Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| FOXO4-DRI | Humanin | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. | Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established. |
| Timing | No established timing protocol. | No established timing protocol. Morning dosing suggested for neuroprotective applications. |
| Cycle Duration | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. | Experimental — no established cycle lengths. |
| 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.
Humanin is a 24-amino acid mitochondrial-derived peptide encoded by the 16S rRNA gene of mitochondrial DNA. It binds IGFBP-3 with high affinity (via Phe-6), interfering with IGFBP-3 binding to importin-beta and suppressing IGFBP-3-mediated apoptosis. It also inhibits the pro-apoptotic protein Bax (Bcl-2 family), preventing mitochondrial outer membrane permeabilization and intrinsic apoptosis. Humanin and IGFBP-3 synergistically protect neurons from amyloid-beta-induced apoptosis, and it activates the STAT3 and ERK1/2 pathways for cytoprotection.
Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.
No established timing protocol. Morning dosing suggested for neuroprotective applications.
Experimental — no established cycle lengths.
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