Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| FOXO4-DRI | GHK-Cu | |
|---|---|---|
| Category | Peptides | Growth Factors |
| Standard Dose | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. | Research indicates 1-2 mg daily via subcutaneous injection, or topical application at 1-3% concentration in cream/serum. |
| Timing | No established timing protocol. | Evening administration preferred for skin rejuvenation (aligns with nocturnal repair cycles). Topical can be applied morning and evening. |
| Cycle Duration | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. | 8-12 weeks for injectable cycles. Topical use can be ongoing. |
| 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-Cu is a naturally occurring copper-binding tripeptide (glycyl-L-histidyl-L-lysine) that modulates gene expression affecting 31.2% of human genes. It activates Wnt/beta-catenin signaling for hair follicle growth, stimulates TGF-beta pathway for tissue remodeling, and promotes collagen and glycosaminoglycan synthesis while modulating metalloproteinase activity. The copper ion serves as a cofactor for enzymes essential to wound healing including superoxide dismutase and lysyl oxidase.
Research indicates 1-2 mg daily via subcutaneous injection, or topical application at 1-3% concentration in cream/serum.
Evening administration preferred for skin rejuvenation (aligns with nocturnal repair cycles). Topical can be applied morning and evening.
8-12 weeks for injectable cycles. Topical use can be ongoing.
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