Who discovered MOTS-c, and when?

Changhan Lee, Pinchas Cohen, and colleagues at USC's Leonard Davis School of Gerontology reported MOTS-c in Cell Metabolism on March 3, 2015. Lee was the first author and Cohen the senior author. Researchers from UCLA and the National Institutes of Health also contributed to the work.

Is MOTS-c the same peptide as humanin?

MOTS-c and humanin are different peptides, meaning short chains of protein building blocks. Humanin was reported by Hashimoto, Nishimoto, and colleagues in 2001. Its discovery helped establish the idea that mitochondrial genetic material might contain instructions for other small signals, which motivated the later search that identified MOTS-c.

Did the 2021 exercise study give people MOTS-c?

The human part of the 2021 Reynolds study did not administer MOTS-c. Researchers measured naturally occurring levels in blood and muscle around a cycling session in 10 healthy young men. Treatment experiments in the same paper involved mice. Those are different kinds of evidence, even though they appear together.

Is CB4211 the same thing as MOTS-c?

CB4211 is a modified relative of MOTS-c, rather than the unchanged peptide. CohBar announced first human dosing of CB4211 in July 2018. Findings from that development program concern its particular molecule and study design; they cannot automatically establish the effects or safety of a compounded MOTS-c formulation.

Does finding MOTS-c in the body establish that an injection is safe?

Finding a peptide in the body does not establish the safety of administering it as a medication. Treatment changes the amount and pattern of exposure, and a manufactured formulation needs its own evaluation. The discovery and exercise papers answer biological questions; they do not establish long-term safety for prescribed MOTS-c.

Who Discovered MOTS-c? The 2015 USC Discovery

The scientists who discovered MOTS-c were Changhan Lee, Pinchas Cohen, and colleagues at the University of Southern California's Leonard Davis School of Gerontology. They reported it in March 2015. MOTS-c is a peptide, a short chain of protein building blocks, whose instructions sit in mitochondrial DNA—the genetic material inside the cell's energy-making parts.

Who discovered MOTS-c, and what were they looking for?

Lee was the first author and Cohen the senior author of the discovery paper in Cell Metabolism, published March 3, 2015. The collaboration included researchers at UCLA and the National Institutes of Health. USC's announcement, dated March 2, identifies the team and explains why this tiny molecule drew attention.

The question was whether mitochondria could carry instructions for more small signals than scientists had recognized. An earlier discovery had opened that door.

In 2001, Hashimoto, Nishimoto, and colleagues at Keio University in Japan reported humanin. Their search concerned substances that might keep nerve cells alive under conditions related to Alzheimer's disease. The experiments were in cells; finding humanin wasn't evidence of a treatment for people with Alzheimer's. Their original PNAS paper records that earlier starting point.

Humanin helped prompt Lee and colleagues to search mitochondrial genetic sequences for another overlooked peptide. Their computer search identified the sequence that became MOTS-c.

Where does MOTS-c come from, and what does its name mean?

The name describes its genetic address. The 2015 discovery paper explains the letters this way:

Part	Plain meaning
M	Mitochondrial: referring to the cell's energy-making structures.
O	Open reading frame: a stretch of genetic instructions that can spell out a peptide.
T and S	Twelve S, or 12S: the named ribosomal RNA gene containing those instructions. Ribosomal RNA helps form the cell's protein-making machinery.
c	The authors' type-c designation.

The resulting peptide has 16 amino acids, the building blocks of proteins. Its genetic origin doesn't establish what a manufactured vial will do in a person. That takes separate testing.

What the first paper actually showed

The researchers connected MOTS-c with AMPK, a cell's energy-sensing switch. Their cell experiments linked this response to changes in the folate and methionine cycles—linked chemical reactions involving vitamin B9 and the amino acid methionine.

In mice, the team studied insulin sensitivity—how readily tissues respond to the hormone that helps control blood sugar. They reported less weight gain and less insulin resistance in treated animals eating a high-fat diet. USC's account of the experiments also makes clear that the treatment findings came from mice.

That established a reason to investigate. It didn't establish a human weight-loss dose, long-term safety, or a substitute for exercise. The broader evidence belongs in our MOTS-c benefits article.

The first human data: measurements before treatment

Human observations started earlier than the often-cited 2021 exercise paper. The 2015 paper already reported detecting MOTS-c in human blood samples. Detection answers whether a signal is present; it doesn't answer whether injecting more helps.

In January 2021, Joseph Reynolds and colleagues published an exercise study in Nature Communications. Ten healthy, sedentary young men cycled while researchers measured MOTS-c in blood and muscle. Levels rose around exercise. The human experiment involved no MOTS-c treatment; the paper's injection experiments were in mice.

Another January 2021 paper, led by Hirofumi Zempo, examined a genetic variant—a change in a DNA instruction—called m.1382A>C. That means an A was replaced by a C at position 1382 in mitochondrial DNA, changing the peptide's sequence.

Across three study groups totaling 27,527 people, the variant was associated with diabetes in men, but not women. In the Japanese J-MICC group, the association was strongest among the least active men. The Aging paper describes an association, not proof that MOTS-c treatment prevents diabetes.

Those distinctions matter when reading about MOTS-c for weight loss or peptides for insulin resistance.

Why SS-31 has a different origin story

SS-31 also appears in discussions of mitochondria, but it comes from a different line of work. Researchers including Hazel Szeto and Peter Schiller developed peptides designed to reach the inner mitochondrial membrane, the structure's inner boundary. Their 2004 paper describes that approach.

MOTS-c was identified through genetic instructions already present in the body. SS-31 belongs to a designed peptide family. Sharing an interest in mitochondria doesn't make them interchangeable or establish a reason to combine them.

From the lab to drug development and online vials

USC reported in 2015 that intellectual property from the work had been licensed to a biotechnology company. By July 12, 2018, CohBar was announcing first human dosing of CB4211, an analog—a modified relative—of MOTS-c. The company's announcement concerns that specific drug candidate.

Meanwhile, MOTS-c itself appeared in online peptide catalogs. FDA's history of its use documents online marketing but says the extent of historical compounding is unknown. That leaves no reliable date for a first gray-market sale, meaning a sale without a prescription. A discovery paper, a company trial, and an online vial are separate parts of this history.

What changed in 2026?

As of September 10, 2026, the day this article was written, a recent publication has extended the story beyond metabolism. Michelle Rice, Changhan Lee, and colleagues published the final journal version of an eLife study on August 18, updated August 26, examining MOTS-c in immune defense. Earlier reviewed versions appeared in 2023 and 2025. The work used bacteria, cultured cells, and mice; it wasn't a treatment trial in patients with infections.

As of September 10, 2026, the day this article was written, the MOTS-MET registry record, last updated April 1, lists a planned 120-person treatment study with no results posted. Hudson Biotech sponsors this study; the record marks it as not studying a U.S. FDA-regulated drug product. Registration describes a planned test, not its results or a drug authorization.

Where MOTS-c stands with FDA today

As of September 10, 2026, the day this article was written, FDA's nominations PDF, marked “Updated May 14, 2026,” does not list MOTS-c in Categories 1–3. But FDA's May 11 briefing memo says it received a nomination, the nomination was withdrawn, and FDA continued reviewing MOTS-c on its own initiative. The July 23–24 meeting materials concern the 503A bulks list, a list of ingredients evaluated for use in certain compounded prescriptions; our FDA peptide decision article covers the wider committee process. MOTS-c is not FDA-approved, and the compounded formulation offered here is not FDA-approved.

A licensed provider may still prescribe a compounded formulation where applicable rules permit; that decision is between the patient and the doctor.

The prescription route starts with a person

At Promise, a licensed provider reviews every request, and not everyone qualifies. The conversation covers medical history, current medicines, what someone hopes to address, and the limits of the evidence. If prescribed, the formulation comes through a licensed U.S. compounding pharmacy.

The discovery explains why MOTS-c is being studied. A prescribing decision still needs to account for the individual sitting across the table.