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Lexicon

MOTS-c

A mitochondrial peptide. Linked to metabolism, insulin sensitivity and training adaptation.

3 min read 15 sources

Still from the explainer video about this entry
Analogue in phase 1 · not approvedLab tested in the shop

No time to read it all? The video sums up the whole entry in about a minute, from how it works to the studies and storage.

Summary

At a glance

Sources checked on 26 Oct 2026

Chain length
16 amino acids

encoded in mitochondrial DNA, described in 20151

In muscle after exercise
11.9 -fold

the body's own MOTS-c in 10 young men after cycling3

Old mice in the fastest running stage
17 %

after two weeks of MOTS-c, none made it without3

In the genetic analysis
27,527 people

a variant in the MOTS-c gene went with more type 2 diabetes in men5

Phase 3 in the registry
0 trials

only one phase 1 trial with an analogue, as of 26 Oct 202614

  • MOTS-c is a peptide of 16 amino acids encoded in the genome of the mitochondria. It was described in 2015.1
  • In cells it slows the folate cycle. As a result the body's own AICAR rises and the energy sensor AMPK switches on. Under stress MOTS-c moves into the cell nucleus.12
  • In mice MOTS-c protected against insulin resistance and diet-induced weight gain. Running performance rose, in old animals too.13
  • In humans there are only measurements of the body's own MOTS-c so far: it rises with exercise and is lower in the blood of older men. Results of controlled trials with injected MOTS-c have not been published.3411
  • MOTS-c is not approved. The registry only lists one completed phase 1 trial with a modified form (analogue). Everything here is the state of research, not a recommendation.14
Profile

Updated May 2026

Class
Mitochondrial-derived peptide

MDP

Route
Subcutaneous
Frequency
2-3x per week

in cycles

Form
Lyophilised powder

reconstituted with BAC water

Sizes
5 to 40 mg

4 sizes in the shop

Contents 16 sections
  1. At a glance
  2. What is MOTS-c?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Injection
  7. Dosing
  8. What the research shows
  9. Research status
  10. Side effects
  11. Practice
  12. Storage
  13. Related compounds
  14. FAQ
  15. Glossary
  16. Sources

What is MOTS-c?

MOTS-c is a short peptide encoded by the DNA of the mitochondria, the power plants of the cell. Such mitochondrial peptides are a relatively young research field. In a research context, MOTS-c is linked to metabolism, insulin sensitivity and adaptation to training.

It is used subcutaneously, dosed in milligrams. It ships as a freeze-dried powder you dissolve in bacteriostatic water.

Comparison

Compared with related compounds

Where each compound acts, as stated in the TPD lexicon. Tap a card to open its entry.

How it works

MOTS-c engages the cell's energy metabolism, among other things via the enzyme switch AMPK, which becomes active under energy shortage and training. In mouse studies this improved insulin sensitivity and protected against diet-induced weight gain and insulin resistance.

Simplified, MOTS-c acts like a signal telling the body to "handle energy more efficiently", similar to what exercise does. Hence the interest in the metabolic and longevity context.

Where it acts

Indirect targets, several organs

Tap a point or a card. Colour = target, grey = effect seen in studies.

  1. Skeletal muscle

    The body's own MOTS-c rose 11.9-fold in muscle after cycling (measurement, nothing given)3

    Observed in trials
  2. Fat tissue

    Brown fat more active, less fat storage (mice)9

    AMPK
  3. Liver

    More fat burning, less fatty liver (mice)8

    Observed in trials
  4. Pancreas

    Fewer aged islet cells, better glucose tolerance (mice)10

    Observed in trials

Targets in the ChEMBL database15

Four recorded mechanisms, type of action on each card.

AMPK, subunit alpha-1
Gene
PRKAA1
UniProt
Q13131
ChEMBL
CHEMBL4045
Action
Activated indirectly via the folate cycle and AICAR
AMPK, subunit alpha-2
Gene
PRKAA2
UniProt
P54646
ChEMBL
CHEMBL2116
Action
Activated indirectly, weaker effect in cells without it
NRF2 (transcription factor)
Gene
NFE2L2
UniProt
Q16236
ChEMBL
CHEMBL1075094
Action
Interaction in the nucleus under stress
HSF1 (heat shock factor)
Gene
HSF1
UniProt
Q00613
ChEMBL
CHEMBL5869
Action
Needed for the stress adaptation of muscle cells
Translucent muscle fibres with glowing yellow mitochondria, next to two blue 3D peptide chains
Symbolic image.

What you need

For subcutaneous use you need:

Supplies

5 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

MOTS-c vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid
  1. MOTS-c vial

    The MOTS-c vial with the freeze-dried powder

    In the shop
  2. Bacteriostatic water

    Bacteriostatic water to dissolve it

    In the shop
  3. U-100 insulin syringes

    U-100 insulin syringes

  4. Alcohol swabs

    Alcohol swabs for the vial cap and the skin

  5. Sharps container

    A sealable sharps container for used needles

As an Amazon associate we earn from qualifying purchases. Links open Amazon - no extra cost for you.

Reconstitution

The powder is dissolved in bacteriostatic water. How much water you add sets the concentration and therefore how many units you draw for your dose on the insulin syringe.

Use the peptide calculator for this: pick your vial size and the water volume to see the concentration and units per dose.

When dissolving, just add the bac water, it does not matter if it hits the powder directly. Then swirl or shake until everything has dissolved, both are fine.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Injection

The injection is subcutaneous, into the fat layer under the skin, classically the abdomen (keep clear of the area around the navel), the front and the inner side of the thigh or the back of the upper arm.

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

What the research shows

The central work (Lee, 2015) described MOTS-c as a mitochondrial peptide that promotes metabolic balance in mice and protects against diet-induced obesity and insulin resistance, mediated via AMPK. That is a strong preclinical basis. Large human studies are still pending, though. That belongs in the picture honestly.

The study with a link is in the source block below.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Fastest running stage reached3

Share of mice that made it to the last, fastest stage of the treadmill test

Young mice, high-fat diet3 Daily dosing, then a treadmill test
Control 17%
Lower study dose 17%
Higher study dose 100%
Old mice (22 months)3 Two weeks of daily dosing
Control 0%
MOTS-c 17%

Values from the full text of the study. Animal experiments with small groups, not transferable to humans. With MOTS-c the old mice also ran twice as long.

Insulin action in the clamp test1

More glucose needed to keep blood sugar stable under insulin, high-fat diet, 7 days

Glucose infusion rate1 Control as the reference (0)
Control 0%
MOTS-c +30%

The study states about 30 percent. The more glucose is needed, the stronger insulin acts. Measured in mice, not in humans.

The body's own MOTS-c during cycling3

Rise compared with baseline, 10 young men

In muscle, after cycling3
Body's own MOTS-c with exercise 11.9-fold
In the blood, during cycling3
Body's own MOTS-c with exercise 1.6-fold

Only measurements of the body's own MOTS-c, without giving MOTS-c. Values from the study, clearly in muscle, less in the blood.

The body's own MOTS-c in the blood4

Healthy men, difference from the young group, measured fasting

Blood level by age4 In muscle, by contrast, MOTS-c was about 1.5-fold higher in the older men
Young (18 to 30 years) 0%
Middle-aged (45 to 55 years) -11%
Older (70 to 81 years) -21%

Observation without giving MOTS-c: only what the body makes itself was measured. Values from the full text of the study.

Row of test tubes in front of a glowing mitochondrion model, next to a running shoe on a bright lab bench
Research on injected MOTS-c in humans is still at the start. Symbolic image.

Research status

Where the research stands

Registered trials with status, participants and results. As of 26 Oct 2026. 14

  1. Preclinical Cell assays and mice
  2. Phase 1 1 trial, 1 completed
  3. Phase 2 no registered trial
  4. Phase 3 no registered trial
  5. Approval not yet
Not approved. The registry only lists one phase 1 trial with an analogue and no phase 2 or 3. ChEMBL does not list MOTS-c.14

Apart from 1 phase 1 trial there is no registered trial in phase 2 or later. 14

Side effects

There is no solid human data on tolerability yet. Mostly mild things are reported: injection-site reactions, occasionally tiredness. Because long-term safety data are missing too, cycles with breaks make more sense than continuous running.

Practice

  1. Run it in cycles over a few weeks, then a break.

  2. Combines well with training, both address energy metabolism.

  3. Sleep and nutrition are the base, MOTS-c builds on that.

White running shoes, a skipping rope and a water bottle on a wooden bench in a bright training room

Storage

The undissolved powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. The reconstituted solution goes into the fridge (2 to 8 degrees) and stays stable there for at least 4 to 6 months with barely any loss of potency, in practice considerably longer. The bacteriostatic water brings a preservative that keeps the dissolved form stable for longer.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed. Keeps for several months without trouble.

Dissolved (mixed) Fridge, 2 to 8 degrees

At least 4 to 6 months with barely any loss of potency. The bacteriostatic water brings a preservative.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.

Related

Related compounds

Same targets, blends with MOTS-c or a different path: all in the TPD lexicon.

FAQ

Common questions about MOTS-c

Short answers, each backed by the sources below.

Is MOTS-c approved?

No. As of 26 October 2026 ClinicalTrials.gov lists no trial in which people receive MOTS-c itself. There was only a phase 1 trial with a modified form (analogue) in healthy adults and people with fatty liver, its results are not in PubMed. There is no phase 2 or 3.1413

What does MOTS-c do in the cell?

It slows the folate cycle and the purine synthesis tied to it. In cells with a lot of MOTS-c the body's own AICAR rose more than 20-fold. AICAR switches on the energy sensor AMPK. Under stress such as glucose shortage MOTS-c moves into the nucleus and regulates genes there, among others together with NRF2.12

What do the animal studies show?

In mice MOTS-c prevented age-related and diet-induced insulin resistance and diet-induced weight gain. In the clamp test insulin action rose by about 30 percent. Old mice ran twice as long after two weeks, 17 percent reached the fastest stage, none without MOTS-c. Lifespan only showed a trend (median plus 6.4 percent), larger studies are missing.13

What is known in humans?

Only measurements of the body's own MOTS-c. In 10 young men it rose 11.9-fold in muscle after cycling and 1.6-fold in the blood during cycling. In the blood of older men it was 21 percent lower than in young men. People with obesity had higher blood levels on average (273 versus 223 pg/ml), after obesity surgery they stayed the same. An Asian-specific gene variant went with more type 2 diabetes in men (27,527 people).3465

How well is MOTS-c tolerated?

That is open. Results of controlled trials with injected MOTS-c in humans have not been published. A 2026 review describes rigorous safety data as scarce.11

What does MOTS-c have to do with exercise?

Exercise makes the body's own MOTS-c rise, clearly in muscle, less in the blood. After endurance exercise a Swedish study found only a trend in the blood. A 2026 systematic review of nine studies mostly saw a trend towards higher levels of mitochondrial peptides but calls the human evidence limited.3712

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

AICAR
Intermediate of purine synthesis that activates AMPK. MOTS-c makes it rise in cells.
AMPK
The cell's energy sensor. It switches on when energy runs low, for example during exercise. It then shifts towards fat burning and glucose uptake.
Folate cycle
Metabolic pathway that supplies building blocks for DNA and purines. MOTS-c slows it in cell experiments.
Insulin resistance
Cells respond less to insulin. Often a precursor of type 2 diabetes.
Insulin sensitivity
How well cells respond to insulin. The higher it is, the less insulin it takes to lower blood sugar.
Longevity
Research on healthy ageing and the processes that steer ageing in the body.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
Mitochondria
The power plants of the cell. They make energy from nutrients and also send out their own signals.
Mitochondrial DNA
The mitochondria's own small genome, separate from the genome in the nucleus. MOTS-c sits in a short reading frame within it.
Mitochondrial-derived peptide (MDP)
Short protein whose blueprint lies in the mitochondrial genome. The best known are humanin and MOTS-c.
NRF2
Switch in the nucleus for protective genes against oxidative stress.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Preclinical
Research in cells and animals before a substance is tested in humans.
Subcutaneous
Into the fat layer just under the skin.
Trial phases
Phase 1 tests tolerability in a few people, phase 2 looks for effect and dose, phase 3 confirms benefit and safety in thousands.

Evidence

Sources

Show all 15 sourcesHide sources 13 Studies1 Trial registry1 Database checked 26 Oct 2026

Studies

  1. Discovery of MOTS-c, metabolism and insulin resistance (mice)

    Lee et al., Cell Metabolism, 2015

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PubMed Central
  2. MOTS-c moves into the nucleus under stress

    Kim et al., Cell Metabolism, 2018

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Exercise, running performance and ageing (humans and mice)

    Reynolds et al., Nature Communications, 2021

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PubMed Central
  4. MOTS-c in blood and muscle of healthy men by age

    D'Souza et al., Aging, 2020

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PubMed Central
  5. Gene variant in the MOTS-c gene and type 2 diabetes

    Zempo et al., Aging, 2021

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. MOTS-c in the blood in obesity and after weight loss

    Yoon et al., Journal of Clinical & Translational Endocrinology, 2026

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. Mitochondrial peptides in the blood after endurance and resistance exercise

    von Walden et al., Journal of Applied Physiology, 2021

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  8. Plasma markers, insulin and fatty liver in obese mice

    Kim et al., Physiological Reports, 2019

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  9. Fat tissue and brown fat after removal of the ovaries (mice)

    Lu et al., Journal of Molecular Medicine, 2019

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  10. Aged pancreatic islet cells (mice)

    Kong et al., Experimental & Molecular Medicine, 2025

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  11. Review: safety of unapproved peptides

    Mendias und Awan, Sports Medicine, 2026

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  12. Systematic review: exercise and mitochondrial peptides

    Ayubi et al., Physiology International, 2026

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  13. Review naming the phase 1 trial with a MOTS-c analogue

    Sousa et al., Biomedicines, 2023

    Checked 26 Oct 2026 via doi.org, Crossref, PubMed, PubMed Central

Trial registry

  1. Trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Target proteins in UniProt and ChEMBL

    UniProt und ChEMBL, EMBL-EBI (MOTS-c selbst nicht in ChEMBL)

    Checked 26 Oct 2026 via UniProt, ChEMBL

In the shop

MOTS-c in the catalog

Sizes, prices and shipping times are on the product page.

To the product