MOTS-c: what the published research covers

PlatinumLongevity.co sells MOTS-c for laboratory research use only. This page summarizes the published literature. It is not guidance for human use.

What it is

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. It is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial 12S rRNA gene. A University of Southern California group reported it in 2015 (Lee et al., 2015).

The human sequence is MRWQEMGYIFYPRKLR. PubChem lists the formula C101H152N28O22S2, a molecular weight of 2174.6 g/mol, and CAS number 1627580-64-6 (PubChem). Salt forms weigh more. Cayman Chemical lists 2288.6 for its trifluoroacetate salt (Cayman Chemical).

What has been studied

Most MOTS-c data come from cells and mice. Human data so far measure the body's own MOTS-c. No published study giving MOTS-c to people was found for this review.

Metabolism in mice

The 2015 paper used human and rat cell lines and male mice. In mice, MOTS-c prevented insulin resistance linked to age and to a high-fat diet. It also prevented diet-induced obesity. The authors reported that it acts on the folate pathway and purine synthesis, which leads to AMPK activation. They named skeletal myocytes as its main target (Lee et al., 2015). Group sizes in the main mouse experiments ranged from 6 to 10.

Physical capacity in aged mice

A 2021 study gave MOTS-c to young, middle-aged, and old mice. It reported better physical performance in all three age groups. Starting the peptide late in life raised physical capacity in old mice. The same paper reported that exercise raised the body's own MOTS-c in human skeletal tissue and blood (Reynolds et al., 2021).

Human exercise studies

A 2021 study randomized 30 people to endurance exercise, resistance exercise, or rest, with 10 per group. MOTS-c in plasma showed only a trend toward a rise after endurance exercise. Plasma levels did not track fitness measures (von Walden et al., 2021). No one in this study received MOTS-c.

Host defense

A 2026 paper reported that MOTS-c acts against E. coli and MRSA in vitro. In a mouse model of acute peritonitis, it neutralized MRSA infectivity. Human monocytes made more of their own MOTS-c in response to immune signals (Rice et al., 2026).

Regulatory status in the US, October 2026

• FDA lists MOTS-c among substances whose nominations were withdrawn. FDA says it has not identified any human exposure data on drug products containing MOTS-c. It also cites a possible immunogenicity risk (FDA).
• On April 15, 2026, FDA announced it would remove MOTS-c and 11 other peptides from Category 2. Removal does not make them eligible for 503A compounding (Frier Levitt, April 2026).
• FDA presented MOTS-c to its Pharmacy Compounding Advisory Committee on July 23, 2026 (FDA briefing).
• The committee voted 7 yes, 5 no, 2 abstain to recommend it for the 503A bulks list. FDA scientists had recommended against it (McDermott, July 2026).
• The vote is advisory. As of September 17, 2026, FDA still had to complete formal rulemaking (Frier Levitt, September 2026).

On August 24, 2026, FDA sent warning letters to sellers of "research use only" peptides. In one letter, FDA said website evidence showed the products were intended for human use, despite the labels (FDA warning letter). That letter did not name MOTS-c.

What is unknown or contested

• Human effects of the peptide. FDA reports no human exposure data on MOTS-c drug products. Effects seen in mice have not been tested in people in any published trial found here.
• Human safety. FDA says it lacks important information on whether MOTS-c would cause harm in humans.
• Endogenous levels. The human exercise study found only a trend in plasma MOTS-c. How the body's own levels relate to fitness is not settled.
• Source concentration. Three of the studies cited here share one author, Changhan Lee, of the University of Southern California.
• Mechanism. Proposed mechanisms now span metabolism, gene regulation, and immune defense. How these fit together is still open.

Handling notes for a lab

Cayman Chemical supplies MOTS-c (human) as a trifluoroacetate salt in solid form. It lists storage at -20°C and states the product is not for human or veterinary use (Cayman Chemical). Note the salt form when you calculate concentrations. Follow the certificate of analysis for your lot.

Lot documentation and specifications are on the product page, MOTS-c at PlatinumLongevity.co.