigger mitochondrial apoptosis exclusively in senescent cells while sparing healthy cells.

Clinical Applications

  • βœ“Senolytic therapy β€” clearance of senescent cells
  • βœ“Frailty and age-related functional decline (preclinical)
  • βœ“Alopecia associated with cellular senescence (preclinical)
  • βœ“Chronic kidney disease linked to senescent accumulation (preclinical)
  • βœ“Longevity research protocols

Dosing Protocol

Recommended Dosing

No established human dosing. Mouse studies: 5 mg/kg IP injection 3Γ—/week for 1–3 weeks. Human translational dosing remains entirely experimental. Not for clinical use.

Safety & Contraindications

Possible Side Effects

  • ⚠Unknown safety profile in humans
  • ⚠Potential off-target apoptosis in non-senescent cells (theoretical)
  • ⚠Risk of immune response to non-natural D-amino acid peptide
  • ⚠Injection site reactions possible

Contraindications

  • βœ•All human use outside approved clinical trials
  • βœ•Active cancer (theoretical risk of disrupting tumour suppression)
  • βœ•Immunosuppressed patients
  • βœ•Pregnancy and breastfeeding

Combinations & Synergies

πŸ”— Theoretical stack with other senolytics (dasatinib + quercetin) β€” purely research context
πŸ”— NAD+ precursors (NMN/NR) for complementary senescence-associated pathway support
#senolytic#senescence#FOXO4#p53#apoptosis#longevity#frailty#preclinical#Tier-4
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