MOTS-c

evidence score

peptide

Research Only

281 studies

mitochondrial open reading frame of the 12S rRNA-cMOTS c peptide

MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome (12S rRNA region), making it the first mitochondria-derived peptide identified. It acts as a metabolic regulator, improving insulin sensitivity, activating AMPK, and mimicking exercise adaptations. Circulating levels decline with age and in metabolic disease. Animal data shows reversal of diet-induced obesity, improved glucose tolerance, and extended lifespan. Currently in early Phase I human trials. Compelling candidate for metabolic disease, longevity, and performance.

Evidence

Moderate evidence

Safety

Unknown safety profile

Clinical Status

Preclinical

Research Sync

Feb 19, 2026

Dosing

Typical

10 mg

5 mgRange15 mg

FrequencyDaily or 5x/week subcutaneous (research dosing from animal studies)

Set height & weight in Settings to see your dose.

Pharmacology

Half-lifeUnknown in humans; hours estimated

OnsetDays to weeks in animal models

DurationOngoing dosing required for sustained effects

Routes

subcutaneous

intravenous

Evidence Score

Level B — Moderate

281 studies indexed · 1 meta-analysis

Scoring Factors

Volume(40%)~49/100

Quality(30%)~44/100

Sample Size(10%)~100/100

Consistency(10%)~100/100

Replication(5%)~100/100

Recency(5%)~100/100

Scores estimated from study counts. Exact breakdown computed after research sync.

Evidence Levels

AScore ≥75 with at least 1 meta-analysis and 3+ RCTs

BScore ≥50 with at least 1 RCT or meta-analysis

CScore ≥25 — observational or animal evidence only

DScore <25 — very limited or preclinical data

Plain-English Snapshot

MOTS-c is currently categorized as a peptide compound.

Evidence is moderate (67/100): promising signal from 281 indexed studies, but context and population still matter.

Safety scoring is incomplete. Start conservatively and monitor carefully.

Core mechanism

Mitochondria-to-nucleus retrograde signaling via AMPK and AICAR; improves insulin sensitivity, metabolic flexibility, and exercise capacity

Practical Context

Strongest current signals

Level C: Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review).
Level D: 0.5 mg/kg is identified as the optimal cardioprotective dose within the tested range, producing coordinated anti-apoptotic, antioxidant, and anti-inflammatory effects.
Level D: MOTS‑c protects against placental injury via Nrf2 activation in hypoxia‑induced intrauterine growth restriction mice.