Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| DSIP (Delta Sleep-Inducing Peptide) | FOXO4-DRI | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates 100-300 mcg administered before bedtime via subcutaneous injection or intranasal. | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. |
| Timing | 30-60 minutes before desired sleep onset. Evening only. | No established timing protocol. |
| Cycle Duration | 2-4 week cycles with equal rest periods to prevent tolerance. | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. |
| Evidence Level | animal_plus_anecdotal | animal_plus_anecdotal |
DSIP is a naturally occurring nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) originally isolated from rabbit brain hypothalamus in 1977. It modulates GABAergic neurotransmission by potentiating GABA-activated currents in hippocampal and cerebellar neurons while blocking NMDA-activated potentiation in cortical neurons. It also interacts with opioid-associated receptors, modulates serotonin and dopamine systems (increasing serotonin levels), and promotes delta wave (slow-wave) sleep through mechanisms that remain incompletely characterized.
Research indicates 100-300 mcg administered before bedtime via subcutaneous injection or intranasal.
30-60 minutes before desired sleep onset. Evening only.
2-4 week cycles with equal rest periods to prevent tolerance.
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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