{"site":"MOTS-c Co","url":"https://motscco.com","format":"evidence-manifest/v1","claim_count":80,"claims":[{"id":"clm-001","text":"MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial 12S ribosomal RNA gene (MT-RNR1); its full name is mitochondrial open reading frame of the 12S rRNA type-c.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://motscco.com/entity","https://motscco.com/llms","https://motscco.com/monograph"]},{"id":"clm-002","text":"MOTS-c has the molecular formula C101H152N28O22S2 and a molecular weight of 2174.6 g/mol; its sequence is H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH, and PubChem records it under CID 146675088 with CAS number 1627580-64-6.","source_url":"https://pubchem.ncbi.nlm.nih.gov/compound/146675088","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://motscco.com/entity","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-003","text":"FDA treats MOTS-c free base and MOTS-c acetate as two distinct bulk drug substances, and notes the acetate salt has molecular weight 2234.64 g/mol.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com/entity","https://motscco.com/monograph"]},{"id":"clm-004","text":"MOTS-c is a common name rather than a United States Adopted Name, and FDA states it has encountered multiple salts and derivatives, including different active moieties, sold commercially under the same common name.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-005","text":"MOTS-c is present in the systemic circulation of humans and rodents and is expressed in tissues including skeletal muscle, heart and brain; it appears highly conserved across species.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-006","text":"No FDA-approved drug product contains MOTS-c: a Drugs@FDA query for the active ingredient returns no matches.","source_url":"https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22mots-c%22&limit=3","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/entity","https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-007","text":"FDA's compounding safety-risks list states that it has not identified any human exposure data on drug products containing MOTS-c administered via any route of administration, and that it lacks important information about whether the drug would cause harm if administered to humans.","source_url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/entity","https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-008","text":"FDA's July 2026 PCAC briefing document proposed that MOTS-c (free base) and MOTS-c acetate both NOT be included on the 503A Bulks List.","source_url":"https://www.fda.gov/media/193342/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-009","text":"The MOTS-c nomination came from Wells Pharmacy Network and was withdrawn; FDA evaluated the substances at its own discretion, and the uses listed on FDA's meeting agenda were obesity and osteoporosis.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-010","text":"FDA's balancing of the 503A criteria weighs against placing MOTS-c free base or MOTS-c acetate on the list; advisory committee advice is non-binding and rulemaking is pending, and listing would make a substance eligible for compounding, not FDA approved.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-011","text":"As of the fetch date, FDA's meeting page for the July 2026 PCAC carried the agenda and briefing materials but no posted vote tally or minutes, so this site does not state how the committee voted.","source_url":"https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-012","text":"The nominated MOTS-c products were 5 mg and 10 mg vials for subcutaneous injection, nominated for insulin resistance, obesity, osteoporosis, vascular calcification, muscle and fat metabolism, and longevity.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-013","text":"FDA did not evaluate the nominated uses because the nomination lacked sufficient information and FDA did not identify clinical studies evaluating those uses of MOTS-c.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com/monograph"]},{"id":"clm-014","text":"The 2026 WADA Prohibited List names MOTS-c by full name under section S4.4.1, activators of AMP-activated protein kinase, within hormone and metabolic modulators, which are prohibited at all times.","source_url":"https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-015","text":"FDA notes MOTS-c appears as a prohibited substance in the Global Drug Reference Online database, sourced from the WADA prohibited list of hormone and metabolic modulators.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-016","text":"FDA states that its own literature search identified no clinical studies evaluating administration of MOTS-c to human subjects.","source_url":"https://www.fda.gov/media/193347/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-017","text":"FDA states the nomination did not include, and FDA has not identified, any clinical studies or human exposure data for MOTS-c via any route of administration, so potential human safety risks are unknown.","source_url":"https://www.fda.gov/media/193347/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/decision_aid","https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-018","text":"FDA's searches of its adverse event reporting system for MOTS-c through March 2025 retrieved no reports, which FDA notes is expected because compounders under section 503A generally do not report adverse events to FDA.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-019","text":"No published study was found in which compounded or non-compounded drug products containing MOTS-c were used in humans, and outsourcing facilities reported no MOTS-c compounding to FDA between January 2017 and December 2025.","source_url":"https://www.fda.gov/media/193347/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-020","text":"One randomized human trial of MOTS-c itself is registered: NCT07505745, a Phase 2a double-blind placebo-controlled study of subcutaneous MOTS-c once daily for 12 weeks in 120 planned adults with prediabetes and overweight or obesity, sponsored by Hudson Biotech at a site in Shenzhen, China, recruiting since February 2026 with no results posted.","source_url":"https://clinicaltrials.gov/study/NCT07505745","grade":"registry","grade_label":"Registry record","used_on":["https://motscco.com/copy","https://motscco.com/decision_aid","https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-021","text":"The registered Phase 2a MOTS-c trial does not state the dose in its public registry record; its regimen field says only a fixed dose once daily for 12 weeks.","source_url":"https://clinicaltrials.gov/study/NCT07505745","grade":"registry","grade_label":"Registry record","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-022","text":"A PubMed search of MOTS-c in titles and abstracts returned 248 records, and no record in that literature reports administering MOTS-c to human participants.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9057581/","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://motscco.com/copy","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-023","text":"CB4211 is an analog of MOTS-c, not MOTS-c itself; a peer-reviewed review states its intellectual property was licensed by CohBar and used to develop potent analogs of MOTS-c.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9057581/","grade":"review","grade_label":"Review or guideline","used_on":["https://motscco.com/comparison","https://motscco.com/entity","https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-024","text":"The CB4211 trial (NCT03998514) was a three-part Phase 1a/1b randomized, double-blind, placebo-controlled study of single and multiple ascending subcutaneous doses in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease, sponsored by CohBar, with 88 participants, completed 19 April 2021.","source_url":"https://clinicaltrials.gov/study/NCT03998514","grade":"registry","grade_label":"Registry record","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-025","text":"The CB4211 trial has no results posted on ClinicalTrials.gov, and a PubMed search for CB4211 returns zero records, so no peer-reviewed publication of that human data exists.","source_url":"https://clinicaltrials.gov/study/NCT03998514","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-026","text":"The CB4211 registry record never names MOTS-c: its listed condition is nonalcoholic fatty liver disease and its interventions are labeled only CB4211 dose levels and placebo.","source_url":"https://clinicaltrials.gov/study/NCT03998514","grade":"registry","grade_label":"Registry record","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-027","text":"FDA identified no in vivo pharmacokinetic or toxicokinetic studies of MOTS-c in any species, and no clinical study providing pharmacokinetic data.","source_url":"https://www.fda.gov/media/193347/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph","https://motscco.com/pk","https://motscco.com/tooldata"]},{"id":"clm-028","text":"The only pharmacokinetic-related study FDA identified was an in vitro experiment in which MOTS-c at 5 micrograms per mL was incubated in human whole blood at 37 degrees C for 15 or 60 minutes and was rapidly cut into the shorter fragments MOTS-c(2-16), (3-16), (4-16) and (5-16).","source_url":"https://www.fda.gov/media/193347/download","grade":"in-vitro","grade_label":"In vitro","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/pk","https://motscco.com/studies"]},{"id":"clm-029","text":"FDA states it remains to be determined whether giving MOTS-c to humans can generate pharmacologically active concentrations of the peptide over time.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph","https://motscco.com/pk"]},{"id":"clm-030","text":"The doping-control study that produced the human-blood degradation data was built to detect synthetic MOTS-c in athlete plasma samples by liquid chromatography and mass spectrometry.","source_url":"https://europepmc.org/article/MED/30394592","grade":"in-vitro","grade_label":"In vitro","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-031","text":"FDA identified no acute toxicity, repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity, or carcinogenicity studies of MOTS-c free base or MOTS-c acetate.","source_url":"https://www.fda.gov/media/193347/download","grade":"absence-of-evidence","grade_label":"Absence of evidence","used_on":["https://motscco.com/decision_aid","https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-032","text":"In the 2015 discovery paper, MOTS-c treatment in mice prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity, with effects attributed to inhibition of the folate cycle and de novo purine biosynthesis leading to AMPK activation.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-033","text":"In the discovery work, male CD-1 mice on a 60 percent fat diet given intraperitoneal MOTS-c at 0.5 mg/kg/day for 8 weeks weighed about 20 percent less than vehicle-treated mice, with increased energy expenditure and reduced liver fat.","source_url":"https://www.fda.gov/media/193347/download","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-034","text":"In the same work, mice given MOTS-c at 5 mg/kg/day intraperitoneally required about 30 percent higher glucose infusion rates to maintain euglycemia during insulin stimulation, and 7 days of that dose restored insulin sensitivity in soleus muscle of 12-month-old mice to the level of 3-month-old mice.","source_url":"https://www.fda.gov/media/193347/download","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-035","text":"In mice, acute MOTS-c at 5 mg/kg intraperitoneally improved treadmill performance in young, middle-aged and old animals, and intermittent treatment at 15 mg/kg three times per week begun at 23.5 months of age raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days.","source_url":"https://www.fda.gov/media/193347/download","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-036","text":"The 2021 Nature Communications paper reports that MOTS-c significantly enhanced physical performance in young, middle-aged and old mice, and that in humans exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7817689/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-037","text":"MOTS-c translocates to the nucleus and regulates nuclear gene expression after metabolic stress in an AMPK-dependent manner, interacting with stress-responsive transcription factors including NRF2, demonstrated in cell systems.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6185997/","grade":"in-vitro","grade_label":"In vitro","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-038","text":"A 2024 study reports MOTS-c binds and activates casein kinase 2 (CK2) in cell-free systems, that MOTS-c given to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake in a CK2-dependent way, and that the naturally occurring K14Q variant binds CK2 poorly and does not reproduce those effects.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11570452/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-039","text":"In ovariectomized mice, MOTS-c injected at 5 mg/kg once daily for 12 weeks reduced bone loss on micro-CT and inhibited RANKL-induced osteoclast differentiation, an effect partially blocked by an AMPK inhibitor.","source_url":"https://europepmc.org/article/MED/27237975","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-040","text":"In a mouse calvaria osteolysis model, MOTS-c injected locally reduced bone erosion and inflammation and raised the osteoprotegerin to RANKL ratio in osteocytes.","source_url":"https://europepmc.org/article/MED/31369811","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-041","text":"In cultured rat bone marrow mesenchymal stem cells, MOTS-c promoted osteogenic differentiation through the TGF-beta/Smad pathway.","source_url":"https://europepmc.org/article/MED/30468456","grade":"in-vitro","grade_label":"In vitro","used_on":["https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-042","text":"In a rat model of vascular calcification induced by vitamin D3 plus nicotine, MOTS-c at 5 mg/kg/day intraperitoneally for 4 weeks attenuated calcification and myocardial remodeling with restored AMPK phosphorylation.","source_url":"https://europepmc.org/article/MED/31694019","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-043","text":"In mice, MOTS-c increased brown fat thermogenic gene expression and white fat browning and improved cold tolerance, with serum MOTS-c falling after cold stress.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6567243/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-044","text":"In diet-induced obese mice, MOTS-c administration lowered plasma myostatin and prevented palmitic-acid-induced atrophy in cultured myotubes, with plasma MOTS-c inversely correlated with myostatin in human samples.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8238132/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-045","text":"In an immobilization model, mice given MOTS-c at 15 mg/kg/day lost about 5 percent muscle mass versus about 15 percent in immobilized controls, with normalized AKT and FOXO signaling and lower circulating inflammatory cytokines.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11196098/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-046","text":"In a mouse cancer-cachexia model, MOTS-c at 15 mg/kg twice daily preserved quadriceps mass by 12 percent versus vehicle but did not prevent total body weight or fat loss.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13243040/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies","https://motscco.com/tooldata"]},{"id":"clm-047","text":"In a high-fat-diet and streptozotocin rat model of type 2 diabetes, MOTS-c reduced fasting glucose and C-reactive protein and lowered NLRP3 inflammasome markers in left ventricular tissue.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13394035/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-048","text":"In an allergic asthma model, MOTS-c reduced lung tissue damage in mice and protected cultured human airway epithelial cells via the Nrf2 pathway; serum MOTS-c was lower in patients with asthma than in healthy volunteers.","source_url":"https://europepmc.org/article/MED/40472776","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-049","text":"FDA states that nonclinical pharmacology of MOTS-c is limited to in vivo and in vitro rodent models, has not evaluated dose-response relationships in vivo, and that the molecular targets through which MOTS-c acts remain unknown, making it difficult to predict which organs might be affected.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-050","text":"The East-Asian-specific mitochondrial variant m.1382A>C (rs111033358) changes the 14th amino acid of MOTS-c from lysine to glutamine, producing the K14Q variant.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/","grade":"chemical-reference","grade_label":"Chemical reference","used_on":["https://motscco.com/entity","https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-051","text":"A meta-analysis of three Japanese cohorts totalling 27,527 people found that men, but not women, carrying the C allele had a higher prevalence of type 2 diabetes, and in one cohort only among men in the lowest tertile of physical activity.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-052","text":"In the same study, high-fat-fed male mice injected with MOTS-c lost weight and improved glucose tolerance while mice given the K14Q variant peptide did not, and female mice were unaffected.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/","grade":"animal","grade_label":"Animal","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-053","text":"In 211 Japanese adults, C-allele carriers had a higher proportion of fast-twitch myosin heavy chain IIx; among 721 Japanese athletes and 873 controls the C allele was most common in sprint and power athletes (6.5 percent), then controls (5.1 percent), then endurance athletes (2.9 percent).","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8741734/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-054","text":"In 683 community-dwelling Korean adults aged 65 and older, men carrying the C allele had higher appendicular skeletal muscle mass, lean mass and handgrip strength than A-allele carriers, with no significant differences among women.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11504729/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-055","text":"The 2015 paper that started the longevity framing was a two-page hypothesis piece suggesting the m.1382A>C polymorphism may be among putative mechanisms for Japanese longevity, and it explicitly stated that more research is needed.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4693465/","grade":"review","grade_label":"Review or guideline","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-056","text":"In 10 lean and 10 obese adults, plasma MOTS-c concentrations were similar between groups (0.48 versus 0.52 ng/mL, p=0.60) and correlated with insulin-resistance indexes mainly in the lean group.","source_url":"https://europepmc.org/article/MED/29593067","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-057","text":"In 40 obese and 57 control children and adolescents, circulating MOTS-c was lower in the obese group (472.61 versus 561.64 ng/mL, p<0.01), a difference present in boys and not in girls.","source_url":"https://europepmc.org/article/MED/29691953","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-058","text":"A 2026 Mayo Clinic study found circulating MOTS-c higher in adults with obesity than lean controls (273 versus 223 pg/mL, p<0.01) and unchanged six months after bariatric surgery despite significant weight loss.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12807633/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-059","text":"A 2024 meta-analysis of seven studies covering 602 participants found circulating MOTS-c decreased in diabetes but increased in obesity, results the authors describe as opposite directions after subgroup analysis.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11331736/","grade":"meta-analysis","grade_label":"Meta-analysis","used_on":["https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-060","text":"In healthy aging men, circulating MOTS-c fell with age while skeletal muscle MOTS-c expression was about 1.5-fold higher in middle-aged and older men than in young men, tracking myofiber composition.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7138593/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-061","text":"In 125 Chinese adults without diabetes, plasma MOTS-c was elevated in those with metabolic syndrome and associated most strongly with waist circumference and liver fat.","source_url":"https://europepmc.org/article/MED/34419510","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-062","text":"In 121 people with type 2 diabetes after revascularization, MOTS-c below 167 ng/mL predicted major adverse cardiac events over two years alongside high on-clopidogrel platelet reactivity.","source_url":"https://europepmc.org/article/MED/32052315","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-063","text":"In 20 physically active adults, resting serum MOTS-c correlated with jump power and force and with muscle mass, but not with peak oxygen uptake.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10573682/","grade":"human-obs","grade_label":"Human observational","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-064","text":"In 30 people randomized to endurance exercise, resistance exercise or control, acute endurance exercise significantly raised circulating humanin while MOTS-c showed only a trend toward increase.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12854548/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-065","text":"In a 16-week randomized exercise trial in breast cancer survivors, plasma MOTS-c rose significantly in non-Hispanic White participants but not in Hispanic participants.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8376922/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-066","text":"In 19 active men randomized to heat or sham during two weeks of ankle immobilization, repeated heat exposure raised circulating MOTS-c, while immobilization itself did not change mitokine levels.","source_url":"https://europepmc.org/article/MED/40674654","grade":"human-rct","grade_label":"Human RCT","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-067","text":"In a randomized trial of metformin added to neoadjuvant therapy for HER2-positive breast cancer, 24 weeks of treatment produced no significant change in circulating MOTS-c.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10008497/","grade":"human-rct","grade_label":"Human RCT","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/studies"]},{"id":"clm-068","text":"The exercise-mimetic label originates in the research literature itself, where MOTS-c is described as a mitochondrially encoded exercise-mimetic peptide and as having exercise mimetic activity.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10008497/","grade":"review","grade_label":"Review or guideline","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-069","text":"FDA considers MOTS-c free base and MOTS-c acetate not well-characterized, citing inconsistent naming conventions and the absence of impurity, aggregate, endotoxin and bioburden control data in public literature and in the certificates of analysis it reviewed.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/decision_aid","https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-070","text":"FDA states it cannot rule out immunogenicity from peptide-related impurities and aggregates, and notes subcutaneous administration is generally associated with increased immunogenicity compared with intravenous administration.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-071","text":"The only stability information FDA identified came from supplier pages: lyophilized MOTS-c stored below -20 degrees C desiccated and protected from light, with reconstituted solution kept at about 4 degrees C for 2 to 7 days or below -18 degrees C for later use.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph","https://motscco.com/tooldata"]},{"id":"clm-072","text":"MOTS-c is marketed online for uses including regulating mitochondrial energy, promoting metabolic homeostasis, improving glucose regulation, promoting weight loss and improving physical performance, and FDA notes it is unclear whether compounded products are involved in all of these instances.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-073","text":"There is no United States Pharmacopeia or National Formulary monograph for MOTS-c free base or its acetate salt, and searches of the European and Japanese Pharmacopoeias and the European Medicines Agency found no listings or authorized products.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-074","text":"FDA notes there are FDA-approved drug products for weight reduction in obesity and for treatment of osteoporosis, the two uses on its MOTS-c meeting agenda.","source_url":"https://www.fda.gov/media/193347/download","grade":"regulatory","grade_label":"Regulatory record","used_on":["https://motscco.com/decision_aid","https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-075","text":"MOTS-c belongs to a family of mitochondrial-derived peptides: eight have been identified, with MOTS-c encoded in the 12S ribosomal RNA gene (MT-RNR1) and humanin plus six small humanin-like peptides encoded in the 16S ribosomal RNA gene.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7750512/","grade":"review","grade_label":"Review or guideline","used_on":["https://motscco.com/comparison","https://motscco.com/entity","https://motscco.com/faq","https://motscco.com/monograph"]},{"id":"clm-076","text":"Reviews of the field state that whether the metaboloprotective properties of mitochondrial-derived peptides can be turned into therapies for metabolic disease remains to be fully determined.","source_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7750512/","grade":"review","grade_label":"Review or guideline","used_on":["https://motscco.com/comparison","https://motscco.com/faq","https://motscco.com/limits","https://motscco.com/monograph"]},{"id":"clm-090","text":"This monograph's study table contains 34 rows.","source_url":"https://motscco.com/copy","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://motscco.com/copy","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-091","text":"Zero rows in this monograph's study table report administering MOTS-c to human participants with published results.","source_url":"https://motscco.com/copy","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://motscco.com/copy","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-092","text":"This pack cites 42 sources, all peer-reviewed, government or trial-registry records.","source_url":"https://motscco.com/copy","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://motscco.com/copy","https://motscco.com","https://motscco.com/monograph"]},{"id":"clm-093","text":"This monograph's study table includes rows for four distinct things people call MOTS-c evidence: administered MOTS-c, measured endogenous MOTS-c, MOTS-c genotype, and the CB4211 analog.","source_url":"https://motscco.com/copy","grade":"internal-measurement","grade_label":"Internal measurement","used_on":["https://motscco.com/copy","https://motscco.com","https://motscco.com/monograph"]}]}