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Research review · Sources checked October 16, 2026

MOTS-c: what the research shows

MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial 12S rRNA gene. It is not an FDA-approved drug, and FDA reports no human exposure data for it by any route.[1][3][4]

What MOTS-c is

MOTS-c was described in 2015 as a mitochondrial-derived peptide that acts mainly in skeletal muscle, inhibiting the folate cycle and activating AMPK. In male mice on a high-fat diet, 0.5 mg/kg a day by injection for eight weeks prevented obesity without changing food intake.[1] In 2021 the same group reported that exercise raised MOTS-c in human muscle and blood, and that 15 mg/kg improved running in mice; a late-life treatment showed only a non-significant lifespan trend (P = 0.23).[2]

Regulatory status

FDA lists MOTS-c among substances previously placed in category 2 of its compounding interim policies whose nominations were withdrawn, stating it “has not identified any human exposure data” for products containing it.[4] FDA’s 2026 review found no in-vivo pharmacokinetic or toxicity studies and recommended against adding it to the compounding list.[3] In July 2026 the advisory committee voted 7 to 5, with 2 abstentions, in favor.[8] MOTS-c is on the World Anti-Doping Agency’s 2026 prohibited list.[9]

Human data

Published human studies measure the body’s own MOTS-c; none we found gave MOTS-c to people.[7] The gene variant m.1382A>C (K14Q) was linked to more type 2 diabetes in less active Japanese men and not to exceptional longevity.[5] CohBar’s modified analog CB4211 lowered liver enzymes over four weeks in 20 people with fatty liver, but liver fat fell similarly on placebo and injection-site reactions were common (79% vs 33%).[6]

What is not known

There are no published human trials of MOTS-c itself, no human pharmacokinetic data, and no established human dose. In human blood in a test tube it is quickly cut into shorter fragments.[3] For the full paper trail, see our teardown below.

References

  1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. doi:10.1016/j.cmet.2015.02.009. PMID 25738459; full text PMC4350682. Conflict statement: one author a CohBar stockholder and consultant, another a consultant. https://pubmed.ncbi.nlm.nih.gov/25738459/. Checked October 16, 2026.
  2. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12:470. doi:10.1038/s41467-020-20790-0. PMID 33473109; full text PMC7817689 (lifespan: “trend towards increased median (6.4%) and maximum (7.0%) lifespan,” overall P = 0.23). Two authors disclosed they are CohBar consultants and shareholders. https://pubmed.ncbi.nlm.nih.gov/33473109/. Checked October 16, 2026.
  3. U.S. Food and Drug Administration. Pharmacy Compounding Advisory Committee briefing document: MOTS-c-related bulk drug substances (MOTS-c free base and MOTS-c acetate). Review memo dated May 11, 2026, for the July 23–24, 2026 meeting. Sections on nomination (Wells Pharmacy Network, later withdrawn), characterization, pharmacokinetics, nonclinical toxicity, human data, FAERS, immunogenicity and FDA’s recommendation. https://www.fda.gov/media/193347/download. Checked October 16, 2026.
  4. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (Category 2). Content current as of April 22, 2026. MOTs-C appears in the table of substances nominated but withdrawn: “FDA has not identified any human exposure data on drug products containing MOTs-C administered via any route.” https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks. Checked October 16, 2026.
  5. Zempo H, Kim SJ, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1692-1717. doi:10.18632/aging.202529. PMID 33468709; full text PMC7880332 (m.1382A>C, K14Q; three cohorts, 27,527 people; 736 centenarians, 7.7% vs 7.5%; “m.1382A>C polymorphism is unlikely to be involved with exceptional longevity”). One author disclosed CohBar consulting and stock. https://pubmed.ncbi.nlm.nih.gov/33468709/. Checked October 16, 2026.
  6. CohBar, Inc. Q2 investor presentation, August 10, 2021, filed as Exhibit 99.3 to an SEC Form 8-K (Phase 1b n = 11 CB4211 vs 9 placebo; ALT −21% vs +4%, AST −28% vs −11%, glucose −6% vs 0%; absolute liver fat −5.03 vs −4.88 points, “liver fat content was also reduced in placebo arm”; injection site reactions 79% vs 33%; no serious adverse events). https://www.sec.gov/Archives/edgar/data/1522602/000121390021041377/ea145151ex99-3_cohbar.htm. Checked October 16, 2026.
  7. Jabbit count of PubMed records, October 16, 2026, query MOTS-c[tiab] OR “MOTS c”[tiab] OR MOTSc[tiab] OR “mitochondrial open reading frame of the 12S rRNA”[tiab] via NCBI E-utilities: 264 records; our classification of each, with method: https://jabbitapp.com/research/sources/motsc-pubmed-2026-10-16.json.
  8. MDside. The FDA advisory vote on six peptides: what has to happen before a clinic can use them. October 9, 2026 (MOTS-c vote 7 yes, 5 no, 2 abstain). https://www.mdside.com/peptide-advisory-vote-what-happens-next/. Holland & Knight, Peptides at a Crossroads, October 2026: https://www.hklaw.com/en/insights/publications/2026/10/peptides-at-a-crossroads-what-wellness-providers-need-to-know. Checked October 16, 2026.
  9. World Anti-Doping Agency. The 2026 Prohibited List, S4.4.1 (activators of AMP-activated protein kinase, including “mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)”), in force January 1, 2026. https://www.wada-ama.org/en/resources/world-anti-doping-code-and-international-standards/prohibited-list. Checked October 16, 2026.

This page summarizes published research and regulatory documents. It is not medical advice and does not recommend using, sourcing, or dosing any of these substances.