Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| FOXO4-DRI | Sermorelin | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. | Research indicates 200-300 mcg administered once daily at bedtime via subcutaneous injection. |
| Timing | No established timing protocol. | Bedtime administration (aligns with natural nocturnal GH release). On empty stomach. |
| Cycle Duration | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. | 12-24 week cycles. Some protocols use continuous treatment. |
| Evidence Level | animal_plus_anecdotal | strong_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.
Sermorelin is a synthetic 29-amino acid peptide representing the biologically active fragment of GHRH (amino acids 1-29) with full functional activity. It activates GHRH receptors on pituitary somatotrophs, stimulating cAMP production via Gs protein/adenylate cyclase and MAP kinase pathways. Due to the interactive effects of sermorelin and endogenous somatostatin, GH release is episodic rather than continuous. Sermorelin also stimulates pituitary gene transcription of GH mRNA, increasing and preserving pituitary GH reserve.
Research indicates 200-300 mcg administered once daily at bedtime via subcutaneous injection.
Bedtime administration (aligns with natural nocturnal GH release). On empty stomach.
12-24 week cycles. Some protocols use continuous treatment.
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