Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| FOXO4-DRI | LL-37 (Cathelicidin) | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. | Research indicates 50-100 mcg daily via subcutaneous injection for immune support. |
| Timing | No established timing protocol. | Morning administration preferred for immune support. Topical application directly to wound sites. |
| Cycle Duration | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. | 4-8 week cycles. Short-term use preferred due to limited long-term safety data. |
| Evidence Level | animal_plus_anecdotal | animal_plus_anecdotal |
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.
LL-37 is a 37-residue amphipathic helical antimicrobial peptide, the only human cathelicidin, that kills bacteria by forming tetrameric channels that perforate cytoplasmic membranes. Beyond direct antimicrobial activity, it modulates innate immunity through formyl-peptide receptor 2 (FPR2), induces chemotaxis of neutrophils and monocytes, upregulates CXCR4 and IL-8, and neutralizes bacterial endotoxins (LPS). It also promotes wound healing through keratinocyte migration and angiogenesis.
Research indicates 50-100 mcg daily via subcutaneous injection for immune support.
Morning administration preferred for immune support. Topical application directly to wound sites.
4-8 week cycles. Short-term use preferred due to limited long-term safety data.
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