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FOXO4-DRI

A senolytic peptide that selectively eliminates damaged zombie cells for anti-aging. FOXO4-DRI is a D-retro-inverso peptide that selectively eliminates senescent (zombie) cells by disrupting the FOXO4-p53 interaction. This senolytic mechanism triggers apoptosis specifically in damaged cells while sparing healthy ones. A cutting-edge anti-aging research compound based on the landmark 2017 Cell paper.

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🧬Key Characteristics
  • Design: D-retro-inverso
    (All-D amino acids, reversed sequence.)
  • Target: FOXO4-p53 complex
    (Disrupts senescent cell survival.)
  • Selectivity: Senescent cells only
    (Healthy cells unaffected.)
  • Key Study: Baar et al. 2017 (Cell)
    (Restored fitness in aged mice.)
Peptide design
D-amino acid retro-inverso of FOXO4 p53-binding domain
The D-retro-inverso design makes FOXO4-DRI highly resistant to proteases while maintaining the spatial orientation needed to compete with endogenous FOXO4 for p53 binding in senescent cells.
Key takeaway: FOXO4-DRI is one of the most targeted senolytic approaches, selectively eliminating damaged cells that drive aging. Unlike broad senolytics (dasatinib + quercetin), it specifically disrupts the survival mechanism of senescent cells.

Overview

Core Benefits

Key Advantages
Selective senolytic
Specifically targets senescent 'zombie' cells while sparing healthy cells — precision anti-aging.
FOXO4-p53 disruption
Breaks the protective FOXO4-p53 interaction that keeps damaged cells alive.
SASP reduction
Clearing senescent cells reduces the inflammatory secretory phenotype that accelerates aging.
Tissue rejuvenation
Mouse studies showed restored fitness, kidney function, and fur density after treatment.
Protease-resistant
D-retro-inverso design makes it highly stable against enzymatic breakdown.
Landmark research
Based on the 2017 Cell paper by Baar et al. — one of the most cited senolytic studies.

These are educational summaries of commonly discussed effects in wellness/regenerative contexts, not guarantees.

FOXO4-DRI Results Timeline

Progression
1
Week 1–2
Physical Changes
Senescent cell apoptosis initiated, immune clearance begins
Performance & Recovery
May feel mild fatigue as body clears damaged cells
Other Benefits
Working at the cellular level — no visible changes yet
2
Week 3–4
Physical Changes
Reduced inflammatory burden, early tissue improvements
Performance & Recovery
Improved energy as SASP-driven inflammation decreases
Other Benefits
Skin quality may begin improving
3
Month 2–3
Physical Changes
Improved organ function markers, better skin elasticity
Performance & Recovery
Enhanced physical vitality, reduced joint stiffness
Other Benefits
Cumulative senolytic clearance effects building
4
3+ Months
Physical Changes
Measurable rejuvenation in treated tissues
Performance & Recovery
Sustained improvements in function and resilience
Other Benefits
Typical protocol: 3-day pulses separated by weeks; repeat quarterly

Timeline is illustrative and non-guaranteed. Outcomes vary and are commonly discussed alongside training, nutrition, sleep, and cycling practices.

How It Works

Senolytic Peptide — Selective Senescent Cell Eliminator

Target → Senescent Cell Clearance → Tissue Rejuvenation → Outcomes

🎯
Target

FOXO4-p53 Interaction in Senescent Cells

FOXO4-DRI is a D-retro-inverso peptide that specifically disrupts the interaction between FOXO4 and p53 proteins inside senescent ("zombie") cells. In these damaged cells, FOXO4 sequesters p53 in the nucleus, preventing it from triggering apoptosis. FOXO4-DRI breaks this protective interaction.

Cellular Signal

p53 Release → Mitochondrial Apoptosis Cascade

By displacing FOXO4 from p53, the freed p53 translocates to mitochondria and triggers the intrinsic apoptosis pathway — specifically in senescent cells where this FOXO4-p53 interaction is uniquely present. Healthy cells don't rely on this mechanism, so they are spared.

🔄
Systemic Effect

Senescent Cell Clearance → Reduced SASP → Tissue Rejuvenation

Senescent cells secrete the SASP (Senescence-Associated Secretory Phenotype) — inflammatory cytokines that damage surrounding tissue and accelerate aging. Removing these cells reduces chronic inflammation and allows healthy tissue to regenerate. Mouse studies showed restored fitness, kidney function, and fur density.

What You Notice

Gradual Anti-Aging Effects → Vitality → Tissue Improvement

Effects are cumulative and gradual. Reduced inflammation markers over weeks. Improved tissue function in areas with high senescent cell burden. This is a cutting-edge research compound — no human clinical trials yet. Based on the landmark 2017 Cell paper by Baar et al.

What Makes This Peptide Different

FOXO4-DRI is the most targeted senolytic available — it exploits a vulnerability unique to senescent cells (the FOXO4-p53 nuclear sequestration). Unlike broad senolytics (dasatinib + quercetin) that affect multiple pathways, FOXO4-DRI's D-retro-inverso design makes it protease-resistant while maintaining the specific protein-protein disruption. The selectivity for senescent cells is its key advantage.

Dosing Protocol

Senolytic / Anti-Aging

Educational reference only. Individual responses vary. Consult healthcare provider before use.

Vial Size
5 mg or 10 mg vial
Reconstitution
1-2 mL bacteriostatic water
Dose
5-10 mg per injection (weight-dependent)
Timing
Morning, fasted
Frequency
3 consecutive days per pulse
Duration
3-day pulse, repeat every 2-4 weeks for 2-3 cycles
Protocol Notes
D-retro-inverso peptide — highly protease-resistant. Selectively triggers apoptosis in senescent cells by disrupting FOXO4-p53 interaction. Based on Baar et al. 2017 Cell paper. Allow 2-4 weeks between pulses for immune clearance of apoptotic cells.
Read the full dosing guide — protocols, reconstitution, clinical context & more

Why This Dosing Protocol

Why intermittent dosing? Senolytic therapy doesn't require continuous treatment. Senescent cells accumulate slowly — periodic clearance (hit-and-run approach) is the standard strategy. Short intensive courses followed by long breaks.

Why the D-retro-inverso design? Normal peptides are rapidly degraded by proteases. The DRI modification uses D-amino acids in reverse order, creating a mirror-image peptide that resists enzymatic breakdown while maintaining biological activity.

FOXO4-DRI Pricing

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Reconstitution calculator

Dilution math and unit conversions. Prefilled using a common vial size for this peptide.

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Handling

Educational overview on storage, labeling, and traceability considerations for lab environments. Consult primary literature and vendor documentation for specifics.

Powder Storage (Very Stable)
  • Freezer (-20°C): 1+ year ✓
  • Refrigerator (2-8°C): 1-3 months ✓
  • Room temperature: 2-3 weeks (emergency only)
Reconstituted Storage (Fragile)
  • MUST refrigerate at 2-8°C
  • 4-week maximum shelf life
  • NEVER freeze after reconstitution
  • Use bacteriostatic water for multi-dose

Storage & Handling Guide

Learn proper storage temperatures, shelf life timelines, reconstitution best practices, and travel tips for lyophilized and reconstituted peptides.

Powder: Freezer
1+ year at -20°C
Reconstituted: Fridge
4 weeks max at 2-8°C
View Complete Storage Guide

FAQ

What are senescent cells and why are they harmful?

Senescent cells are damaged cells that stop dividing but refuse to die. They accumulate with age and secrete a toxic cocktail of inflammatory molecules called SASP (senescence-associated secretory phenotype). This chronic inflammation drives aging, tissue dysfunction, and age-related diseases. Clearing these "zombie cells" is the goal of senolytic therapies.

How does FOXO4-DRI selectively target senescent cells?

In senescent cells, the FOXO4 protein binds p53 to prevent apoptosis — keeping the damaged cell alive. FOXO4-DRI competes with endogenous FOXO4 for p53 binding, freeing p53 to trigger the cell's self-destruct program. Healthy cells don't depend on FOXO4-p53 binding for survival, so they're unaffected.

What does D-retro-inverso mean?

D-retro-inverso (DRI) is a peptide engineering technique where the amino acid sequence is reversed and all L-amino acids are replaced with D-amino acids. This makes the peptide highly resistant to proteases (enzymes that break down proteins) while preserving the spatial orientation needed for biological activity. It dramatically extends the peptide's half-life.

What did the original FOXO4-DRI mouse study show?

The landmark 2017 Baar et al. study in Cell showed that FOXO4-DRI restored fitness, fur density, and kidney function in naturally aged mice. It also counteracted chemotherapy-induced senescence. Treated mice showed reduced senescent cell burden and decreased SASP markers without apparent toxicity to healthy tissues.

How is FOXO4-DRI different from dasatinib + quercetin?

Dasatinib + quercetin (D+Q) are broad-spectrum senolytics that affect multiple anti-apoptotic pathways — effective but less selective. FOXO4-DRI specifically disrupts only the FOXO4-p53 survival mechanism unique to senescent cells. This targeted approach may have fewer off-target effects, though D+Q has more human clinical data and is far cheaper (they're repurposed drugs).

How long does reconstituted peptide last?

Once mixed with bacteriostatic water, peptides remain stable for up to 4 weeks when refrigerated at 2-8°C (36-46°F). Unopened powder can last 1+ year in the freezer. Get our complete Storage & Travel Guide.

Is this peptide legal to purchase?

Peptides sold "for research purposes only" are legal to purchase in the US, but are not FDA-approved for human use outside of specific medical applications. Always consult a healthcare provider before use.

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