MOTS-c
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 24-amino-acid peptide encoded by mitochondrial DNA (mtDNA), acting as an exercise mimetic and metabolic regulator. Exercise-induced (↑5–10x), it enhances insulin sensitivity, fat oxidation, and AMPK activation—mimicking fasting/CR. Research targets obesity, T2D, aging, and neurodegeneration; mouse lifespan +10–20%.
Origin: mt-tRF (tRNA fragment); serum ↑ post-HIIT.
Mechanism
- Nuclear Signaling: Enters nucleus → FOLR1 → AMPK → glucose uptake.
- Metabolic Switch: ↑PDK4, ↓mTORC1 → fat burning.
- Mito Biogenesis: PGC-1α synergy.
- Stress Resistance: ROS balance, autophagy.
PK: SubQ/oral research; half-life ~hours.
Research Evidence
| Model/Effect | Studies/Outcomes |
|---|---|
| Obesity/Diabetes | -10% BW, insulin sensitivity 2x (mice, Cell Metab 2015). |
| Exercise Mimic | Endurance ↑50%, AMPK = HIIT (FRCP1 KO). |
| Aging | Muscle function preserved, frailty ↓ (aged mice). |
| Neuro | Alzheimer’s models: Aβ clearance ↑. |
| Cancer | mTOR ↓ → proliferation block. |
Protocols (Research Contexts)
| Goal | Dose (mcg/day) | Route/Frequency | Cycle |
|---|---|---|---|
| Metabolism | 5–10 | SubQ AM | 8–12 weeks |
| Fat Loss | 10–15 | Fasted daily | 12 weeks |
| Longevity | 5 | Alternate day | Long-term |
| Performance | 10–20 | Pre-WO | 6 weeks on/2 off |
- Stack: w/ SS-31 (mito), 7-Keto DHEA.
- Source: Synthetic mtDNA-derived.
Benefits
- Insulin Sensitivity: T2D reversal potential.
- Fat Adaptation: Keto-like without diet.
- Muscle Preservation: Sarcopenia shield.
- Brain Health: Cognitive resilience.
- Exercise Boost: HIIT amplifier.
Side Effects & Safety
| Reported | Theoretical | Notes |
|---|---|---|
| None significant | AMPK overactivation | Clean preclinical |
| Mild fatigue | None | Self-resolves |
Comparisons
| Peptide | Origin | Metabolic Effect | Mimics |
|---|---|---|---|
| MOTS-c | mtDNA | Insulin/AMPK | Exercise |
| Humanin | mtDNA | Cytoprotect | Stress |
| SS-31 | Synthetic | Mito ROS | Cardiolipin |
| SHLP2 | mtDNA | Muscle/fat | Aging |
Status & Outlook
- Research Chemical: Human trials Phase 1 (CohBar).
- UK: Academic synthesis.
- Future: T2D/obesity 2027+.
Disclaimer: Experimental research only.
| QUANTITY | 10mg, 40mg |
|---|
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