Peptides

FOXO4-DRI

Evidence: animal_plus_anecdotal

Mechanism of Action

FOXO4-DRI is a D-retro-inverso peptide that selectively targets the FOXO4-p53 protein-protein interaction in senescent cells. In senescence, FOXO4 binds p53's disordered transactivation domain (TAD2) in the nucleus, preventing p53 from translocating to mitochondria where it would trigger apoptosis. FOXO4-DRI competitively disrupts this interaction, causing nuclear exclusion of p53 and its redirection to mitochondria, selectively inducing apoptosis in senescent cells while sparing healthy cells. The D-retro-inverso configuration provides protease resistance.

Dosing Protocol

Standard: Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly.

Administration: intravenoussubcutaneous

Timing: No established timing protocol.

Duration: Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established.

Notes

FOXO4-DRI is the most targeted senolytic peptide identified to date. The landmark 2017 Cell paper by Baar et al. demonstrated that FOXO4-DRI restored fur density, renal function, and fitness in naturally aged mice. In 2025, Nature Communications published structural insights into the FOXO4-p53 interaction, advancing therapeutic development. This is a frontier longevity compound — exciting science but no human trials. The D-retro-inverso configuration makes it expensive to synthesize. Cost and availability are significant barriers. For practical senolytic interventions, the Dasatinib + Quercetin stack has more human data.

Stacking

  • Epitalon
  • GHK-Cu
  • Dasatinib + Quercetin (D+Q senolytic stack)

Interactions

  • Chemotherapy [HIGH] — FOXO4-DRI may kill chemotherapy-induced senescent cells, potentially altering treatment dynamics.
  • Other senolytics (Dasatinib, Quercetin, Fisetin) [MEDIUM] — Additive senolytic effects; monitor for excessive cell death and immune activation.
  • Immunosuppressants [MEDIUM] — Senescent cell clearance triggers immune responses; immunosuppression may alter this process.

Contraindications

  • Active cancer (complex interaction with p53 pathway)
  • Pregnancy and breastfeeding
  • Severe organ failure
  • Immunocompromised state

Side Effects

  • Theoretical: senolytic crisis (rapid senescent cell clearance causing inflammation)
  • Unknown long-term effects in humans
  • Potential cytokine release

Key Papers

  • 10.1016/j.cell.2017.02.031
  • 10.18632/aging.102682

Source Quality

Research-grade supplier only. D-retro-inverso peptide synthesis is complex; verify configuration on COA. Extremely limited availability.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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