Pentapeptide-18 vs FOXO4-DRI
Side-by-side comparison of key properties, dosing, and research.
Skin & CosmeticAnti-Aging & Longevity
Pentapeptide-18Anti-Aging & Longevity
FOXO4-DRI- Summary
- Pentapeptide-18 (Leuphasyl) is a synthetic pentapeptide that mimics the sequence of enkephalin, an endogenous neuropeptide. It acts on neuronal pain receptors in facial muscles to reduce muscle contraction intensity and depth of expression lines, functioning similarly to Argireline (Acetyl Hexapeptide-3) but via a different receptor mechanism.
- FOXO4-DRI is a D-retro-inverso peptide derived from the FOXO4 protein that selectively induces apoptosis in senescent cells. By disrupting the FOXO4-p53 interaction that keeps senescent cells alive, it triggers programmed cell death specifically in these aging, pro-inflammatory cells while sparing healthy tissue.
- Half-Life
- Not applicable (topical)
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- Admin Route
- Topical
- Subcutaneous, Intraperitoneal (research)
- Research
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- Typical Dose
- 0.005–0.05% in formulation
- 5 mg/kg in rodent studies; human equivalent approximately 0.5-1 mg/kg
- Frequency
- Twice daily
- 3 consecutive days per cycle
- Key Benefits
- Reduces depth of expression lines (forehead, crow's feet, glabellar)
- Inhibits acetylcholine release for muscle-relaxing effect
- Complementary mechanism to Argireline for enhanced anti-wrinkle activity
- Reversible and well-tolerated
- No risk of systemic paralysis at cosmetic concentrations
- Suitable for daily use in serums and creams
- Selectively clears senescent cells (senolytics)
- Reduces senescence-associated secretory phenotype (SASP) and chronic inflammation
- Demonstrated restoration of physical fitness in aged mice
- May improve healthspan and reduce age-related tissue dysfunction
- Potential for treatment of age-related pathologies driven by cellular senescence
- Does not affect healthy non-senescent cells at therapeutic doses
- Side Effects
- Generally very well-tolerated topically
- Rare skin sensitivity or mild irritation
- Theoretical opioid receptor desensitization with very prolonged high-dose use (not documented cosmetically)
- Limited human data; largely preclinical evidence
- Possible temporary inflammatory response as senescent cells are cleared (senolytic effect)
- Weight loss observed at high doses in rodent studies
- Unknown long-term safety profile in humans
- Stacks With
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