Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| FOXO4-DRI | GHK (without copper) | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. | Research indicates 1-3% concentration in topical formulations. Injectable dosing follows GHK-Cu protocols at 1-2 mg daily. |
| Timing | No established timing protocol. | Topical application morning and evening. Injectable in evening. |
| Cycle Duration | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. | Topical use can be ongoing indefinitely. Injectable cycles 8-12 weeks. |
| Evidence Level | animal_plus_anecdotal | moderate_human |
FOXO4-DRI is a D-retro-inverso peptide that selectively targets the FOXO4-p53 protein-protein interaction in senescent cells. In senescence, FOXO4 binds p53's disordered transactivation domain (TAD2) in the nucleus, preventing p53 from translocating to mitochondria where it would trigger apoptosis. FOXO4-DRI competitively disrupts this interaction, causing nuclear exclusion of p53 and its redirection to mitochondria, selectively inducing apoptosis in senescent cells while sparing healthy cells. The D-retro-inverso configuration provides protease resistance.
Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly.
No established timing protocol.
Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established.
GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring tripeptide found in human plasma, saliva, and urine that has an extremely high affinity for copper(II) ions. Even without exogenously complexed copper, GHK rapidly chelates available copper in biological systems, making copper-free GHK functionally similar to GHK-Cu in vivo. The peptide stimulates collagen and glycosaminoglycan synthesis, modulates metalloproteinase activity, resets gene expression patterns toward a healthier state (affecting 31.2% of human genes), and activates wound healing cascades.
Research indicates 1-3% concentration in topical formulations. Injectable dosing follows GHK-Cu protocols at 1-2 mg daily.
Topical application morning and evening. Injectable in evening.
Topical use can be ongoing indefinitely. Injectable cycles 8-12 weeks.
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