Mitochondrial-Derived Peptide for Metabolic Homeostasis & Longevity
MOTS-c — Mitochondrial Open Reading Frame of the 12S rRNA-c
Last reviewed: August 2026
MOTS-c is a peptide encoded in mitochondrial DNA that acts as a metabolic master regulator, activating AMPK to improve insulin sensitivity, increase fat burning, and promote longevity pathways. It was discovered in 2015 and found at higher levels in centenarians.
MOTS-c activates AMPK in muscle and liver, producing effects similar to intense exercise: increased glucose uptake, enhanced fat oxidation, and improved insulin sensitivity.
MOTS-c levels decline with age and obesity. Its discovery in centenarians at higher levels than in younger adults suggests it may be a key mediator of exceptional longevity.
MOTS-c is a mitochondrial-derived peptide that activates AMPK to mimic the metabolic effects of exercise, with declining levels linked to aging and metabolic disease.
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial genome — one of the only peptides known to be encoded by mitochondrial DNA. It regulates metabolic homeostasis, insulin sensitivity, and exercise capacity by activating AMPK signaling. Circulating MOTS-c levels decline with age, and higher levels have been found in centenarians.
MOTS-c is a 16-amino-acid peptide (MRWQEMGYIFYPRKLR) encoded within the 12S rRNA gene of the mitochondrial genome. Unlike nuclear-encoded peptides, MOTS-c is translated in the mitochondrial matrix and can translocate to the nucleus under metabolic stress, directly regulating gene expression.
MOTS-c mimics the metabolic effects of exercise by activating AMPK in skeletal muscle and liver, increasing glucose uptake and fatty acid oxidation.
MOTS-c activates AMP-activated protein kinase (AMPK) in skeletal muscle and liver, mimicking the metabolic effects of exercise and caloric restriction. It also regulates the folate cycle and one-carbon metabolism, affecting nucleotide synthesis, methylation reactions, and redox balance. Under metabolic stress, MOTS-c translocates to the nucleus where it regulates stress-response genes.
Activates AMP-activated protein kinase (AMPK) in skeletal muscle and liver, mimicking the metabolic effects of exercise and caloric restriction.
Regulates the folate cycle and one-carbon metabolism, affecting nucleotide synthesis, methylation reactions, and redox balance.
Improves insulin sensitivity in skeletal muscle by activating AMPK-dependent glucose transporter (GLUT4) translocation, independent of insulin signaling.
Each outcome rated by the highest level of evidence available. Tiers follow our 5-tier methodology.
Study counts reflect peer-reviewed publications in the evidence database below. "Theoretical" outcomes have mechanistic rationale only. Learn about our evidence tiers →
1 cited study — model, sample size, outcome, and effect size from published literature.
| Study | Model | Sample | Outcome | Effect Size | Level |
|---|---|---|---|---|---|
Lee C, et al. (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and redu… PubMed | Rodent (mouse) — diet-induced obesity | n=40 | Reduced body weight, improved insulin sensitivity, and AMPK activation | Body weight reduction: ~15% vs. control; insulin sensitivity: ~2× improvement | Animal |
MOTS-c — half-life, bioavailability, onset, and duration data
| Parameter | Value | Source |
|---|---|---|
| Half-Life (t½) | ~1–2 hours (estimated) Preclinical data; no human PK studies | Preclinical Data |
| Time to Peak (Tmax) | ~30–60 minutes Preclinical estimates | Preclinical Data |
| Bioavailability (F) | Estimated 60–80% (SC/IM) No published human bioavailability data | Preclinical Data |
| Onset of Action | Hours to days AMPK activation and metabolic effects | — |
| Duration of Action | Variable Metabolic effects persist beyond plasma half-life | — |
Mitochondria-derived peptide encoded in the 12S rRNA gene. Activates AMPK and improves insulin sensitivity. Endogenous levels decline with age. Research-stage only; no clinical trials completed.
References:
• Lee C et al. Cell Metab 2015
• Kim KH et al. Nat Commun 2018
Peer-reviewed literature supporting the research profile of MOTS-c
The following peer-reviewed studies form the primary evidence base for MOTS-c's research profile. All references are sourced from PubMed, NCBI, and peer-reviewed scientific journals. Published research is available through PubMed, NCBI, and peer-reviewed biomedical journals.
Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015.PMID: 25738459
MOTS-c reduced obesity and improved insulin sensitivity in diet-induced obese mice via AMPK activation.
Kim SJ, et al. Mitochondrially derived peptides as novel regulators of metabolism. Journal of Physiology. 2017.PMID: 28574175
Review of MOTS-c and other mitochondrial-derived peptides as metabolic regulators.
Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021.PMID: 33473109
MOTS-c levels increase with exercise and decline with age; supplementation improved physical performance in aged mice.
Longevity Research
Purgo Labs list price, read 12 Sep 2026 · per-lot COA on the vendor page
10mg $49.99 → $39.99 with code HEALTH (20% off; price read 1 Nov 2026)
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5 documented interactions for MOTS-c
Both target cellular aging pathways via different mechanisms — Epithalon via telomerase, MOTS-c via AMPK/mitochondrial function.
Interaction data is based on published research, known pharmacological mechanisms, and clinical practitioner experience. Evidence tiers: Clinical = human data; Emerging = preclinical/case reports; Theoretical = mechanism-based inference. Always consult a qualified healthcare provider before combining compounds.
Source MOTS-c at Purgo Labs
10mg $49.99 list · $39.99 with code HEALTH · lab-verifiable COA per lot
Animal and cell data only for MOTS-c itself; a company-reported Phase 1 of an analogue (CB4211) is the nearest human data
MOTS-c is a mitochondrial-encoded peptide identified in 2015 that improves metabolic markers and exercise capacity in mice through AMPK signalling. No controlled human trial of MOTS-c has been published. The closest human data are from CohBar's 2020–2021 Phase 1a/1b of CB4211, a modified analogue, which the company described as well tolerated with injection-site reactions; that description was a press release, not a paper.
Research-use information only. Research-grade MOTS-c is not an approved medicine; where trial or label figures appear below they belong to the pharmaceutical product studied, not to any research vial. This section does not give dosing or medical advice.
Every rate carries its source. Where no source exists, no rate is printed.
| Effect | Rate (sourced) | Detail | Source |
|---|---|---|---|
| Injection-site reactions | not quantified | Reported by the developer as the main adverse event in the CB4211 (analogue) Phase 1; unquantified in any publication. | CohBar company statements 2021 (not peer-reviewed) |
| Adverse effects in animal studies | not quantified | Not reported as a specific finding in the primary mouse studies; the studies were not designed as toxicology. | Lee et al. 2015; Reynolds et al. 2021 |
Regulatory status: Not approved anywhere; MOTS-c is on the WADA prohibited list (S4.4 metabolic modulators).
Everything above describes MOTS-c the molecule. The risk specific to a research vial is different: it may not contain MOTS-c at the labelled amount, and it may contain what the synthesis left behind. Identity (mass spectrometry), purity (HPLC), measured net content and an endotoxin result are the four lines on a certificate that bear on adverse effects, and only a certificate you can check at the laboratory tells you any of them. This is what we have verified for MOTS-c so far.
43 of the 105 vendors on our scoreboard list MOTS-c with a price we read on the product page (11 Sep 2026–1 Nov 2026). Of those, 39 name their testing laboratory, 32 publish certificates that resolve on the lab's own site, and 37 publish measured milligrams against the label. The full ranking, with every dated price, is on Best MOTS-c Vendors.
| Vendor | Rubric | Lab named | Price read |
|---|---|---|---|
| MyPurePeptidepartner | 10/10 | Janoshik Analytical | $45.00 · 40mg · 1 Nov 2026 |
| Oneday Compoundspartner | 10/10 | ILS Laboratories (San Diego, CA) | $26.99 · 10mg · 29 Oct 2026 |
| Panda Peptides | 10/10 | Janoshik Analytical · ILS Labs (per batch) | $39.99 · 10mg · 25 Oct 2026 |
| Premier Bio Labs | 10/10 | ILS Laboratories + Freedom Diagnostics | $39.00 · 10mg · 1 Nov 2026 |
| Purgo Labspartner | 10/10 | SteriGenix · Freedom Diagnostics | $49.99 · 10mg · 1 Nov 2026 |
Top 5 by rubric score; 38 more on the ranking page.
None yet for MOTS-c specifically. The COA library holds the certificates we have read for each vendor on other compounds, which is the next best signal of how that vendor documents a lot.
Not in a published controlled trial. A modified analogue (CB4211) went through Phase 1 in 2020–2021; the developer reported it as well tolerated with injection-site reactions, but no paper followed and the programme was later discontinued.
Side-effect section last reviewed 2026-09-13. Moved from the standalone side-effects page on 10 October 2026; text unchanged.
MOTS-c is legal to purchase and possess in the United States as a research chemical. It is a mitochondria-derived peptide that is not a controlled substance under the DEA Controlled Substances Act, and it is not FDA-approved for human use.
| Jurisdiction | Status as stated |
|---|---|
| United States | Not a controlled substance. Legal to purchase as a research chemical. Not FDA-approved for human use. |
| Canada | Not a scheduled substance. Legal for research purposes. Not approved by Health Canada for human use. |
| United Kingdom | Not a controlled drug under the Misuse of Drugs Act. Legal for research purposes. |
| Australia | Not listed as a scheduled substance by the TGA. Legal for research purposes. |
| European Union | Not a controlled substance in most EU member states. Legal for research purposes. |
| WADA / Sports | MOTS-c is not explicitly listed on the WADA Prohibited List, but as a peptide with metabolic effects it may fall under S4 (Hormone and Metabolic Modulators). Athletes should consult their governing body. |
Statements above are as our legal-status page for MOTS-c stated them in 2025; they were moved here on 10 October 2026 and were not re-verified in the move. Regulations change. This is general information, not legal advice; check the current position with your own jurisdiction's regulator before relying on it.
No. MOTS-c is not listed as a controlled substance under the US DEA Controlled Substances Act. It is not scheduled at the federal level in the United States.
Yes. MOTS-c can be legally purchased as a research chemical in the United States. It should not be sold or purchased for human consumption.
No. MOTS-c is not FDA-approved for any human use. It is an emerging research peptide with ongoing studies in metabolic and longevity research.
MOTS-c may fall under WADA's S4 category (Hormone and Metabolic Modulators) due to its metabolic effects. Athletes subject to anti-doping rules should consult their governing body before use.
MOTS-c is not a scheduled substance in Canada. It is legal for research purposes but is not approved by Health Canada for human use.
MOTS-c is a mitochondrial-derived peptide with interesting metabolic biology, but human efficacy data does not exist yet. The foundational work is in mice and cell systems. Present as an early-stage research compound, not a proven metabolic therapy.
Purgo Labs offers MOTS-c with ≥99% purity, third-party certificates of analysis, and fast FedEx shipping. This is an affiliate link — we may earn a commission at no cost to you.
