MOTS-c:
A Review of
Mitochondrial-Derived Peptide Research
A plain-language summary of published preclinical and observational research on the mitochondria-derived peptide MOTS-c, with a full account of its current human trial status
A Phase 2a human trial (NCT07505745) is currently recruiting but has not reported results. Results observed in animal models do not establish that equivalent effects will occur in humans. This content makes no claim that MOTS-c prevents, treats, or cures any disease or health condition. MOTS-c is supplied by Union Biolabs strictly as a research compound for laboratory use only. It is not a medicine. It is not approved for human use. This article is intended for researchers reviewing the published literature.
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome — a rare example of a signalling molecule derived from mitochondrial rather than nuclear DNA. First described by Lee and colleagues in 2015, MOTS-c has since been the subject of a growing body of preclinical research spanning metabolic regulation, exercise physiology, cardiac function, ageing biology, and immune modulation. Human observational studies have reported associations between lower circulating MOTS-c levels and various metabolic conditions. One Phase 2a randomised, placebo-controlled human trial is currently active (NCT07505745, recruiting). No completed, results-reported human efficacy trial exists in the published literature as of June 2026. This review presents all key published findings, clearly separates animal from human evidence, and contextualises what is and is not established at each evidence stage.
Background: What Is MOTS-c?
MOTS-c is a short peptide — a chain of just 16 amino acids — that is encoded not by the cell's nuclear DNA (as most proteins are), but by the mitochondrial genome. Specifically, it originates from a short open reading frame within the 12S ribosomal RNA region of mitochondrial DNA. This makes it a member of a small family of molecules called mitochondrial-derived peptides (MDPs), which includes humanin and the SHLP family.
The peptide is detectable in blood plasma, skeletal muscle, and multiple other tissues. Published studies have reported that plasma MOTS-c concentrations change in response to metabolic states and physical activity in experimental settings. Its levels have been observed to decline with age in both human blood samples and mouse tissues in published observational studies.
It is highly conserved across species — meaning the amino acid sequence is nearly identical between humans, mice, and other mammals — which is noted in the literature as suggesting fundamental biological importance, though conservation alone does not establish function in humans.
Research context: MOTS-c as an exogenously administered research compound has been studied exclusively in animal models and cell systems. The finding that endogenous MOTS-c levels change in human blood does not establish that administering exogenous MOTS-c produces equivalent or beneficial effects in humans.Mechanism of Action: What Laboratory Research Describes
Published research characterises several molecular pathways through which MOTS-c appears to act in experimental systems. The primary mechanism described involves activation of AMP-activated protein kinase (AMPK) — a cellular energy sensor that, when active, promotes pathways associated with glucose uptake, fatty acid oxidation, and metabolic adaptation.
A second mechanism, described in more recent publications, involves nuclear translocation: under conditions of metabolic stress in cell models, MOTS-c has been reported to translocate from the mitochondrial compartment into the cell nucleus, where it interacts with transcription factors to alter nuclear gene expression. This retrograde mitochondrial-to-nuclear signalling has been proposed as the basis for some of MOTS-c's observed effects on cellular stress responses in experimental systems.
Additional mechanistic observations in the published literature include modulation of the folate cycle and one-carbon metabolism — pathways involved in nucleotide synthesis and cellular methylation reactions — and effects on heat shock factor 1 (HSF1)-dependent stress responses in cell culture models.
Research context: Mechanistic pathways described above are characterised in cell culture experiments and animal studies. Whether these mechanisms operate in the same way, at the same concentrations, in human physiology is not established. AMPK activation and nuclear translocation have been demonstrated in experimental systems; their relevance to human pharmacology of exogenous MOTS-c administration remains to be determined by human trials.Observational Human Data: Endogenous MOTS-c Levels
A body of observational research has measured endogenous MOTS-c concentrations in blood samples from human participants across different health states. These are association studies — they describe relationships between MOTS-c levels and conditions, but do not establish causality, and do not involve administration of exogenous MOTS-c to any participant.
3.1 — Metabolic Conditions
Published studies have reported statistically lower blood MOTS-c concentrations in adults with type 2 diabetes (Ramanjaneya et al., 2019), in women with gestational diabetes (Yin et al., 2022), in individuals with coronary endothelial dysfunction (Qin et al., 2018), and in obese children and adolescents (Du et al., 2018), compared to non-affected controls in the respective studies.
Research context: These are observational associations. Lower circulating MOTS-c in individuals with metabolic conditions does not establish that low MOTS-c causes those conditions, nor that supplementing with exogenous MOTS-c would reverse them. Confounding factors (diet, activity, medication, metabolic disease severity) are not fully controlled for across these studies.3.2 — Age-Related Decline
Multiple publications have reported that plasma MOTS-c concentrations decline with advancing age in both human cohorts and mouse models. This age-dependent pattern has been noted as contextually relevant given MOTS-c's proposed role in mitochondrial function, though the causal direction of this relationship remains unclear in published literature.
3.3 — Exercise and Physical Activity
A 2021 publication by Reynolds, Lai, Woodhead, and colleagues in Nature Communications reported that endogenous skeletal muscle and plasma MOTS-c levels increased in healthy young male volunteers following acute exercise on a stationary bicycle. This was an observational measurement in a small cohort of healthy individuals, not an interventional study of exogenous MOTS-c.
Journal: Nature Communications 2021;12:773 · Participants: Small cohort of healthy young male volunteers
Method: Measurement of endogenous skeletal muscle and plasma MOTS-c before and after acute bicycle exercise
Reported Finding: MOTS-c levels increased in skeletal muscle and plasma following acute exercise in the study participants.
Limitation: Observational only. Small sample. Healthy young males only — not representative of broader populations. Does not involve exogenous MOTS-c. Does not establish what effect, if any, administering exogenous MOTS-c has in humans.
3.4 — Exercise Oncology Observational Study
A 2021 study by Dieli-Conwright, Sami, and colleagues in Scientific Reports measured MOTS-c levels in breast cancer survivors randomised to an exercise programme or usual care. This was a secondary, exploratory measurement within a larger trial. The study reported that exercise was associated with changes in MOTS-c levels in this population. The authors noted this as a novel marker for study in exercise oncology, describing the finding as preliminary.
Research context: The above is an exploratory secondary analysis in a specific patient population. It is observational with respect to MOTS-c. It does not involve administration of exogenous MOTS-c and cannot be used to make claims about the effects of MOTS-c as a research compound.Metabolic Research in Animal Models
4.1 — The Founding Study: Lee et al. (2015, Cell Metabolism)
The paper that first identified and characterised MOTS-c was published by Lee, Zeng, Drew, and colleagues — including senior author Pinchas Cohen — in Cell Metabolism in 2015. It established MOTS-c as a mitochondrially encoded signalling peptide and reported the first in vivo metabolic effects in mouse models.
In high-fat diet-fed mice, systemic MOTS-c administration was reported to prevent diet-induced obesity and insulin resistance. In aged mice, MOTS-c treatment was associated with improved insulin sensitivity. Food intake was reported as not significantly affected, suggesting that any metabolic effects in these models were not attributable to appetite suppression. The study also reported mechanistic evidence for AMPK activation and effects on the folate cycle in cell models.
Research context: This is a mouse study. Diet-induced obesity models in inbred mice do not replicate human metabolic disease. Results from this foundational study have not been reproduced in published human interventional trials. The sample sizes, species, and experimental conditions are specific to the laboratory models used.Journal: Cell Metabolism 2015;21(3):443–454 · Institution: USC Longevity Institute / NIA
Models: High-fat diet mice; aged mice; in vitro cell assays
Reported Findings: MOTS-c administration prevented diet-induced obesity and age-dependent insulin resistance in mouse models. No significant effect on food intake. AMPK activation and folate cycle modulation observed in cell models.
Limitations: Mouse model only. Inbred strains on artificial diets. No human data. Foundational paper — findings require replication and translational validation.
4.2 — Pancreatic Islet and Diabetes Research (Multiple Studies, 2022–2025)
A series of animal studies have examined MOTS-c in the context of pancreatic beta-cell biology. A 2025 publication by Kong, Lee, and colleagues in Experimental and Molecular Medicine reported that MOTS-c levels declined with ageing and senescence in pancreatic islet cells in mice and human datasets. In mouse models, MOTS-c treatment was reported to reduce markers of pancreatic islet cell senescence and improve glucose tolerance in chemically induced diabetic mice.
Earlier studies (Li et al., 2022; Xu et al., 2024) reported MOTS-c administration was associated with lower blood glucose in type 1 diabetic rat and mouse models, without significant effects on food intake in those experimental systems.
Research context: All findings above are from animal models of diabetes (mice and rats). The pathophysiology of type 1 and type 2 diabetes in chemically induced or genetically modified rodent models is an approximation only. None of these studies administered exogenous MOTS-c to human participants.Journal: Experimental and Molecular Medicine (2025) · Institution: Seoul National University Hospital
Models: Aged C57BL/6 mice; NOD mice; S961-treated mice; human islet dataset analysis (observational)
Reported Findings: MOTS-c levels declined with ageing in islets. MOTS-c treatment reduced islet senescence markers and improved glucose tolerance in mouse models.
Limitations: Mouse models and observational human dataset analysis only. No interventional human data.
Exercise and Physical Performance Research in Animal Models
The relationship between MOTS-c and physical performance has been one of the most extensively studied areas in the published literature, motivated by both the observational finding that exercise increases endogenous MOTS-c in humans and the mechanistic hypothesis that MOTS-c may act as an exercise-induced mitochondrial signal.
5.1 — Reynolds, Lai, Woodhead et al. (2021, Nature Communications)
This study combined the human observational exercise data (described in Section 3.3) with mouse experiments in which exogenous MOTS-c was administered daily to young, middle-aged, and old mice. In the mouse component, MOTS-c treatment was reported to improve treadmill running performance and physical capacity across age groups. Metabolic and transcriptomic analyses of skeletal muscle were also conducted.
Journal: Nature Communications 2021;12:773
Animal component: Daily MOTS-c (5 mg/kg IP) in young, middle-aged, and old mice · Treadmill and rotarod performance assessed · Skeletal muscle metabolomics and transcriptomics conducted
Human component: Observational measurement of endogenous MOTS-c in healthy young males before and after exercise only — no exogenous MOTS-c administered to humans
Reported Animal Findings: Improved treadmill running across all age groups vs vehicle. Altered skeletal muscle metabolomic and transcriptomic profiles.
Limitations: Animal performance data only for exogenous MOTS-c. Human data is observational only. Cannot be used to make claims about MOTS-c effects on human physical performance.
Cardiac Research in Animal Models
6.1 — Diabetic Heart Function: Pham et al. (2025, Frontiers in Physiology)
A 2025 study from the University of Auckland examined MOTS-c treatment in a rat model of type 2 diabetes induced by high-fat diet combined with low-dose streptozotocin injection. The study focused on mitochondrial respiration in cardiac tissue — specifically whether MOTS-c could restore the mitochondrial energy production capacity that is reported to decline in diabetic heart tissue in animal models.
MOTS-c treatment was reported to improve mitochondrial respiratory function in isolated cardiac tissue from the diabetic rat model, and to be associated with delayed weight gain in treated animals without significant effect on food intake. The authors noted that these findings were consistent with earlier mouse studies (Lee et al., 2015).
Research context: This study was conducted in rats using a chemically induced diabetes model. Rat cardiac physiology and human diabetic heart disease are not equivalent. Mitochondrial respiration was measured in isolated cardiac tissue preparations, not in a functioning heart in a living human. No human cardiac data is available for exogenous MOTS-c.Journal: Frontiers in Physiology 2025;16:1602271 · Institution: University of Auckland
Model: High-fat diet + low-dose STZ T2D rat model
Reported Findings: MOTS-c treatment reported to restore mitochondrial respiratory capacity in isolated cardiac tissue from diabetic rats. Associated with delayed weight gain vs vehicle-treated diabetic controls.
Limitations: Rat model. Chemically induced diabetes. Cardiac tissue measurements in isolated preparations. No human cardiac data. No clinical endpoint (survival, cardiac function in living animals over extended periods).
6.2 — Cardiac Function and Exercise in Diabetic Rats: Li et al. (2022, Frontiers in Endocrinology)
This study examined the combination of MOTS-c treatment and aerobic exercise in diabetic rats, using cardiac transcriptomics to characterise molecular changes. The combination was reported to be associated with improved cardiac function markers and activation of neuregulin-1 (NRG1) and ErbB signalling pathways in the rat heart. The authors described MOTS-c as having exercise-like effects in this experimental system based on observed molecular signatures.
Research context: Rat model only. Molecular pathway activation in diabetic rat cardiac tissue cannot be used to characterise effects of MOTS-c on human cardiovascular function.Ageing and Longevity Research in Animal Models
MOTS-c has attracted interest in ageing biology research partly because of the observed age-dependent decline in its circulating levels in both humans and mice, and partly because of its mitochondrial origin — mitochondrial dysfunction being widely studied as a contributor to cellular ageing processes.
Published animal studies have examined whether exogenous MOTS-c can restore markers of metabolic function in aged animals. The Reynolds et al. (2021) study in Nature Communications reported improved treadmill performance in aged (22-month) mice. Other studies have examined MOTS-c's effects on cellular senescence markers in mouse pancreatic and muscle tissue.
A study examining muscle atrophy during immobilisation in an animal model (published 2024, PMID 38170165) reported that MOTS-c attenuated markers of muscle atrophy and suppressed lipid infiltration in the immobilised muscle in the experimental model studied.
Research context: All ageing-related findings described above are from animal models. Aged mouse physiology is an experimental approximation only. The processes underlying human ageing are substantially more complex and heterogeneous than those in inbred mouse strains. No interventional human data on ageing-related outcomes of exogenous MOTS-c exists in the published literature.Other Research Areas: Immune Modulation and Oncology
8.1 — Immune Research in Mouse Models
Published animal studies have examined MOTS-c in the context of immune regulation, particularly in non-obese diabetic (NOD) mouse models — a strain that spontaneously develops autoimmune diabetes. MOTS-c treatment in these models was reported to modulate T-cell differentiation and reduce pancreatic immune infiltration in the experimental system studied.
Research context: NOD mouse autoimmune disease is a laboratory model. Human autoimmune diabetes involves substantially more complex and individually variable immune mechanisms. No human immune data for exogenous MOTS-c exists.8.2 — Oncology Observational Research
A 2024 study published in Advanced Science (Yin et al.) reported that MOTS-c levels were lower in serum and tumour tissue samples from ovarian cancer patients compared to controls, and that low MOTS-c levels were associated with poorer prognosis in the cohort studied. Cell culture experiments in that study reported that exogenous MOTS-c inhibited ovarian cancer cell proliferation and migration in vitro. This research is observational and mechanistic in nature.
Research context: Observational association between MOTS-c levels and cancer prognosis does not establish causality. In vitro cancer cell behaviour does not predict in vivo or clinical outcomes. This is exploratory, hypothesis-generating research. No animal tumour model or human interventional data on MOTS-c in oncology has been published.Preclinical Dose Ranges Used in Published Animal Studies
The following table compiles dose ranges, routes of administration, species, and durations reported across key published studies on exogenous MOTS-c in animal models. This is a factual summary of published experimental methodology compiled for researchers reviewing the preclinical dataset.
| Published Study | Species / Model | Dose Used | Route | Duration |
|---|---|---|---|---|
| Lee et al. 2015 (Cell Metabolism) | C57BL/6 mice · HFD and aged models | Range reported | Intraperitoneal (IP) | Multiple weeks |
| Reynolds et al. 2021 (Nat Commun) | CD-1 and C57BL/6N mice · young, mid-aged, old | 5 mg/kg/day | Intraperitoneal (IP) | 2 weeks daily |
| Li et al. 2022 (Front Endocrinol) | Diabetic rats · HFD + STZ model | 0.5 mg/kg | Intraperitoneal (IP) | Multiple weeks |
| Yuan et al. 2021 | Rodent model | 0.5 mg/kg | Subcutaneous (SC) | Study-dependent |
| Xu et al. 2024 | T1D mouse model | 1 mg/kg | Intraperitoneal (IP) | Study-dependent |
| Yang et al. 2024 | Rodent model | 0.5 mg/kg | Intraperitoneal (IP) | Study-dependent |
| Zempo et al. (cited in literature) | Rodent model | 7.5 mg/kg | Intraperitoneal (IP) | Study-dependent |
In Vitro Concentrations Reported in Published Cell Studies
Cell culture studies (including Reynolds et al. 2021 preprint and Elhusseiny et al. 2026) report using MOTS-c at concentrations of approximately 10 μM in culture media. Lyophilised MOTS-c is reconstituted in sterile aqueous vehicle (typically saline or PBS) in published experimental protocols. Storage at −20°C for lyophilised material is referenced in published methodology.
Research context: Cell culture concentrations and reconstitution methodology are provided for reference to researchers designing in vitro experiments consistent with the published literature. Not applicable to human use.How MOTS-c Compares to Related Peptides in the Published Literature
Researchers studying MOTS-c frequently require context on how it relates to other mitochondrial-derived peptides (MDPs) and mechanistically similar compounds. The following comparison is drawn entirely from published literature.
10.1 — MOTS-c vs Humanin
Humanin is the best-characterised MDP and was identified before MOTS-c (Hashimoto et al., 2001). Both are encoded by the mitochondrial genome: MOTS-c from the 12S rRNA region; humanin from the 16S rRNA region. A 2026 in vitro study by Elhusseiny, Ihsan, and colleagues (Physiological Reports) directly compared both peptides in human skeletal muscle cell cultures, reporting that both attenuated dexamethasone-induced muscle atrophy markers in myotube preparations. Primary mechanistic difference in the literature: MOTS-c primarily activates AMPK and translocates to the nucleus; humanin primarily signals via JAK2/STAT3 and has been more studied in neuroprotective and cardiovascular contexts.
Journal: Physiological Reports, Feb 2026 · DOI: 10.14814/phy2.70791 · Model: Human skeletal muscle myotubes · dexamethasone-induced atrophy
Reported Finding: Both MOTS-c and humanin attenuated atrogene expression and preserved fusion index in dexamethasone-treated myotubes in this in vitro model.
Limitation: In vitro human cell culture only. Cannot be used to make claims about effects of either peptide in living humans.
10.2 — MOTS-c vs SHLP Peptides (Small Humanin-Like Peptides)
The SHLP family (SHLP1–6) was identified more recently, also from the mitochondrial 16S rRNA region. They have substantially less published research than MOTS-c or humanin. SHLP2 has attracted particular interest for beta-cell effects in cell models. The entire MDP family — MOTS-c, humanin, and the SHLPs — is considered an emerging research area without established human clinical data for any member.
10.3 — MOTS-c and Mechanistic Overlap with Metformin
Published reviews note that MOTS-c and metformin share AMPK activation as a downstream pathway in experimental systems. This mechanistic overlap has led some researchers to describe MOTS-c as a "mitochondrial hormone" with some parallel downstream biology. They are structurally completely different — metformin is a small-molecule biguanide; MOTS-c is a 16-amino-acid peptide. Published literature notes that whether they would share or diverge in safety profiles in humans is unknown.
Research context: Mechanistic overlap at the AMPK level does not mean clinical equivalence. Metformin has decades of human data; MOTS-c has none. This is a mechanistic literature observation only.10.4 — Comparison Table: Published Literature Features
| Feature | MOTS-c | Humanin | SHLPs (1–6) |
|---|---|---|---|
| Amino acid length | 16 aa | 21–24 aa | 21 aa (each) |
| Mitochondrial origin | 12S rRNA | 16S rRNA | 16S rRNA |
| Primary pathway (preclinical) | AMPK; nuclear translocation | JAK2/STAT3; Bcl-2 | Variable by SHLP |
| Main research focus in literature | Metabolism; exercise; ageing | Neuroprotection; cardiovascular; beta-cell | Beta-cell; metabolic (SHLP2) |
| Age-related decline (observational) | Yes — human & mouse data | Yes — human data | Limited data |
| Published animal studies | Extensive (20+) | Extensive (30+) | Limited (5–10) |
| Human interventional trial | 1 active — NCT07505745 (no results) | Related compound CB4211 Phase 1a completed | None published |
| WADA prohibited (2024) | Yes | Not currently listed | Not listed |
Preclinical Safety Data
Published animal studies on MOTS-c have generally reported no significant adverse effects in treated animals at the doses studied. The doses used in published mouse and rat experiments range from 0.5 to 7.5 mg/kg administered by intraperitoneal or subcutaneous injection, with durations ranging from days to several weeks.
No published chronic toxicology study (the type required before human trials) has been identified in the available literature for MOTS-c. The active Phase 2a clinical trial (NCT07505745) implies that IND-enabling safety studies have been completed to allow human administration, but these data have not been published in the peer-reviewed literature as of June 2026.
| Safety Parameter | Preclinical (Animal) Evidence | Human Safety Evidence |
|---|---|---|
| Acute toxicity | No toxicity reported at doses studied in mice/rats | Phase 2a trial underway (safety is primary endpoint) — no results yet |
| Food intake effects | No significant effect reported in multiple studies | No human data |
| Immunogenicity | Not specifically reported in published preclinical studies | Assessed as secondary endpoint in Phase 2a trial — no results yet |
| Chronic / long-term safety | Not studied beyond several weeks in published work | No published human data |
| Cardiovascular safety | Cardiac studies in rat models — no dedicated safety endpoint | No published human data |
| WADA status | — | Prohibited in sport by WADA as of 2024 |
The Active Human Clinical Trial: NCT07505745
One registered human clinical trial of exogenous MOTS-c is currently active and recruiting as of June 2026. This represents the first progression of MOTS-c into a controlled human interventional study and is an important milestone in the research programme.
"The Phase 2a trial does not prove MOTS-c works in humans. It is designed to test whether measurable changes in insulin sensitivity can be detected — and to assess safety. Results are not yet available."
Trial ID: NCT07505745 · Phase: 2a · Design: Randomised, double-blind, placebo-controlled
Population: Adults with prediabetes and overweight or obesity
Duration: 16 weeks of treatment
Primary Endpoints: (1) Change in insulin sensitivity from baseline, measured by Matsuda Index from oral glucose tolerance test (OGTT); (2) Treatment-emergent adverse events (safety)
Secondary Endpoints: HbA1c; fasting glucose; 2-hour glucose on OGTT; immunogenicity
Status: Recruiting — no results published as of June 2026
Important note: Registration of a clinical trial does not constitute evidence of efficacy. The trial is designed to generate evidence, not to confirm it. Results — whether positive, negative, or inconclusive — are not available at the time of this review.
Research Timeline: Key Publications and Milestones
Complete Study Register
First identification of MOTS-c. HFD and aged mouse models. Diet-induced obesity and insulin resistance prevented in mice. AMPK activation. MOUSE DATA ONLY.
Review of MOTS-c mechanism in muscle and fat metabolism. Summary of evidence available at time of publication.
Lower plasma MOTS-c associated with coronary endothelial dysfunction in study cohort. Observational. No exogenous MOTS-c administered.
Lower blood MOTS-c reported in adults with type 2 diabetes vs controls. Observational. No exogenous MOTS-c administered.
Lower MOTS-c in obese children and adolescents vs lean controls. Observational. No exogenous MOTS-c administered.
MOTS-c levels measured as exploratory secondary endpoint in breast cancer survivors randomised to exercise vs usual care. No exogenous MOTS-c. Exploratory finding.
Endogenous MOTS-c increased in skeletal muscle and plasma of healthy young males following acute bicycle exercise. Small cohort. Observational. No exogenous MOTS-c administered to any human participant.
Lower MOTS-c in women with gestational diabetes vs controls. Observational. No exogenous MOTS-c administered.
Lower MOTS-c in serum and tumour tissue from OC patients; associated with poorer prognosis. In vitro: exogenous MOTS-c inhibited OC cell growth. Observational + cell culture. No human interventional data.
MOTS-c 5 mg/kg daily IP in young, middle-aged, old mice. Treadmill performance improved across age groups vs vehicle. Skeletal muscle metabolomics and transcriptomics. MOUSE DATA ONLY.
Diabetic rats. MOTS-c ± aerobic exercise. Cardiac transcriptomics. NRG1-ErbB pathway activation reported. RAT DATA ONLY.
Aged C57BL/6, NOD, and S961 mice. MOTS-c reduced islet senescence markers; improved glucose tolerance in mouse models. MOUSE DATA ONLY.
HFD + STZ T2D rat model. MOTS-c reported to restore cardiac mitochondrial respiration in isolated tissue preparations. RAT DATA ONLY.
MOTS-c reported to attenuate immobilisation-induced muscle atrophy and suppress lipid infiltration in experimental model. ANIMAL DATA ONLY.
Phase 2a · Randomised, double-blind, placebo-controlled · Adults with prediabetes + overweight/obesity · 16 weeks · Primary: Matsuda Index insulin sensitivity + safety · Secondary: HbA1c, glucose, immunogenicity · Recruiting June 2026 · NO RESULTS AVAILABLE
Key References
- Lee C, Zeng J, Drew BG et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015;21(3):443–454.
- Lee C, Kim KH, Cohen P. MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016;100:182–187.
- 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;12:773.
- Dieli-Conwright CM, Sami N, Norris MK et al. Effect of aerobic and resistance exercise on MOTS-c in breast cancer survivors. Sci Rep. 2021;11:16916.
- Li S, Wang M et al. MOTS-c and exercise restore cardiac function by activating NRG1-ErbB signaling in diabetic rats. Front Endocrinol. 2022;13:812032.
- Yin Y et al. MOTS-c suppresses ovarian cancer progression by attenuating USP7-mediated LARS1 deubiquitination. Adv Sci. 2024;11:2405620.
- Kong BS, Lee H et al. MOTS-c prevents pancreatic islet cell senescence to delay diabetes. Exp Mol Med. 2025. doi:10.1038/s12276-025-01521-1.
- Pham T, Taberner A, Hickey A, Han JC. MOTS-c restores mitochondrial respiration in type 2 diabetic heart. Front Physiol. 2025;16:1602271.
- Ramanjaneya M et al. Mitochondrial-derived peptides are down regulated in diabetes subjects. Front Endocrinol. 2019.
- Phase 2a Clinical Trial: NCT07505745. ClinicalTrials.gov. Active — recruiting June 2026.
Full Legal & Research Disclaimer
Nature of this content: This article is a summary of published peer-reviewed scientific literature on MOTS-c. It is written for researchers and scientists reviewing the academic evidence base. It does not constitute medical advice, health guidance, or a product recommendation of any kind.Evidence limitations: The majority of efficacy findings described are from animal studies (mice and rats) and in vitro experiments. Human observational data relates to measurement of endogenous MOTS-c levels — not to administration of exogenous MOTS-c. One human clinical trial is active but has not reported results. Animal model findings do not establish that equivalent effects occur in humans.
Product status: MOTS-c is supplied by Union Biolabs exclusively as a research compound for qualified laboratory use only. It is not a medicine. It has not been approved or licensed by the MHRA, FDA, EMA, or any other regulatory body for any therapeutic purpose. It is not intended for human consumption, self-administration, or use outside a controlled laboratory research setting. It is prohibited in sport by the World Anti-Doping Agency (WADA) from 2024.
No therapeutic claims: Nothing in this article constitutes a claim that MOTS-c prevents, treats, cures, or mitigates any disease or health condition in humans. The existence of an active clinical trial does not constitute evidence of efficacy — trials may return negative, positive, or inconclusive results. Researchers are responsible for compliance with all applicable regulations in their jurisdiction.
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