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FOXO4-DRI (FOXO4-p53 Interfering Peptide)
Also known as: FOXO4-D-Retro-Inverso, Proxofim
Confidence
Updated 2026-03-20
FOXO4-DRI is a modified peptide designed to selectively induce apoptosis in senescent cells. It is a D-retro-inverso (DRI) version of the FOXO4 peptide, engineered for protease resistance and enhanced cell penetration. It has generated enormous interest in the longevity community as a targeted senolytic agent, though human clinical data remains extremely limited.
Class
Senolytic Peptide
Routes
Subcutaneous
Half-Life
Unknown in humans; estimated hours (D-amino acid structure provides protease resistance)
FOXO4-DRI disrupts the FOXO4–p53 interaction that keeps senescent cells alive. In senescent cells, FOXO4 binds and sequesters p53 in the nucleus, preventing p53 from triggering apoptosis. FOXO4-DRI competes for this binding, freeing p53 to translocate to mitochondria and initiate intrinsic apoptosis selectively in senescent cells while leaving healthy cells unaffected.
Half-Life
Unknown in humans; estimated hours (D-amino acid structure provides protease resistance)
Bioavailability
Subcutaneous: estimated moderate (D-retro-inverso peptides have improved stability)
No approved indications. Research interest: selective clearance of senescent cells, age-related tissue dysfunction, chemotherapy-induced senescence, frailty, organ-specific rejuvenation.
De Keizer et al. (Cell, 2017) demonstrated that FOXO4-DRI selectively induced apoptosis in senescent cells in vitro and restored fitness, fur density, and renal function in fast-aging mice. No peer-reviewed human clinical trials have been published. Anecdotal reports from self-experimenters exist but lack scientific rigor. The peptide is very expensive to synthesize due to its large size (~49 amino acids, all D-form).
Human Studies
0
Animal Studies
3
No human safety data. Theoretical concerns: off-target apoptosis if selectivity is imperfect, immune activation from clearance of large numbers of senescent cells, unknown long-term effects of senescent cell depletion. Very expensive — synthesis costs make contamination and purity verification critical.
Investigational only. Not on any regulatory pathway. Available through peptide research suppliers. No GMP-grade pharmaceutical manufacturing. Users assume full risk.
Drug Interactions: Unknown — no human pharmacokinetic data. Theoretical concern with immunosuppressants or chemotherapy agents that induce senescence. Monitoring: No established monitoring protocols. Research groups have used senescence biomarkers (p16INK4a, SA-β-galactosidase) and inflammatory panels. Research Gaps: Human pharmacokinetics entirely unknown. Optimal dosing, cycling, and treatment duration undefined. Whether periodic senolytic dosing or continuous therapy is needed remains unclear.
Subcutaneous (Research Protocol)
Common Range
No established human dose; mouse studies used ~5 mg/kg
Timing
Research protocols only — no clinical dosing established
Frequency
Intermittent dosing hypothesized (senolytic "hit-and-run" approach)
Cycling
No established cycling protocol. Some researchers propose 2–3 day treatment courses separated by weeks.
Important Note
Extremely expensive peptide (~$300–1000+ per dose at research scale). Requires cold chain. D-retro-inverso structure provides protease resistance but complicates synthesis. NOT for clinical use — research only.
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Anti-Aging
Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) studied primarily by Russian researcher Professor Vladimir Khavinson for its potential telomerase-activating and anti-aging properties. It is one of the more speculative peptides in the longevity space, with most data coming from Russian research institutions.
Mitochondrial-Derived Peptide
Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of mitochondrial DNA. It was originally discovered in 2001 during a screen for factors that protect neurons against Alzheimer's disease-related toxicity. Alongside MOTS-c, it is one of the two most studied members of the mitochondrial-derived peptide family and has generated significant interest in longevity and neuroprotection research.
Disclaimer: This content is for educational and informational purposes only and does not constitute medical advice. Always consult with a licensed healthcare provider before starting, stopping, or modifying any peptide therapy. PeptideSupplierMatch does not prescribe, sell, or distribute peptides.
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