MOTS-c

The MOTS-c evidence base cited here is 8 sources — 1 clinical, 5 preclinical, 1 review. Its strongest evidence is human — a clinical study, most recently 2018 ("Circulating MOTS-c is Decreased in Obese Children and Adolescents"). Regulatory status: Not FDA-approved.

• MOTS-c is a 16-amino-acid MITOCHONDRIAL-derived peptide (MDP) — unusually, it's encoded by mitochondrial DNA (within the 12S rRNA region), not the nuclear genome. It acts as a 'mitohormone' regulating metabolism, insulin sensitivity, and longevity.
• Its core mechanism is AMPK activation (via the folate cycle); under metabolic stress it translocates to the nucleus and binds stress-response transcription factors (NRF2, ATF1/ATF7).
• Exercise itself raises endogenous muscle MOTS-c sharply (~12-fold in humans), which is part of why it's framed as an 'exercise-mimetic' — but the efficacy evidence is overwhelmingly animal, with limited human data.

MOTS-c (Mitochondrial Open reading frame of the 12S rRNA type-c) is one of a small class of mitochondrial-derived peptides — short peptides encoded by mitochondrial rather than nuclear DNA. It behaves like a hormone of cellular energy status, activating the AMPK pathway to improve insulin sensitivity, metabolic flexibility, and stress resistance.

It is investigational and not FDA-approved, and it's banned in sport. Everything below is research context, not medical guidance.

MOTS-c is a 16-residue peptide (~2,175 Da, sequence MRWQEMGYIFYPRKLR) encoded by the MT-RNR1 gene inside the mitochondrial 12S rRNA region. Its mitochondrial origin is genuinely unusual — most signaling peptides come from the nuclear genome — and it's part of why it's studied as a direct readout of mitochondrial health.

If you're verifying a vendor's product, the COA should confirm that exact sequence (MRWQEMGYIFYPRKLR) and >95% purity by RP-HPLC.

MOTS-c inhibits the folate cycle, which raises AICAR and activates AMPK — the master energy-sensing kinase that, when on, promotes glucose uptake, fat oxidation, and mitochondrial biogenesis (the same pathway metformin and exercise engage). Under metabolic stress, MOTS-c also translocates to the nucleus and binds stress-response transcription factors (NRF2 for antioxidant defense, ATF1/ATF7), coordinating a broader metabolic and stress-adaptation program. In animals this improves insulin sensitivity (~30% in some models) and can prevent diet-induced obesity at matched calorie intake.

• Time to peak: ~1 hour
• Half-life: ~4 hours
• Largely cleared within ~20 hours (Lee et al., 2015 — the foundational MOTS-c discovery paper)

There is no approved dosing. Figures below are research/anecdotal, included for context only.

• Metabolic health: ~5–10 mg once daily, subcutaneous
• Anti-aging: ~15 mg 3× weekly; exercise: ~10–15 mg pre-workout
• Conservative start: ~5 mg once daily
• AMPK activation is reported within ~30 minutes; morning/pre-exercise timing is common

• Reconstitute with bacteriostatic water down the vial wall; swirl gently, never shake; solution should be clear.
• Reconstituted: refrigerate at 2–8°C, use within ~14 days. Lyophilized: stable ~3 weeks at room temperature, longer frozen.
• Verify with a COA confirming the MRWQEMGYIFYPRKLR sequence and >95% purity.

Well-tolerated in animal studies, with mild injection-site reactions the main reported effect. Because it lowers glucose via AMPK, monitor blood glucose if combined with diabetes medications (metformin, sulfonylureas) — the effect is additive. Long-term human safety data is limited, and it is not recommended in pregnancy/breastfeeding. It is WADA-prohibited for competitive athletes.

• MOTS-c discovery (Lee et al., 2015): identified the peptide and its AMPK/insulin-sensitizing role — the foundational reference.
• Exercise performance & age-dependent decline (2021, Reynolds et al., mice + humans): enhanced performance across ages; documented the ~12-fold exercise-induced rise in human muscle MOTS-c.
• Acute exercise enhancement (2022, mice/rats, 15 mg/kg IV): improved running time and distance.

MOTS-c is not FDA-approved and is sold as a research chemical for laboratory use only, not intended for human consumption. It is on the WADA Prohibited List as an AMPK-activating metabolic modulator.

All citations link to the original source (PubMed, journal site, or regulatory filing). Independent research database — no vendor influence on what's cited.