What it is

Peptides acting on it

Evidence

  • [educational] Longevity angle: MOTS-C ‘trains’ mitochondria via AMPK, SS-31 gives structural (cardiolipin) support, and GLP-1 agonists also improve mito function/↓oxidative stress — all targeting mitochondrial dysfunction as a hallmark of aging. — Longevity Top-5

  • [educational] MOTS-C drives the AMPK → SIRT1 → PGC-1α axis (mito biogenesis, fat/glucose handling) and inhibits NF-κB — the molecular basis of mitohormesis (‘exercise in a vial’); it favors endurance (slow-twitch) adaptations. — MOTS-C deep dive

  • [educational] Two complementary mito strategies: SS-31 stabilizes structure (cardiolipin/ETC → ↑ATP, ↓ROS) while MOTS-C signals adaptation (AMPK/mitohormesis). SS-31 carries no overstress risk; MOTS-C does. — SS-31 deep dive

  • [literature] First registered human RCT of a mitochondrial-derived peptide (2026): MOTS-C Phase 2a NCT07505745 tests OGTT-derived insulin sensitivity (Matsuda Index) in prediabetes + overweight/obesity — the AMPK/mitohormesis thesis moving from preclinical into a controlled human metabolic endpoint. Recruiting, no results. — SOURCE-motsc-prediabetes-phase2a-nct07505745