MOTS-c
Mitochondrial-derived peptide (16 aa, encoded in mtDNA)
- Class
- Mitochondrial peptide
- Half-life
- Short
- Route
- Subcutaneous (SubQ)
- Cadence
- Multiple per week
- Evidence
- Animal data primarily
Overview
MOTS-c is a 16-amino-acid peptide that's unusual for one big reason: it's encoded inside your mitochondria, not your regular DNA. Mitochondria are the energy factories in your cells, and they have their own tiny genome — MOTS-c is one of a small handful of peptides made from that genome that act like signalling molecules.
In mice, MOTS-c looks like an exercise mimetic — it activates AMPK (the same energy-sensing switch that exercise and metformin hit), improves insulin sensitivity, and protects against age-related metabolic decline. Your body's natural MOTS-c levels drop as you age and are lower in people with type-2 diabetes, which has fuelled interest in injecting it as an anti-ageing intervention.
Reality check: human trials in 2026 are essentially just safety / pharmacokinetic data. There's no big efficacy trial that says "this works in humans the way it does in mice." The longevity-community use is extrapolated from rodent studies. Promising? Yes. Proven? No.
Update: As of mid-2026, a Phase 2a randomized, double-blind, placebo-controlled trial (NCT07505745) is underway testing MOTS-c in adults with prediabetes and overweight/obesity. Primary endpoints are insulin sensitivity (Matsuda Index) and safety over 16 weeks. Results are pending, but this represents the first controlled human efficacy trial.
Safety considerations
A few of the safety signals worth knowing — the full list, with dosing context and what to monitor, is inside AIx Core.
- Not approved for human use anywhere. Human safety data is limited to early-phase PK studies — short-term, small N.
- Mechanism overlaps with metformin and similar AMPK activators. If you're already on a glucose-lowering drug, the combination risk for low blood sugar is real.
- Long-term safety of injecting a mitochondrial-derived peptide is genuinely unknown. The body makes its own, but injecting synthetic versions at supraphysiological doses is a different question.
+ 3 more safety notes inside AIx Core →
Commonly monitored
Markers and signals people track when researching MOTS-c.
- Fasting glucose / HbA1c — the primary signal of metabolic effect
- Insulin / HOMA-IR if you can get it (assess insulin sensitivity)
- Lipid panel — most reported benefit
- Exercise capacity / VO₂ max if you're a tracking athlete (the exercise-mimetic claim)
Frequently asked questions
What is MOTS-c?
Mitochondrial-derived peptide (16 aa, encoded in mtDNA). MOTS-c is a 16-amino-acid peptide that's unusual for one big reason: it's encoded inside your mitochondria, not your regular DNA. Mitochondria are the energy factories in your cells, and they have their own tiny genome — MOTS-c is one of a small handful of peptides made from that genome that act like signalling molecules.
How is MOTS-c administered?
Subcutaneous (SubQ), typically multiple per week.
What is the half-life of MOTS-c?
Short — Cleared from blood in hours, but effects inside cells last longer.
Is MOTS-c approved for human use?
MOTS-c is investigational — not approved by the FDA, EMA, or MHRA for human use at the time of writing.
What does the evidence show for MOTS-c?
Evidence tier: Animal data primarily. Lee 2015 (Cell Metab) — the discovery paper. Established that MOTS-c exists as an actual physiological molecule, activates AMPK in mouse skeletal muscle, and that exogenous dosing reverses age-related insulin resistance in mice. This is the foundational paper.
What is commonly monitored when researching MOTS-c?
Commonly tracked markers + signals: Fasting glucose / HbA1c — the primary signal of metabolic effect, Insulin / HOMA-IR if you can get it (assess insulin sensitivity), Lipid panel — most reported benefit, Exercise capacity / VO₂ max if you're a tracking athlete (the exercise-mimetic claim).
Related compounds
Open this in AIx Core for the full picture
Mechanism breakdown, receptor pathway diagram, full safety list, monitored items, source citations, and one-tap add-to-protocol. Free with any account.