Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Epitalon (Epithalon) | FOXO4-DRI | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates 5-10 mg daily via subcutaneous injection for 10-20 day cycles. | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. |
| Timing | Evening administration preferred (aligns with pineal/melatonin function). Some protocols split doses AM/PM. | No established timing protocol. |
| Cycle Duration | 10-20 day intensive cycles repeated every 4-6 months. Not used continuously. | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. |
| Evidence Level | animal_plus_anecdotal | animal_plus_anecdotal |
Epitalon (Ala-Glu-Asp-Gly / AEDG) is a synthetic tetrapeptide based on the natural pineal gland peptide epithalamin. It activates telomerase by inducing expression of the catalytic subunit hTERT, resulting in telomere elongation averaging 33.3% in human somatic cells. Epitalon restores pineal melatonin synthesis and circadian gene expression in aged organisms, increases BDNF, and upregulates CREB1. It also modulates the neuroendocrine system through its effects on the hypothalamic-pituitary axis and antioxidant enzyme regulation.
Research indicates 5-10 mg daily via subcutaneous injection for 10-20 day cycles.
Evening administration preferred (aligns with pineal/melatonin function). Some protocols split doses AM/PM.
10-20 day intensive cycles repeated every 4-6 months. Not used continuously.
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.
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