MOTS-c — identity, handling and published literature

A 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region, supplied as a 20 mg lyophilised solid for laboratory research use.

Presentation and physical properties

Reconstitution arithmetic for this vial

Concentration follows directly from the fill mass and the volume of diluent added:

concentration (mg/mL) = vial mass (mg) ÷ diluent volume (mL)

For this vial the fill mass is 20 mg. The third column restates the same concentration against the graduations of a 100-unit measure, where one unit is 0.01 mL.

The arithmetic is arithmetic. It states how much peptide is present in a given volume of the solution that has been made; it does not indicate an amount to be used, and this library publishes no target amount, frequency or protocol for any compound.

Open the reconstitution calculator with this vial selected. The calculator carries vial strengths only.

Storage and stability

Sealed lyophilised solid: store at −20 °C or below, desiccated and protected from light. Short periods at 2–8 °C in transit do not affect lyophilised material. The vial is equilibrated to room temperature before opening, so that atmospheric moisture does not condense onto the cake.

Once in solution: store at 2–8 °C and do not freeze. Solutions of this peptide are substantially less stable than the solid, and freeze–thaw cycling is avoided.

Oxidation is the specific stability issue for this molecule rather than a generic caution. Two methionine residues and one tryptophan are present, and those are among the most oxidation-prone residues in peptide chemistry, so headspace oxygen, transition-metal contamination and light exposure all matter more here than they would for a peptide without them. Methionine sulfoxide formation appears as a +16 Da satellite in mass spectrometry, which is the standard analytical tell — see the next section.

On the twenty-eight day convention often quoted for a reconstituted vial that will be entered more than once: that interval derives from the preservative in bacteriostatic water and its ability to hold back microbial growth in a repeatedly entered container. It is a statement about the diluent, not about the peptide. For a molecule with this residue set, chemical stability in solution is the shorter constraint of the two, and the preservative interval should not be read as a shelf life for the dissolved material.

Analytical identity and certificate literacy

Identity and purity for this compound are ordinarily established by reversed-phase HPLC for purity and by ESI-MS or MALDI-TOF for mass confirmation. Circulating MOTS-c in human studies is typically measured by immunoassay or LC-MS/MS, which is a different problem and a different method from confirming a solid.

Expected masses

Because the molecule is strongly basic, positive-mode electrospray tends to produce a multiply charged envelope rather than a dominant singly charged ion; a spectrum showing only a small [M+H]⁺ is expected behaviour and not a fault.

What a purity figure does and does not measure

An HPLC purity figure is an area percentage: the proportion of ultraviolet-absorbing material eluting in the main peak, at a stated wavelength, under one stated method. It says how much of the peptide-like material present is the target peptide. It says nothing about how much of the weighed solid is peptide at all, because water, counter-ion and residual salts do not absorb at the detection wavelength and therefore never appear in the integration.

Net peptide content is the separate figure that answers that question, determined by amino acid analysis or nitrogen determination. For an acetate salt of a strongly basic peptide it is materially below 100 per cent, because counter-ion and bound water make up part of the weighed mass. Two certificates can both read “greater than 99 per cent” and describe solids with different peptide content, if one reports area percentage and the other reports net peptide content. Reading which figure is which is the single most useful piece of certificate literacy in this category.

Lot-to-certificate traceability is the third question, and it is the one most often skipped: a certificate is only evidence about the material in hand if its lot identifier can be matched to that material. Where a lot identifier is not printed on the vial itself, traceability rests on the despatch record rather than on the label, which is a weaker chain and worth knowing about before a certificate is relied upon.

What the published literature investigated

Each entry below states what a study investigated, in what model, and what its authors reported. Entries are grouped by model class. No synthesis across studies is offered here and none should be inferred; the studies were conducted in different models, by different groups, with different endpoints.

In vitro

• Xing and colleagues (2026) investigated the effect of MOTS-c on metabolic signalling and on reparative function in human mesenchymal stromal cells, and reported activation of metabolic signalling accompanied by a blunting of reparative function in those cells. The authors’ result runs counter to the direction reported in much of the remaining literature, and is recorded here for that reason. [4]

Rodent models

• Lee and colleagues (2015) investigated a peptide product predicted from a short open reading frame within the mitochondrial 12S rRNA, in cell culture and in mouse models including diet-induced obesity, and reported the identification of that open reading frame and its peptide product, effects on the metabolic parameters they measured in those mouse models, and a proposed mechanism involving the folate and methionine one-carbon cycle and AMPK activation. This is the foundational identification paper for the compound. [1]
• Reynolds, Lai, Woodhead and colleagues (2021) investigated whether MOTS-c is exercise-responsive and how it relates to age-dependent physical decline and muscle homeostasis, in young, middle-aged and old mice with accompanying human exercise measurements, and reported that MOTS-c was induced by exercise and that physical performance measures were higher in the mice studied under the conditions they tested. [2]
• Mills, de Souza, Pham and Mugisho (2026) investigated systemic and cardiac inflammasome activation in a high-fat diet plus streptozotocin model of type 2 diabetes in rats, and reported lower fasting blood glucose and circulating C-reactive protein, selective modulation of plasma IL-10 and IL-1β, and decreased NLRP3, ASC and cleaved caspase-1 in left ventricular tissue in that model. [3]

Non-rodent animal models

No study in a non-rodent animal model is recorded in the sources listed for this entry at the date of last review.

Human studies

• Horwath and colleagues (2026) measured circulating mitochondrial-derived microproteins at rest and following a single bout of endurance exercise, in an observational human study of individuals with cerebral palsy and comparison participants, and reported the concentrations observed at rest and their response to that exercise bout in the groups studied. [6]
• Reference [2] also includes human exercise measurements alongside its rodent work.

Both are measurements of endogenous circulating concentrations. No published study in which MOTS-c itself was administered to human participants is recorded in these sources. The one human clinical programme in this area tested a different molecule and is described under evidence gaps below.

Model class not established from the source record

• Santhanam and colleagues (2026) investigated mitochondrial subpopulation bioenergetics and mitochondrial genome integrity in an experimental cardiac ischaemia–reperfusion model, and reported preservation of both in the model they used. The species used is not stated in the record held for this entry, so the study is placed here rather than assigned to a model class it may not belong to; this will be resolved at the next review. [5]

Evidence gaps and limitations

This is the section that matters most on this page, and it is deliberately not softened.

• No human trial of MOTS-c exists. Not one. Every entry in the literature section above is either an animal model, a cell model, or an observational measurement of concentrations the body already produces.
• The single human clinical programme tested a different molecule. It examined CB4211, an analogue, not MOTS-c. It was Phase 1, it enrolled 20 participants at the efficacy stage, and it showed no effect on its imaging endpoint: hepatic fat fell 5.03 per cent on drug against 4.88 per cent on placebo. The sponsoring company subsequently dissolved. [7]
• No human pharmacokinetics, and no dose-finding. Neither has been published for the native peptide.
• No evidence of tissue exposure. There is no published evidence that exogenously supplied MOTS-c reaches any relevant tissue compartment in humans.
• Association is not causation in the observational literature. Reports that endogenous concentrations differ between population groups describe correlations in cross-sectional data. They establish nothing about what supplying the peptide from outside would do.
• No toxicology to regulatory standard. No systematic human safety database exists for native MOTS-c, and the FDA has recorded an immunogenicity concern for compounded preparations containing it. [8]
• Effect sizes are not established for any endpoint in humans, because no human administration study has been conducted from which to estimate one.

Regulatory and standards position

MOTS-c is not a licensed medicine in the United Kingdom and holds no UK marketing authorisation. It is not FDA-approved. It appears on the FDA’s bulk-substance records under nominated-but-withdrawn, with the FDA noting that compounded drugs containing it “may pose significant risk for immunogenicity”. Under the World Anti-Doping Code it falls within the S0 catch-all for non-approved substances, which means it is prohibited in sport at all times under that code.

The molecule does not correspond to the active ingredient of any UK-authorised medicine. No export restriction applies to this item; within this catalogue that restriction applies to somatropin alone.

Material supplied by NovoVita is not manufactured to medicinal standard and is not supplied for human or veterinary use.

Laboratory handling and safety

No harmonised GHS classification is assigned to MOTS-c. An absent classification is not a finding of low hazard; it reflects the fact that the substance has not been through classification. Handle it as a material of unknown toxicity.

• Personal protective equipment: nitrile gloves, safety spectacles and a laboratory coat as a minimum.
• Handling the solid: avoid generating dust when transferring lyophilised material; weigh in a controlled airflow where one is available. Allow the sealed vial to reach room temperature before opening.
• Spills: collect solid without raising dust, wipe residues with damp absorbent material, and decontaminate the surface. Do not sweep dry.
• Disposal: as chemical waste under local arrangements. Do not discharge to drain.
• Records: record the diluent, the volume added and the date on the vial when a solution is prepared. The concentration is only recoverable later if the volume was written down.

The research-use statement rendered at the foot of this page is the operative one for this material.

Related compounds and consumables

Other entries in the same catalogue category, Longevity & Cellular:

• NAD+ — identity, handling and published literature
• SS-31 — identity, handling and published literature

Diluents:

• Bacteriostatic water — composition, preservative and handling
• Sterile water — composition and handling

Tools:

• Reconstitution calculator, with this vial selected

Availability

NovoVita SKU MS20 — MOTS-c 20mg. 20 mg lyophilised solid in a sealed vial, supplied without diluent.

Price: £39.99

Quantity pricing: 3–4 8% · 5–9 12% · 10–14 18% · 15–19 20% · 20+ 22%

References and provenance

Article titles are omitted from the citation lines below where the title is itself written in claim register. Every reference is retrievable by its PMID or DOI, and the model is named in each line.

1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. Cell Metabolism. 2015;21(3):443–454. Model: cell culture and mouse, including diet-induced obesity. PMID 25738459
2. Reynolds JC, Lai RW, Woodhead JST, et al. Nature Communications. 2021;12(1):470. Model: young, middle-aged and old mice, with accompanying human exercise measurements. PMID 33473109 · doi:10.1038/s41467-020-20790-0
3. Mills AR, de Souza A, Pham T, Mugisho OO. Experimental Physiology. 2026;111(8):3742–3752. Model: rats, high-fat diet plus streptozotocin. PMID 42321010
4. Xing L, et al. Inflammation and Regeneration. 2026. Model: human mesenchymal stromal cells, in vitro. PMID 42324588
5. Santhanam SS, et al. Molecular Biology Reports. 2026;53(1):873. Model: ex vivo isolated female Wistar rat hearts (n = 6 per group). PMID 42228044
6. Horwath O, et al. Experimental Physiology. 2026;111(8):3772–3783. Model: human observational; individuals with cerebral palsy and comparison participants. PMID 42349896
7. CohBar Inc. Topline results, CB4211 Phase 1a/1b. Model: human, Phase 1; the molecule tested was CB4211, an analogue, not MOTS-c. Announcement
8. Alzheimer’s Drug Discovery Foundation, Cognitive Vitality review: MOTS-c. Secondary review of the published literature. Review (PDF)

Identity data — sequence, molecular formula, average molecular weight, CAS number and PubChem CID — are PubChem-verified. Derived figures, namely the monoisotopic mass, the charge-state m/z values and the net charge, are calculated from the stated formula and sequence and are marked as calculated where they appear.

Last reviewed 8 August 2026 — first publication of this entry.

Research use only

This material is supplied strictly for laboratory research use. It is not a medicine, it is not authorised by the MHRA or any other regulator for human or veterinary use, and it is not supplied for consumption, ingestion or administration to humans or animals. No claim is made or implied that it diagnoses, treats, cures or prevents any disease or condition. Purchasers are responsible for ensuring that they are legally permitted to obtain and handle this material.