What is MOTS-c?

What is MOTS-c?

MOTS-c is a 16-amino-acid peptide derived from the mitochondria. It activates the AMPK energy-sensing pathway and mimics the metabolic signal of exercise. It is supplied for research purposes in a pre-filled, already-reconstituted multi-dose pen.

It is studied in metabolic and longevity research for its role in mitochondrial function, insulin sensitivity and exercise-mimetic effects. As of 2026 the evidence base comes mostly from cell and animal work; research results vary.

Mechanism of action

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded in mitochondrial DNA, within the 12S ribosomal RNA gene. It was discovered in 2015 and belongs to the family of mitochondria-derived peptides, signals the mitochondria send to the rest of the cell and the organism.

Its main described action is the activation of AMPK, the cell's energy sensor, through the folate pathway and the inhibition of purine synthesis. With AMPK active, glucose uptake in muscle and fatty-acid oxidation increase, the same programme that exercise sets in motion. Under metabolic stress MOTS-c also translocates to the nucleus and regulates stress-response genes.

In humans its plasma and muscle levels rise with acute exercise and fall with age, which has led to it being studied as an exercise mimetic and as a marker of metabolic ageing.

What the published research says

1. 1.
   Lee et al., Cell Metab, 2015PMID 25738459

   The paper that described the peptide. In mice, MOTS-c activated AMPK in muscle, increased glucose uptake and prevented diet-induced obesity and insulin resistance on a high-fat diet.

2. 2.
   Reynolds et al., Nat Commun, 2021PMID 33473109

   MOTS-c rose in the plasma and muscle of young people after exercise. In aged mice, MOTS-c treatment improved physical capacity and endurance, even when started late in life.

3. 3.
   Covarrubias et al., Nat Rev Mol Cell Biol, 2021 (context)PMID 33353981

   Review of the NAD+-sirtuin-mitochondria axis in ageing, the framework in which MOTS-c research is usually placed alongside NAD+.

What side effects does MOTS-c have?

• An energy crash 3–4 hours after the dose is the tell-tale sign of stepping up too far, too soon: it settles once the dose is held until adaptation sets in.
• Fatigue or lethargy at a step the body has not yet acclimatised to.
• Mild, transient injection-site reactions.

How is MOTS-c dosed?

It is titrated up from the lowest step: start at 0.2 mg for two weeks, then climb in 0.2 mg increments (0.4, 0.6, 0.8, 1 mg), never faster than every two weeks and only when the current dose is well tolerated. It is commonly given about 30 minutes before training. The pen sets each step; no mixing is needed.

Storing the pen

Keep the pen between 2 and 8 °C, protected from light and never frozen. Unopened it has a 24-month shelf life; from the first puncture, 12 months. If no fridge is available it keeps for up to 30 days at room temperature, below 30 °C. Let it reach room temperature before giving a dose. The dial sets each dose directly in milligrams: there is no reconstitution, no bacteriostatic water and no volume calculation.

How do you get MOTS-c?

Body Pharm supplies MOTS-c in a sealed, already-reconstituted, HPLC-verified pen with a published certificate of analysis (CoA). Shipping is to Spain only: a single option at €15, delivered in 3–5 working days. It is sold exclusively for research and analytical purposes.

How much does MOTS-c cost per month?

From 139 € per pen: a single 32 mg pen covers a multi-week titration at a few doses a week.

How it compares

As of the last review of this page (October 2026) there are no published clinical trials of MOTS-c administered to people; the evidence is cellular and animal, plus observational data in humans. That is the main difference from NAD+, whose precursors do have randomised trials.

Within the catalogue, MOTS-c is researched as a metabolic signal and NAD+ as a substrate; they tend to appear together in longevity protocols because of that complementarity.

• How to dose MOTS-c
• What is NAD+?
• Peptides for longevity