What is MOTS-c studied for? What published studies have found

What is MOTS-c studied for in research?

MOTS-c is studied in laboratory research as a subject for understanding how mitochondria signal to the rest of the cell. Since Lee et al. described it in Cell Metabolism in 2015, groups have examined it in cultured cells and rodents for effects on glucose handling, fat accumulation, muscle performance, inflammation and organ injury, and those are animal and cell results. The FDA states that MOTS-c is not a component of any FDA-approved drug (FDA briefing document, 11 May 2026), and USADA calls it an experimental peptide being explored for therapeutic purposes (USADA, page read 14 October 2026). Every finding below is a report of what a study found.

MOTS-c studies fall into three kinds. Cell experiments ask where MOTS-c goes and which genes respond, as in Kim et al. (Cell Metabolism, 2018). Mouse experiments ask what happens to blood sugar, body composition and running ability, as in Lee et al. (2015) and Reynolds et al. (Nature Communications, 2021). Human studies mostly measure the body's own MOTS-c in blood, for example after exercise (von Walden et al., Journal of Applied Physiology, 2021). Keeping the three apart is the key to reading any headline about MOTS-c.

The same short molecule appears in several places on this site. The MOTS-c research guide walks through the first papers in plain English, and MOTS-c in Perth covers its genetic address and its classification records. This page asks a different question: what did the studies find?

Evidence limits

What has research not shown about MOTS-c?

Even the blood level of MOTS-c is hard to pin down. In a reference group of 20 healthy people, a sports-testing laboratory found that an antibody test (ELISA) reported plasma MOTS-c of 45.9 to 218.5 ng/mL and a mass-spectrometry method could not confirm those values, a two-assay comparison from one laboratory (Knoop et al., Rapid Communications in Mass Spectrometry, 2019). Studies that compare blood levels between groups therefore depend on which test each one used.

Findings from mice also travel unevenly. In one mouse study, high-fat-fed male mice treated with MOTS-c showed reduced weight and improved glucose tolerance while female mice were unaffected, a mouse result that does not establish effects in people (Zempo et al., Aging, 2021).

Research reference material is a separate matter from the molecules in these papers. The site catalogue lists MOTS-C reference material for laboratory work, and how to read a certificate of analysis explains what that paperwork can and cannot show about a batch.

What have studies of MOTS-c found?

Studies of MOTS-c report results in three settings. In cultured cells, MOTS-c activated AMPK (an energy-sensing enzyme), not evidence of the same effect in people (Lee et al., Cell Metabolism, 2015), and it moved into the nucleus under glucose restriction, again not evidence of the same effect in people (Kim et al., Cell Metabolism, 2018). In mice, MOTS-c treatment prevented diet-induced obesity and insulin resistance, a mouse result that does not establish effects in people (Lee et al., 2015). In young, middle-aged and old mice, MOTS-c treatment raised physical performance, not evidence of the same effect in people (Reynolds et al., Nature Communications, 2021). In 10 sedentary young men, exercise raised the body's own MOTS-c about 11.9-fold in muscle and about 1.6-fold in blood, a measurement of the natural peptide in one small group and not of MOTS-c given to anyone (Reynolds et al., 2021). No completed study of MOTS-c given to people for these outcomes was found in the sources searched.

The table below lines up eight studies by setting, so the model sits beside each result. The right-hand column records what each design cannot show.

In cell lines under glucose restriction, MOTS-c moved into the nucleus and changed the activity of stress-response genes, including those with antioxidant response elements regulated by transcription factors such as NRF2, a master switch for antioxidant defences, a cell-culture result with no animal or human outcome (Kim et al., Cell Metabolism, 2018). In cell-free tests and in mouse muscle, MOTS-c bound and activated the enzyme CK2, a proposed mechanism in laboratory and mouse models that does not establish the same action in people (Kumagai et al., iScience, 2024).

Your own body makes MOTS-c, and the most human result in this literature is that exercise pushed the body's own level up, in muscle and in blood, in 10 sedentary young men, a small endogenous-peptide study that did not test supplied MOTS-c (Reynolds et al., Nature Communications, 2021). A report of laboratory-made MOTS-c doing the same in a person was not found in the sources searched.

What does research show MOTS-c does in the body?

In cells and mice, Lee et al. found that MOTS-c inhibits the folate pathway and the purine (DNA building-block) production tied to it, which leads to AMPK activation, with skeletal muscle as its apparent primary target organ in mice, a laboratory and mouse result which does not establish the same action in people (Cell Metabolism, 2015). In cultured cells, Kim et al. found that MOTS-c moves into the cell nucleus under glucose restriction and regulates stress-response genes, a cell-culture result which does not establish the same action in people (Cell Metabolism, 2018). In cell-free tests and mice, Kumagai et al. found that it binds the enzyme CK2 and increases CK2 activity in mouse muscle and decreases it in mouse fat, a result that does not establish the same action in people (iScience, 2024).

Two cautions apply. FDA reviewers wrote in 2026 that the molecular target through which MOTS-c acts remains unknown, so the CK2 result is one proposed mechanism rather than a settled one (FDA briefing document, 11 May 2026). And the effects differ by tissue: in the same mice, MOTS-c raised CK2 activity in muscle and lowered it in fat, a tissue-specific mouse finding that does not establish human effects (Kumagai et al., 2024).

Have studies of MOTS-c found changes in fat or body weight?

No study showing fat loss in people was found in the sources searched for this page on 14 October 2026. In mice on a high-fat diet, Lee et al. reported that treated animals did not become obese while eating the same calories as untreated mice, a mouse result that does not establish weight or appetite effects in people (Cell Metabolism, 2015). In young mice Reynolds et al. found less fat gain with lean mass kept or raised, and in old mice lower fat mass, mouse results that do not establish effects in people (Nature Communications, 2021). In people, the registered Phase 2a trial NCT07505745, with 120 participants planned, names insulin sensitivity, not weight, as its primary outcome (ClinicalTrials.gov, checked 14 October 2026).

In a separate study of cold adaptation, MOTS-c treatment after cold exposure raised thermogenic gene activity in brown fat, increased the 'browning' of white fat and reduced fat traffic to the liver, an animal result that does not establish the same changes in people (Lu et al., International Journal of Molecular Sciences, 2019).

Results on appetite were not uniform in mice. Lee et al. saw modest drops in food intake in normal-diet mice after 4 days, yet in high-fat-fed mice calorie intake matched the untreated group, findings in mice that do not establish appetite effects in people (Cell Metabolism, 2015). In old treated mice, total food intake fell while body weight over their lifetime stayed similar, again in mice only, which does not establish appetite or weight effects in people (Reynolds et al., Nature Communications, 2021).

In people, studies describe the body's own MOTS-c, not MOTS-c given as a treatment. In a 2026 study of 22 lean and 32 obese adults, circulating MOTS-c was higher in obesity (273 versus 223 pg/mL) and unchanged in 10 patients six months after weight-loss surgery, an association in a small exploratory group (Yoon et al., Journal of Clinical & Translational Endocrinology, 2026). A 2024 meta-analysis of seven studies (six case-control and one cross-sectional) with 602 participants found lower blood MOTS-c in type 2 diabetes and higher levels in obesity, observational data from studies that differed in population (Zhou et al., Diabetology & Metabolic Syndrome, 2024).

The only human trial result found that touches weight belongs to CB4211, a modified MOTS-c analog, so it is not a result for MOTS-c. In the 4-week Phase 1b stage, 20 adults with fatty liver disease (11 on CB4211 and 9 on placebo) showed a trend toward lower body weight, and liver fat fell by similar amounts on CB4211 and on placebo (5.03% and 4.88% in the company's table), topline figures from a company filing and not a peer-reviewed paper (CohBar annual report filed 29 March 2022).

Has MOTS-c been studied in skin?

No study of MOTS-c on human skin was found in the sources searched for this page on 14 October 2026, and neither registered trial that gives MOTS-c or an analog to people lists a skin-health outcome (ClinicalTrials.gov, checked 14 October 2026). A PubMed search of titles and abstracts for MOTS-c together with the word skin returned two records on the same date. One reports that in mice given D-galactose, a sugar used to mimic ageing, MOTS-c treatment eased abnormal fat deposits in liver, visceral fat and dermal skin, a single mouse model that is an early lead and not evidence about human skin (Li et al., Biochemical and Biophysical Research Communications, 2019). The other is a mouse study that did not measure skin (the second record's title and abstract were screened on 14 October 2026).

In primary human fibroblasts (connective-tissue cells) pushed into senescence, a state in which cells stop dividing and release inflammatory signals, MOTS-c modestly raised mitochondrial respiration and selected components of the signals those cells release; this cell-culture result does not establish skin effects in people (Kim et al., Aging, 2018).

Two nearby findings are easy to mistake for human skin results. In a 2026 animal study of ischaemic surgical flaps (tissue moved from one body site to another), MOTS-c treatment was followed by improved blood flow and flap survival; the abstract does not specify the species, and this animal result does not establish skin ageing effects in people (Shi et al., Autophagy, 2026). In a human bone-forming cell line, MOTS-c raised type I collagen gene and protein levels; this experiment used no skin cells and does not establish skin effects in people (Che et al., European Review for Medical and Pharmacological Sciences, 2019).

Skin does appear in the record of CB4211, a different molecule. The sponsor's annual report for fiscal year 2022 says the Phase 1a/1b trial of CB4211 was suspended in November 2018 to address reactions at the site where the drug was given; this is a company statement about an analogue, gives no participant count for the Phase 1a stage in healthy subjects, is not a peer-reviewed result and does not establish MOTS-c safety (CohBar Form 10-K for fiscal year 2022, filed 9 March 2023).

Have studies reported sleepiness with MOTS-c?

The studies, registry records and regulator documents reviewed here did not report sleepiness as an effect of MOTS-c. FDA's searches of its adverse event reporting system (FAERS) for MOTS-c through 9 March 2025 retrieved no reports, a reporting search and not a safety trial, and FDA did not identify any clinical studies or human exposure data (FDA briefing document, 11 May 2026). The TGA lists insomnia and extreme tiredness among adverse events and concerns received for unapproved peptide products as a group, without naming MOTS-c (TGA, 13 April 2026). Studies that link MOTS-c to sleep measure the body's own level in people with sleep disorders, which says nothing about an effect of the peptide.

Where sleep appears in the MOTS-c literature, it appears as a disease marker. In 53 people with obstructive sleep apnea and 24 controls, serum MOTS-c was lower in people with more severe apnea, an association in a small study of the body's own peptide (Luo et al., Sleep and Biological Rhythms, 2025). In 70 patients with obstructive sleep apnea and 20 healthy controls, serum MOTS-c was lower with greater apnea severity and correlated negatively with the apnea-hypopnea index (the count of breathing pauses per hour of sleep; r = -0.492); this observational association did not test supplied MOTS-c (Baylan and Yarar, Sleep and Breathing, 2021).

In a 2019 study of blood immune cells from 10 people with chronic fatigue syndrome and 10 with Q fever fatigue syndrome, activity of the gene that encodes MOTS-c was lower than in 10 healthy controls, an association in a small sample that does not show MOTS-c changes tiredness in either direction (Raijmakers et al., Journal of Translational Medicine, 2019).

USADA reports that among people who claim to have bought MOTS-c online there are many reported side effects, including increased heart rate or palpitations, irritation at the site of use, insomnia, local or generalised immune reactions and fever; the page gives no count and no study design, so these are not trial results or a measured rate (USADA, page read 14 October 2026).

Have studies reported anxiety with MOTS-c?

No study found in the sources searched reports that MOTS-c causes anxiety. In a 2026 rat model of autism, valproic acid exposure produced impaired sociability, repetitive behaviours and anxiety, and MOTS-c treatment reversed all of these except anxiety and neocortical damage, a rat result with no human data behind it (Güvenir Seven et al., Molecular Neurobiology, 2026). A PubMed search of titles and abstracts for MOTS-c with anxiety-related terms returned only that record on 14 October 2026. No human study measuring anxiety after MOTS-c was found, and the registry record for the Phase 2a trial lists adverse events but no anxiety scale (ClinicalTrials.gov NCT07505745).

Whether MOTS-c given in the body reaches the brain is itself uncertain. In a 2021 mouse study, the authors reported that MOTS-c did not cross the blood-brain barrier, which led them to build a cell-penetrating analogue to carry it in; this mouse result does not establish human brain penetration (Jiang et al., ACS Chemical Neuroscience, 2021).

The registered Phase 2a trial, with 120 participants planned, lists treatment-emergent adverse events through 16 weeks as a primary outcome, and its record names no mood or sleep measure. No results are posted (ClinicalTrials.gov NCT07505745, checked 14 October 2026).

Are there human clinical trials of MOTS-c?

As of 14 October 2026, ClinicalTrials.gov holds one trial that gives MOTS-c to people: NCT07505745, a Phase 2a study with an industry sponsor, recruiting in Shenzhen, China since 2 February 2026, with 120 participants planned. Its primary outcomes are the change in insulin sensitivity at 12 weeks and adverse events through 16 weeks, and no results are posted. A search for the term MOTS-c returned nine records in total; the other eight list no MOTS-c intervention (ClinicalTrials.gov, 14 October 2026).

The PubMed trials that mention MOTS-c measure the body's own peptide. In a trial that randomised 30 volunteers to endurance exercise, resistance exercise or no exercise, blood MOTS-c showed a trend toward higher levels after endurance exercise while humanin rose significantly; this small exercise trial did not test supplied MOTS-c (von Walden et al., Journal of Applied Physiology, 2021). In a secondary analysis of a 16-week exercise trial in 49 breast cancer survivors (24 non-Hispanic White and 25 Hispanic), MOTS-c rose in non-Hispanic White participants and the rise tracked with reductions in fat mass; this small association study measured the natural peptide and did not test supplied MOTS-c (Dieli-Conwright et al., Scientific Reports, 2021).

CB4211 is the nearest thing to a completed human trial. Its sponsor described CB4211 as a novel and improved analog of MOTS-c, and its Phase 1a/1b study ran from 9 July 2018 to 19 April 2021 with 88 participants (ClinicalTrials.gov NCT03998514; CohBar annual report filed 29 March 2022). In the 88-participant trial (healthy adults and adults with fatty liver disease) the company reported no serious adverse events, and in the 4-week Phase 1b stage (adults with fatty liver disease, 11 on CB4211 and 9 on placebo) it reported that the liver enzyme ALT fell 21% on CB4211 against a 4% rise on placebo, and AST fell 28% against 11%; these are company figures for a different molecule, and the registry posts no results (CohBar annual report filed 29 March 2022; ClinicalTrials.gov NCT03998514). The half-life page covers what the registry lists for it.

Which reviews describe the clinical status of MOTS-c?

Reviews published from 2023 to 2026 describe MOTS-c as a research molecule without an established clinical use. In a narrative review, Zheng et al. write that MOTS-c has been used less frequently in disease treatment and that no effective method of applying it in the clinic has been developed (Frontiers in Endocrinology, 2023). In a review of 12 marketed peptides, MOTS-c among them, Mendias and Awan report that rigorous human safety data for unapproved peptides are scarce (Sports Medicine, 2026). A 2026 review of inflammatory lung disease says well-designed translational and multicenter clinical studies are needed to determine whether modulation or supplementation of MOTS-c can influence disease progression, and it tested nothing itself (Amado et al., Journal of Translational Medicine, 2026).

The reviews above describe human evidence as limited, and the primary studies on this page cannot settle how far a mouse result carries to people. For the regulatory side of that gap, the MOTS-c legal status page sets out what the TGA, FDA and WADA have published.