MOTS-c

What MOTS-c is

MOTS-c is a 16-amino-acid peptide whose genetic code sits in the mitochondria's own DNA rather than in the cell nucleus. The name stands for "mitochondrial open reading frame of the 12S rRNA type-c": the short stretch of code that makes it lies inside the mitochondrial gene for 12S ribosomal RNA. A University of Southern California team led by Changhan Lee and Pinchas Cohen described it in Cell Metabolism in 2015.

In that paper's cell and mouse experiments, the peptide's main target appeared to be skeletal muscle. Inside cells it slowed the folate cycle and the purine production tied to it, which in turn switched on AMPK, an energy sensor that exercise also activates. That AMPK link is why MOTS-c gets called an "exercise mimetic" in forums and vendor copy.

Most of the foundational work comes from one group. Cohen founded CohBar, the company that later developed a MOTS-c analog, and a 2020 paper lists both Cohen and Lee as CohBar consultants and shareholders. Independent replication matters more than usual here.

How this section is organized

This page is the overview for MOTS-c within the mitochondrial peptides category, which also covers SS-31. The pages below go deeper.

• How MOTS-c affects glucose and fat metabolism covers the AMPK mechanism and the insulin-sensitivity findings in mice.
• MOTS-c as an exercise mimetic looks at the claim that the peptide reproduces some cellular effects of training, and where the comparison breaks down.
• MOTS-c for endurance and performance is written for athletes and lifters, with the mouse treadmill data and what users say about endurance.

What the mouse studies found

Metabolism

In the 2015 study, MOTS-c treatment prevented insulin resistance in mice, both the age-related kind and the kind caused by a high-fat diet, and it prevented diet-induced obesity. The mice got the peptide by injection into the abdominal cavity (intraperitoneal), a route people don't use, so the exposure isn't comparable to a subcutaneous shot.

Exercise and aging

A 2021 Nature Communications study from the same group gave mice daily intraperitoneal MOTS-c. Young mice on a high-fat diet ran longer on a treadmill at 15 mg/kg a day, and so did middle-aged (12-month) and old (22-month) mice after two weeks at that dose. Mice started at about 24 months on 15 mg/kg three times a week later scored better on physical tests such as grip strength. Median lifespan trended about 6% longer, but the survival curve wasn't significantly different (P = 0.23). No published source has converted these mouse doses to a human dose, and we don't either.

What has been measured in people

As of October 2026, every published human MOTS-c study we found measured the body's own (endogenous) peptide. None gave MOTS-c to anyone.

The exercise data come from the 2021 paper. Ten sedentary young men rode a stationary bike, and MOTS-c in their thigh muscle rose about 11.9-fold after exercise compared with each man's starting level. Blood levels rose about 1.5-fold during and after the ride and were back to baseline four hours later. That shows exercise raises MOTS-c. It doesn't show that injecting it reproduces exercise.

The aging data are less tidy than the "MOTS-c declines with age" line suggests. A 2020 study of healthy men found blood levels were lower in older men, while muscle levels in middle-aged (45-55) and older (70-81) men were about 1.5 times higher than in young men (18-30). Blood and muscle moved in opposite directions, so a blood test may say little about muscle.

The obesity data conflict. A 2018 study of 20 adults found similar blood levels in lean and obese people, while a Chinese study the same year found lower levels in obese boys. A 2026 Mayo Clinic study found the opposite in adults: higher levels with obesity, unchanged six months after bariatric surgery. A 2024 meta-analysis of seven studies (602 participants) found levels lower in type 2 diabetes but higher in obesity. Reported concentrations also differ by more than a thousandfold between labs (hundreds of pg/mL in one, hundreds of ng/mL in another), which points to assay problems as much as biology.

CB4211, the analog that was dropped

The closest thing to human dosing data comes from CB4211, a modified version of MOTS-c developed by CohBar. After a one-week dose-escalation stage in 65 healthy adults, the Phase 1b stage gave 25 mg by subcutaneous injection once daily for four weeks to 20 adults with obesity and fatty liver (11 on CB4211, 9 on placebo).

According to the company's 2021 topline release, the liver enzyme ALT fell 21% on CB4211 while rising 4% on placebo, and AST fell 28% vs. 11%. Liver fat dropped about 5 percentage points in both groups, so CB4211 did no better than placebo there. The only side effect seen in more than 10% of CB4211 recipients was a transient, mostly mild-to-moderate injection-site reaction.

Injection-site reactions shaped the program. CohBar's SEC filings say it paused the trial in November 2018 to address them, and in 2023 the company said the trial formulation wasn't suitable for further development. In November 2023, after a planned merger fell through, CohBar announced it would liquidate and dissolve. As of October 2026, nobody is developing CB4211.

One registry entry claims to test native MOTS-c: MOTS-MET (NCT07505745), a Phase 2a trial listing 120 adults with prediabetes and once-daily subcutaneous dosing for 12 weeks, with no dose stated. Curo, a vendor that sells MOTS-c, reports that the same sponsor filed near-identical records for other peptides, one of which describes itself as fictional. We don't treat MOTS-MET as evidence that anyone is giving MOTS-c to people.

Legal and sport status

As of October 2026, MOTS-c isn't FDA-approved for any use. In the US it's sold as a research-use-only chemical, a label that doesn't make it a medicine. In April 2026 the FDA removed it from Category 2 of its interim compounding list after its nomination was withdrawn, which didn't make it eligible for pharmacy compounding. In July 2026 the FDA's Pharmacy Compounding Advisory Committee voted 7-5, with 2 abstentions, to recommend adding it to the 503A bulks list. That vote is advisory; the FDA would still need formal rulemaking, and as of October 2026 none has started.

WADA's 2026 Prohibited List names MOTS-c under S4.4.1 (AMPK activators) and bans it at all times, in and out of competition. S4.4 substances are non-Specified, meaning WADA doesn't treat them as likely to have been taken for a reason other than performance. Our page on legal and ethical considerations for athletes covers what that means in practice.

What users report

The doses in circulation come from forums, not trials. Users commonly describe 5 mg by subcutaneous injection two or three times a week, which lines up with the 10-15 mg a week range in our peptide entry. Reported doses run from about 1 mg three times weekly up to 5-10 mg daily for short blocks. Some time a dose before training; no study has tested that.

The most common complaint in user reports is injection-site reactions, often itchy welts or hard lumps that can last for days. That matches the CB4211 trial and CohBar's own trouble, one of the few places where users and trial data agree. A few secondhand forum reports describe tongue or throat swelling; we couldn't verify them. Reports on effects are split: some users describe better endurance, others notice nothing. Product quality is one likely reason, since no regulator checks gray-market vials, and expectation effects are another.

What we still don't know

The central question is still open: nobody has published what happens when people inject native MOTS-c. There are no human data on how long it lasts in the blood or whether any dose changes insulin sensitivity or endurance. If MOTS-MET is a real trial, its results would be the first.

Until labs agree on how to measure MOTS-c, it's hard to say whether levels really fall with age or rise with obesity. Long-term safety is unknown, since the longest controlled human exposure is four weeks of a different molecule; our page on long-term health implications covers that question for mitochondrial peptides generally. On the regulatory side, watch whether the FDA acts on the July 2026 advisory vote.