FOXO4-DRI

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 FOXO4-DRI (Forkhead Box O4 – D-Retro-Inverso) is a synthetic peptide designed to selectively induce apoptosis (self-destruction) in senescent cells — aging cells that no longer divide but release inflammatory signals known as the senescence-associated secretory phenotype (SASP).

Developed from the FOXO4 transcription factor, FOXO4-DRI is a cell-penetrating senolytic peptide, meaning it helps clear aged or damaged cells, potentially rejuvenating surrounding tissues and restoring youthful cellular function.

FOXO4-DRI targets the interaction between the FOXO4 protein and p53, a key pathway that allows senescent cells to avoid programmed cell death.

When FOXO4-DRI disrupts this binding, p53 is released, triggering apoptosis in senescent cells — while leaving healthy cells largely unaffected.

1. Selective removal of senescent cells – restores tissue homeostasis
    
2. Reduction in inflammatory cytokines (SASP) – lowers chronic inflammation
    
3. Improved mitochondrial function – rejuvenates cellular energy systems
    
4. Enhanced tissue regeneration – promotes recovery and repair capacity
    
5. Potential lifespan extension – through senolytic and anti-aging effects
    

Senolytic activity

Induces apoptosis in senescent cells

Anti-aging research

Restores tissue vitality and organ function

Inflammation control

Reduces SASP and systemic inflammatory markers

Cellular rejuvenation

Improves mitochondrial and stem cell performance

Longevity

Suggested extension of healthspan in animal studies

Injectable (intraperitoneal or subcutaneous, research setting)

5–10 mg/kg

Administered every 2–3 days

Peptide solution (in vitro research)**

10–100 μM concentration range

Dose-dependent cellular assays

• Cycle duration (research): Often studied in short intermittent cycles (e.g., 3–7 days)
   
• Half-life: Short, rapid cell-penetrating activity
   
• Synergistic research: Sometimes evaluated with Dasatinib + Quercetin or Rapamycin analogues for combined senolytic action