Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Humanin | MOTS-c | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established. | Research indicates 5-10 mg administered 3-5 times per week via subcutaneous injection. |
| Timing | No established timing protocol. Morning dosing suggested for neuroprotective applications. | Morning administration preferred. Can be dosed pre-workout for enhanced exercise performance. |
| Cycle Duration | Experimental — no established cycle lengths. | 8-16 week cycles. |
| Evidence Level | animal_plus_anecdotal | Emerging (strong preclinical) |
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.
MOTS-c is a 16-amino acid mitochondrial-derived peptide encoded by the 12S rRNA gene of the mitochondrial genome. It primarily acts through the folate-AICAR-AMPK pathway: by regulating the folate cycle and de novo purine biosynthesis, it increases AICAR accumulation, which phosphorylates and activates AMPK. This enhances glucose uptake in skeletal muscle, improves insulin sensitivity, and mimics exercise-mediated physiological responses. Skeletal muscle MOTS-c levels increase 11.9-fold in response to acute exercise in young men.
Research indicates 5-10 mg administered 3-5 times per week via subcutaneous injection.
Morning administration preferred. Can be dosed pre-workout for enhanced exercise performance.
8-16 week cycles.
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