P21 vs FOXO4-DRI
Side-by-side comparison of key properties, dosing, and research.
- Summary
- P21 is a synthetic peptide derived from CNTF (ciliary neurotrophic factor) that promotes hippocampal neurogenesis, enhances memory and spatial learning, and may reduce amyloid-beta pathology. It is used as a neurogenic and cognitive enhancer with potential anti-Alzheimer's applications.
- 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 well characterized; likely short, but neurogenic effects persist long after administration
- Estimated 2-4 hours (D-amino acid confers resistance to proteolysis)
- Admin Route
- SubQ, Intranasal
- Subcutaneous, Intraperitoneal (research)
- Research
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- Typical Dose
- 100–500 mcg
- 5 mg/kg in rodent studies; human equivalent approximately 0.5-1 mg/kg
- Frequency
- Once daily
- 3 consecutive days per cycle
- Key Benefits
- Promotes hippocampal neurogenesis
- Enhances spatial memory and learning
- Increases BDNF expression
- Reduces amyloid-beta plaque formation (animal models)
- Anti-tau pathology potential
- Cognitive enhancement without stimulant effects
- Potential therapeutic for Alzheimer's and cognitive aging
- 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 well tolerated in animal studies
- Limited human clinical data
- Injection site reactions
- Potential mild fatigue at initiation
- 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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