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MOTS-c Reference

Educational, not medical advice reference for MOTS-c: Longevity, Metabolic; regulatory status, evidence posture, source review, and schedule not…

Reference summary

The foundational program is Lee 2015 Cell Metabolism (PMID 25738459, 'The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance'), which characterized AMPK activation and folate one-carbon metabolism inhibition (de novo purine synthesis) as the proposed mechanism, with insulin-sensitivity improvement and glucose-uptake increases in skeletal muscle in diet-induced obese mice. Cross-sectional human plasma work shows MOTS-c circulates at low picogram-per-milliliter concentrations, declines with age (about 11 percent lower in middle-aged and about 21 percent lower in older men versus young men), and rises acutely after exercise in some cohorts. No large randomized human outcome trial of exogenous MOTS-c administration has read out.

Regulatory and posture

Categories
Longevity, Metabolic
Aliases
Mitochondrial open reading frame of 12S rRNA type-c, Mitochondrial-derived peptide, MOTSc
Evidence posture
translational - Reproducible rodent metabolic-homeostasis program (Lee 2015) and credible cross-sectional human plasma biology, but no published large randomized human outcome trial of exogenous MOTS-c administration on an obesity, insulin-resistance, or longevity endpoint. Community 'mitochondrial longevity' or 'exercise mimetic' framing outruns the human data.
Regulatory status
No FDA-approved MOTS-c drug label. MOTS-c is a 16-amino-acid peptide (sequence MRWQEMGYIFYPRKLR) encoded within a short open reading frame embedded in the mitochondrial 12S rRNA (MT-RNR1) gene. It is the best-characterized member of the mitochondrial-derived peptide (MDP) family, which also includes humanin (encoded in 16S rRNA / MT-RNR2) and the small humanin-like peptides SHLP1 through SHLP6 (also 16S rRNA). FDA's bulk-substances posture flags peptides marketed for research use; a Pharmacy Compounding Advisory Committee review of MOTS-c was scheduled for 2026 following the April 2026 Category 2 nomination changes. WADA prohibits MOTS-c at all times under category S4.4 (metabolic modulators).
Content review status
research reference

Selected public sources

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