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Evidence-rated reference Updated August 2026
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Research Use Only Longevity & Mitochondrial Evidence 1/5 · Minimal

MOTS-c

Also known as Mitochondrial ORF of the 12S rRNA type-c

Mitochondrial-derived peptide — 16 amino acids encoded in mitochondrial DNA

Overview

A genuinely interesting discovery — a hormone encoded by the mitochondrial genome rather than the nucleus. The exercise-mimetic and metabolic findings in mice are striking. Human data begins and ends with observational plasma-level associations.

Not approved for human use anywhereNo approval anywhere for human use. Sold under research-use labelling. Not approved for human use.

At a glance
Regulatory statusNot approved. Active academic research subject; no completed human efficacy trials.
Drug classMitochondrial-derived peptide — 16 amino acids encoded in mitochondrial DNA
RouteSubcutaneous (research)
Half-lifeShort; not well characterised in humans
Evidence rating
1/5 Minimal Evidence rating 1 out of 5: Minimal
Animal or laboratory data only. No human efficacy evidence.
Studied inMouse metabolic and exercise studies; human observational work correlating plasma MOTS-c with metabolic health, exercise and longevity phenotypes.

How it works

Translocates to the nucleus under metabolic stress and regulates adaptive nuclear gene expression, notably via AMPK activation and the folate-methionine cycle. Improves insulin sensitivity and glucose utilisation in skeletal muscle in animal models.

Evidence base

Rated 1 of 5 — Minimal. Animal or laboratory data only. No human efficacy evidence.

  • Legitimate and active academic science; zero human interventional evidence.

Benefits & potential uses

Bars indicate how well each claim is supported: three = strong human evidence, two = moderate, one = preliminary or preclinical.

  • Improved insulin sensitivity in mice Preliminary

    Reverses diet-induced insulin resistance and obesity in rodent models.

  • Exercise-mimetic effects in animals Preliminary

    Improves running capacity and muscle metabolic function in aged mice.

  • Association with longevity variants Preliminary

    A mitochondrial DNA variant affecting MOTS-c is associated with exceptional longevity in a Japanese population — a real human genetic finding.

  • Rises with exercise in humans Preliminary

    Plasma MOTS-c increases acutely with exercise, consistent with a role in metabolic adaptation.

Risks, cons & cautions

Bars indicate seriousness: three = serious or common, two = moderate, one = minor.

  • No human interventional trials Serious

    Nobody has run a controlled trial of administering MOTS-c to people. All human data is correlational.

  • Unknown dosing and pharmacokinetics Serious

    Circulating protocols are invented, not derived from human PK data.

  • Broad transcriptional effects Moderate evidence

    A peptide that alters nuclear gene expression programs has correspondingly broad potential for unintended consequences.

  • Unregulated supply Serious

    Research-chemical market.

Who should avoid it

  • Human use outside research settings

If used under medical supervision, monitor

  • No validated monitoring exists

Not approved for human use.

Infographic

MOTS-c — benefits & risks at a glance Download SVG
Infographic summarising the benefits and risks of MOTS-c, from pepteyes.com

Where to read further

We link to live literature searches rather than a frozen citation list, so you always see current results — including anything published after our last review.

mitochondriametabolicexercise mimeticlongevitypreclinical only

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Terms used on this page

Insulin Resistance
Insulin resistance is a state in which a given insulin concentration produces less than the expected effect on glucose uptake, hepatic glucose output or lipolysis.
Preclinical Study and Animal Model
Preclinical studies are the laboratory, cell and animal experiments done before any human exposure, establishing mechanism, target engagement and the toxicology package that permits a first trial.
Metabolic Adaptation
Metabolic adaptation is the fall in energy expenditure after weight loss that exceeds what the smaller body size and composition alone would predict.
Randomised Controlled Trial (RCT)
A randomised controlled trial assigns participants to intervention or control by chance and follows them prospectively, which is what allows an outcome difference to be attributed to the treatment itself.

This page is educational information, not medical advice. It cannot account for your medical history, medications, or risk factors. Do not start, stop or change any treatment based on it. Speak to a qualified healthcare professional who knows your case.