# MOTS-c: full monograph (MOTS-c Co)
> Source page: https://motscco.com/monograph

Status: Compounded, not FDA-approved
Disclosure: MOTS-c is not FDA approved. FDA reports no human exposure data for it by any route, and it is sold only for research use with no established human efficacy.

## Key facts
- Status: Compounded, not FDA-approved
- Human plasma half-life: Never measured (source: https://www.fda.gov/media/193347/download)
- Animal pharmacokinetics: No in vivo PK or toxicokinetic study identified (source: https://www.fda.gov/media/193347/download)
- Bioavailability (any route): Never characterized (source: https://www.fda.gov/media/193347/download)
- Stability in human blood (in vitro): Cut to MOTS-c(2-16) through (5-16) within 15 minutes at 5 mcg/mL (source: https://www.fda.gov/media/193347/download)
- Active concentrations after dosing: FDA: remains to be determined (source: https://www.fda.gov/media/193347/download)
- Dose-response in animals: Not established in vivo, per FDA review (source: https://www.fda.gov/media/193347/download)
- Detection in sport: Validated plasma LC-MS method published 2019 (source: https://europepmc.org/article/MED/30394592)
- Class: Mitochondrial-derived peptide (16 amino acids, encoded in MT-RNR1) (source: https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/)
- Formula / weight: C101H152N28O22S2 / 2174.6 g/mol (free base) (source: https://pubchem.ncbi.nlm.nih.gov/compound/146675088)
- Sequence: MRWQEMGYIFYPRKLR (source: https://pubchem.ncbi.nlm.nih.gov/compound/146675088)
- FDA approval: None, any form (Drugs@FDA: no record for MOTS-c) (source: https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22mots-c%22&limit=3)
- Human exposure data: FDA has not identified any, by any route (source: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks)
- Published human dosing studies: None found by FDA or by our own search of 248 PubMed records (source: https://www.fda.gov/media/193347/download)
- Registered human trials of MOTS-c: 1 (Phase 2a, recruiting, no results posted) (source: https://clinicaltrials.gov/study/NCT07505745)
- Human half-life: Never measured, in any species (source: https://www.fda.gov/media/193347/download)
- Animal toxicity package: No acute, repeat-dose, genotoxicity, reproductive or carcinogenicity studies identified (source: https://www.fda.gov/media/193347/download)
- July 2026 PCAC: FDA proposed MOTS-c free base and acetate NOT be added to the 503A list (source: https://www.fda.gov/media/193342/download)
- WADA 2026: Named under S4.4.1 (AMPK activators); prohibited at all times (source: https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf)
- Analog with human data: CB4211, Phase 1a/1b completed 2021, no results posted (source: https://pmc.ncbi.nlm.nih.gov/articles/PMC9057581/)

## What is MOTS-c?
MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. It is a 16-amino-acid peptide (sequence H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH, molecular weight 2174.6 g/mol) encoded not in the cell nucleus but inside the mitochondrial genome, within the 12S ribosomal RNA gene MT-RNR1  [1,41]. It belongs to a family of eight known mitochondrial-derived peptides; MOTS-c is the one encoded by the 12S gene, while humanin and the six small humanin-like peptides come from the 16S gene  [33].
The biology is genuinely interesting and the discovery is real. Researchers have measured MOTS-c circulating in humans and rodents and expressed in skeletal muscle, heart and brain, and the peptide appears to be conserved across species  [35]. The research literature itself, not only marketing copy, calls it an exercise mimetic  [31,29].
This site exists because of a gap between two things that are both true. The discovery science is strong and continuing. The record of giving MOTS-c to human beings and measuring what happens is, as of this page's verification date, empty of published results. Every row in the evidence table below names the species it came from and, just as importantly, which molecule was actually studied: MOTS-c given as a drug, MOTS-c measured as a natural hormone, a MOTS-c genotype, or a chemically different analog.

## Key facts at a glance
The fact chips beside this section carry their evidence grade and link to the source that establishes each one. Three of them record documented absences rather than findings, because in this compound's file the absences are the most decision-relevant facts available.

## Regulatory status: not approved, no human exposure data, proposed for exclusion
MOTS-c is not FDA approved. FDA reports no human exposure data for it by any route, and it is sold only for research use with no established human efficacy. A query of FDA's approved-drug database for MOTS-c as an active ingredient returns no matches  [38], and there is no United States Pharmacopeia or National Formulary monograph for either the free base or the acetate salt  [35].
FDA's compounding safety-risks page states the position in its own words: compounded drugs containing MOTS-c "may pose significant risk for immunogenicity for certain routes of administration", the agency "has not identified any human exposure data on drug products containing MOTs-C administered via any route of administration", and it "lacks important information regarding any safety issues raised by MOTs-C, including whether it would cause harm if administered to humans"  [34]. That is the regulatory photograph of this compound: not a warning about known harms, a statement that nobody has documented what happens.
On 23 July 2026 FDA's Pharmacy Compounding Advisory Committee reviewed MOTS-c-related bulk drug substances, listed on the meeting agenda against the uses obesity and osteoporosis  [37]. The nomination, from Wells Pharmacy Network, had been withdrawn; FDA proceeded on its own initiative  [35]. FDA's briefing document proposed that MOTS-c (free base) and MOTS-c acetate both NOT be included on the 503A Bulks List  [36], and its 44-page substance evaluation concluded that "a balancing of the criteria weighs against MOTS-c free base or MOTS-c acetate being placed on that list"  [35].
Two pieces of precision matter here. First, committee advice is non-binding and rulemaking is pending, and even a substance placed on that list would be eligible for pharmacy compounding, not FDA approved  [36]. Second, as of this page's verification date FDA's meeting page carried agenda and briefing materials but no posted vote tally or minutes, so this site does not tell you how the committee voted  [37]. Trade press reported outcomes; we cite FDA documents, and FDA has not published that record yet.
In sport, the 2026 WADA Prohibited List names MOTS-c by its full name under section S4.4.1, activators of AMP-activated protein kinase, inside the hormone and metabolic modulators class, which is prohibited at all times  [42]. FDA notes the same listing reaching athletes through the Global Drug Reference Online database  [35]. There are FDA-approved drug products for weight reduction in obesity and for osteoporosis, the two uses on FDA's MOTS-c agenda  [35].

## Mechanism: what MOTS-c does in cells, and what that does not prove
The proposed mechanism is specific and testable. In the discovery work, MOTS-c inhibited the folate cycle and the de novo purine synthesis tethered to it, causing accumulation of AICAR, an established activator of AMP-activated protein kinase, with skeletal muscle as the apparent target organ  [1]. A 2018 paper showed MOTS-c translocating into the nucleus under metabolic stress and regulating nuclear genes in an AMPK-dependent way, interacting with antioxidant-response transcription factors including NRF2  [2]. A 2024 study identified casein kinase 2 as a direct binding target, with muscle effects blunted when CK2 was suppressed  [4].
That is real mechanistic work, and it is why the compound is taken seriously in the laboratory. It is also why FDA's assessment of the same literature is worth quoting rather than paraphrasing: nonclinical pharmacology of MOTS-c "have been limited to in-vivo and in-vitro rodent models and have not evaluated the dose-response relationships for the effects of MOTS-c in vivo", and "the molecular target(s) through which MOTS-c acts remains unknown. As such, it is difficult to predict which organs might be targeted and affected by MOTS-c"  [35].
A mechanism explains how something could work. It is not evidence that it does work in people at any particular dose.

## The evidence map: four different things people call MOTS-c evidence
Almost every argument made for buying MOTS-c draws on one of four literatures. They are not interchangeable, and the study table below labels every row with which one it belongs to.
One: MOTS-c administered as a drug. Every published study in this category is in mice, rats or cells. This is where the impressive results live, including the lifespan and treadmill data.
Two: endogenous MOTS-c measured in human blood or muscle. These are real human studies, but nobody was given anything; the peptide was measured as a naturally occurring hormone, and the findings point in different directions depending on the population.
Three: MOTS-c genotype. The K14Q association studies are human genetics in large Japanese and Korean cohorts. They can show that carrying a less active version of the peptide travels with a health outcome. They cannot show that injecting the peptide changes that outcome.
Four: CB4211, a chemically different analog developed from licensed MOTS-c intellectual property, which did complete a Phase 1 program in humans  [32,40].
Set against those four literatures is the finding FDA reported after its own search, in its own words: "We performed our own search of published medical literature and did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects"  [35]. Our independent check agrees: 248 records mention MOTS-c in their title or abstract on PubMed, and none of them reports giving it to human participants  [32]. Reviewers in the field put the state of play plainly: whether these peptides can be harnessed into therapies "remains to be fully determined"  [33].

## What happened when animals were given MOTS-c
This is the strongest part of the file, and it deserves to be stated at full strength before it is qualified. In the 2015 discovery paper, mice on a 60 percent fat diet given 0.5 mg/kg/day of MOTS-c for eight weeks weighed about 20 percent less than vehicle-treated mice, with higher energy expenditure and less liver fat; at 5 mg/kg/day, clamped mice needed about 30 percent more glucose to stay euglycemic, and seven days of treatment restored the insulin sensitivity of 12-month-old soleus muscle to that of 3-month-old muscle  [35,1].
The 2021 Nature Communications study is the one behind most exercise-mimetic marketing. A single 5 mg/kg dose improved treadmill performance in young, middle-aged and old mice, and intermittent dosing started at 23.5 months of age, very late in a mouse life, raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days  [35,3].
Elsewhere in rodents: 5 mg/kg daily for 12 weeks reduced ovariectomy-induced bone loss on micro-CT  [5]; local injection reduced particle-induced calvarial osteolysis  [7]; 5 mg/kg/day for four weeks attenuated vascular calcification and myocardial remodeling in rats  [9]; treatment improved cold tolerance and browning of white fat  [8]; 15 mg/kg/day held immobilization muscle loss to about 5 percent instead of about 15 percent  [11]; and 15 mg/kg twice daily preserved quadriceps mass in cancer cachexia by 12 percent while failing to prevent overall weight or fat loss  [12].
Two honest qualifications belong beside all of it. The doses are large by peptide standards and were given intraperitoneally in most studies, a route nobody uses at home. And FDA's reviewers noted that this body of work has never established a dose-response relationship in vivo  [35], which is exactly the information a person would need to reason from a mouse dose to anything else.

## Human evidence: what exists, and what does not
No published study has given MOTS-c to a human being and reported the result. FDA searched for one and did not find it  [35]; so did we  [32]. FDA also reports that outsourcing facilities filed no reports of compounding MOTS-c products between January 2017 and December 2025  [35].
One registered trial would change this page if it reports. NCT07505745 is a Phase 2a randomized, 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 and recruiting at Peking University Shenzhen Hospital since February 2026, with insulin sensitivity by Matsuda index and treatment-emergent adverse events as its primary endpoints  [39]. It has posted no results, and its public record does not state the dose  [39]. A registered trial is a plan, not a finding.
What does exist in humans is measurement of the peptide people already make. Those studies are real and they disagree in an interesting way. Plasma MOTS-c was no different between lean and obese adults in one small study but tracked insulin resistance in the lean group  [20]; it was lower in obese boys  [21]; it was higher in adults with obesity at the Mayo Clinic and did not budge six months after bariatric surgery  [26]; and a meta-analysis of 602 participants found it decreased in diabetes yet increased in obesity, which the authors describe as opposite results  [27]. In healthy aging men, blood levels fell with age while muscle expression rose  [22].
Read together, those studies suggest MOTS-c behaves like a stress-responsive signal rather than a simple fuel gauge that is low in illness and high in health. None of them tested whether adding more of it helps.

## The K14Q polymorphism: what association genetics can and cannot show
The longevity story attached to MOTS-c starts with genetics, not dosing. An East-Asian-specific mitochondrial variant, m.1382A>C, swaps the 14th amino acid from lysine to glutamine, producing a variant called K14Q that has less biological activity  [17,18].
The cohorts are large and the findings are specific. A meta-analysis of three Japanese cohorts totalling 27,527 people found men, but not women, with 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  [17]. In 211 Japanese adults the C allele tracked a higher proportion of fast-twitch fibers, and across 721 athletes and 873 controls it was most common in sprint and power athletes (6.5 percent), then controls (5.1 percent), then endurance athletes (2.9 percent)  [18]. In 683 older Korean adults, men with the C allele had more muscle mass and stronger grip  [19].
Here is the limit of what that design can establish. Association genetics compares people who inherited different versions of a peptide across a lifetime. It can support the claim that MOTS-c activity matters for human metabolism. It cannot establish that injecting MOTS-c into an adult produces the outcome associated with the more active genotype, any more than a gene associated with height means an injection makes an adult taller. The same 2021 paper made the distinction concrete inside one study: male mice given MOTS-c lost weight and improved glucose tolerance, mice given the K14Q variant peptide did not, and female mice were unaffected by either  [17].
The Japanese-longevity framing traces back to a two-page 2015 hypothesis article that proposed the polymorphism "may be among the putative biological mechanisms explaining the high longevity of Japanese people" and said in the same sentence that more research is needed  [16]. That is a hypothesis paper doing its job, and it is not a finding about supplementation.

## CB4211: the human trial that was not a MOTS-c trial
Sales pages sometimes point to a completed Phase 1 program as evidence that MOTS-c has been through human trials. That program tested CB4211, which a peer-reviewed review describes as "the MOTS-c analog CB4211", developed after MOTS-c intellectual property was licensed by CohBar and used to build potent analogs  [32]. An analog is a different molecule designed to behave similarly. It is not the peptide in a research vial.
The trial itself is a real, well-designed study: NCT03998514, a three-part Phase 1a/1b randomized, double-blind, placebo-controlled evaluation of single and multiple ascending subcutaneous doses in healthy non-obese subjects and in subjects with nonalcoholic fatty liver disease, 88 participants, completed on 19 April 2021  [40].
Two facts finish the story. The registry record has no results posted, and a PubMed search for CB4211 returns zero records, so that human dataset has never been published in the peer-reviewed literature  [40,32]. And the registry record never mentions MOTS-c at all: its condition is nonalcoholic fatty liver disease and its interventions are labeled only as CB4211 dose levels and placebo  [40].
So the sentence "MOTS-c has been in human trials" fails twice over: the trial tested a different molecule, and it reported nothing. FDA classifies even the free base and the acetate salt of MOTS-c as distinct substances with potentially different safety and efficacy profiles  [35]; an analog is further away still.

## Pharmacokinetics: an absence, plus one test-tube clue
There is no pharmacokinetic profile for MOTS-c in any species. FDA states it "did not identify in-vivo pharmacokinetic or toxicokinetic studies of MOTS-c", and separately that no clinical study provided pharmacokinetic data  [35]. No half-life, no bioavailability, no dose-exposure curve exists to cite, in humans or in animals.
The one relevant experiment is a test-tube study built for anti-doping purposes. MOTS-c at 5 micrograms per mL was incubated in human whole blood at 37 degrees C, and within 15 minutes mass spectrometry showed it cut into shorter fragments: MOTS-c(2-16), (3-16), (4-16) and (5-16)  [35,15]. Degradation was described as rapid and not requiring long incubation.
FDA draws the honest conclusion from that observation rather than an alarming one: "It remains to be determined whether exogenous administration of MOTS-c to humans can generate pharmacologically active concentrations of the peptide over time"  [35]. Anyone quoting a half-life for MOTS-c, in hours or in minutes, is quoting something that has not been measured.

## Forms and routes: what is sold versus what was studied
MOTS-c is sold as a lyophilized powder in vials, typically labeled 5 mg or 10 mg, for reconstitution and subcutaneous injection. That matches what was nominated to FDA: "5 mg and 10 mg for subcutaneous (SC) injection"  [35].
The published animal work mostly used intraperitoneal injection, and one bone study used local injection into the treated area  [7]. No published study establishes what subcutaneous dosing does in any species, and FDA notes subcutaneous administration is generally associated with greater immunogenicity risk than intravenous  [35].
Oral, nasal and topical MOTS-c products appear online. There is no published human or animal study of any of those routes, and the peptide's rapid breakdown in blood makes any oral claim particularly unsupported  [15].

## Doses used in research (there is no established human dose)
There is no established human dose of MOTS-c. No human dose-finding study has been published, the one registered trial does not state its dose in the public record, and FDA reports that the animal literature never established a dose-response relationship in vivo  [39,35].
What does exist are the doses used in animals, which our study-dose explorer lists with species attached: 0.5 mg/kg/day and 5 mg/kg/day intraperitoneally in the discovery mouse work  [1], 5 mg/kg acutely and 15 mg/kg three times weekly in the lifespan study  [3], 5 mg/kg/day for 12 weeks in the ovariectomy bone model  [5], 5 mg/kg/day for four weeks in the rat vascular model  [9], 15 mg/kg/day in the immobilization model  [11] and 15 mg/kg twice daily in cachexia  [12].
Those numbers are mouse and rat doses. Converting them into a human dose requires pharmacokinetic data that does not exist for this peptide in any species, which is why this site publishes no conversion and no suggested amount.

## Safety: the questions people actually ask
Is MOTS-c known to be dangerous? No. Is it known to be safe? Also no, and that is the accurate answer. FDA states plainly: "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. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown"  [35].
What about side-effect reports? FDA searched its adverse event reporting system for MOTS-c through March 2025 and the searches "retrieved no reports"  [35]. That is weaker reassurance than it sounds: FDA notes in the same document that compounders under section 503A generally do not report adverse events to the agency, so an empty database mostly reflects a reporting pathway that barely exists here  [35].
What about animal toxicity studies? None were found. FDA reports identifying no acute toxicity, repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity, or carcinogenicity studies of MOTS-c free base or acetate  [35]. The usual preclinical safety package for a drug entering humans does not exist for this peptide.
What is the specific risk FDA names? Immunogenicity. Compounded MOTS-c "may pose significant risk for immunogenicity for certain routes of administration and may have complexities with regard to peptide-related impurities and API characterization"  [34], and FDA cannot rule out immune responses driven by impurities and peptide aggregates because the quality-control data needed to do so were not found in public literature or in the certificates of analysis reviewed  [35].
Who has not been studied? Everyone. With zero human administration studies published, there is no data on pregnancy, breastfeeding, children, older adults, or people with kidney, liver, cardiac or oncologic disease.
Is it a doping risk? Yes, unambiguously. MOTS-c is named on the 2026 WADA Prohibited List under S4.4.1, and a validated mass-spectrometry method for detecting it in plasma has existed since 2019  [42,15].

## Interactions and contraindications: an empty file, stated as empty
No interaction study of MOTS-c with any medication has been published in any species. No contraindication list exists because contraindications are derived from clinical experience that has not been collected.
One indirect signal is worth stating precisely. In a randomized trial where metformin was added to breast cancer treatment, circulating MOTS-c did not change significantly  [31]. That is a study of metformin's effect on natural MOTS-c levels, not a study of a drug interaction with injected MOTS-c, and it should not be quoted as one.
Anyone considering this compound while taking prescription medication is reasoning without data, and the right place to take that problem is a clinician who can see the whole medication list.

## Vials, certificates and what quality control is missing
FDA's chemistry review of MOTS-c is the most useful document in existence for anyone evaluating a vial, because it lists exactly what a certificate of analysis usually leaves out. FDA found no impurity limits, no aggregate testing, no microbial bioburden and no bacterial endotoxin testing in the certificates it reviewed or in the public literature, and concluded both the free base and the acetate salt are "not well-characterized"  [35]. Endotoxin testing is described as a critical quality attribute for an injectable product.
Naming is its own hazard. FDA notes that MOTS-c is a common name, not a United States Adopted Name, and that it has encountered "multiple salts, and derivatives, including different active moieties, sold commercially under the same common name", a situation in which someone may be dosed with a different substance than intended  [35]. In the nomination FDA reviewed, the certificate of analysis named one substance in its title and a different one by CAS number.
The storage guidance circulating online traces to supplier pages, not stability studies: lyophilized peptide below -20 degrees C, desiccated and protected from light; reconstituted solution at about 4 degrees C for 2 to 7 days or below -18 degrees C for longer  [35]. Those are handling conventions, and no validated shelf life for a finished MOTS-c product exists.

## How MOTS-c reaches buyers, stated without a pitch
MOTS-c is sold online as a research chemical and appears in some clinic offerings, including combination infusions. FDA's own survey of the market records claims that it regulates mitochondrial energy, promotes metabolic homeostasis, improves glucose regulation, promotes weight loss and improves physical performance, and notes it is unclear whether compounded products are involved in all of those instances  [35].
There is no approved MOTS-c product to buy anywhere  [38], no pharmacopeial monograph in the United States, Europe or Japan, and no product authorized by the European Medicines Agency  [35]. Outsourcing facilities reported no MOTS-c compounding to FDA across a nine-year window  [35].
This site sells nothing, takes no affiliate commissions and links to no vendor.

## Frequently asked questions
The questions below are the ones this compound actually generates. Each answer states its evidence grade in the first sentence.

## References and citation manifest
Every citation below was fetched and verified during pack production. The machine-readable citation manifest carries the same list with source types, identifiers and verification dates.

## Study results
| Study | Species/model | n | Duration | Outcome | Effect size |
| --- | --- | --- | --- | --- | --- |
| S1 (https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/) | mouse (Diet-induced obesity and insulin resistance; hyperinsulinemic-euglycemic clamp; ex vivo soleus) | Group sizes not stated in abstract | 8 weeks; 7 days | Prevented diet-induced obesity and age- and diet-dependent insulin resistance; treated mice weighed about 20 percent less than vehicle; glucose infusion rate about 30 percent higher; insulin sensitivity of 12-month-old soleus restored to 3-month-old levels | About 20 percent lower body weight; about 30 percent higher glucose infusion rate |
| S2 (https://pmc.ncbi.nlm.nih.gov/articles/PMC7817689/) | mouse (Treadmill performance in young, middle-aged and old mice; late-life intermittent dosing survival study) | Group sizes not stated in abstract | Acute to end of life | Enhanced treadmill performance at all three ages; late-life intermittent dosing raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days; in humans the same paper reports exercise induces endogenous MOTS-c | Median lifespan 970 vs 912 days; maximal 1120 vs 1047 days |
| S3 (https://pmc.ncbi.nlm.nih.gov/articles/PMC6185997/) | in vitro (mammalian cells) (Glucose restriction and metabolic stress in cultured cells; nuclear translocation assays) | Cell systems | Hours to 72 hours | MOTS-c translocated to the nucleus and regulated nuclear gene expression in an AMPK-dependent manner, interacting with antioxidant-response-element transcription factors including NRF2 | Descriptive; no organism-level endpoint |
| S4 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11570452/) | mouse and human (Cell-free binding assays; mouse muscle atrophy and glucose uptake; human cohort genotype analysis) | Cell-free plus mouse groups; human cohort sizes not stated in abstract | Not stated in abstract | CK2 identified as a direct functional target: MOTS-c bound and activated CK2, prevented muscle atrophy and enhanced muscle glucose uptake in mice, all blunted by CK2 suppression; the K14Q variant bound CK2 poorly and produced no effect | Tissue-specific: CK2 activated in muscle, suppressed in fat |
| S5 (https://europepmc.org/article/MED/27237975) | mouse (Ovariectomy-induced bone loss with micro-CT; RANKL-induced osteoclast differentiation) | Group sizes not stated in abstract | 12 weeks | Alleviated bone loss on micro-CT; inhibited RANKL-induced osteoclast differentiation; effect partially abrogated by the AMPK inhibitor compound C | Qualitative micro-CT improvement; no fracture endpoint |
| S6 (https://europepmc.org/article/MED/31369811) | mouse (Ultra-high molecular weight polyethylene particle calvaria model; primary bone marrow macrophages) | Group sizes not stated in abstract | 7 days | Reduced bone erosion and inflammation; raised the osteoprotegerin to RANKL ratio in osteocytes; blunted STAT1 and NF-kB phosphorylation in macrophages | Descriptive histomorphometry |
| S7 (https://europepmc.org/article/MED/30468456) | in vitro (rat cells) (Rat bone marrow mesenchymal stem cells differentiated in vitro) | Cell cultures | 7 days | Increased ALP, RUNX2 and osteocalcin expression and calcified nodule formation; effect dependent on TGF-beta/Smad signaling | Gene and staining endpoints only |
| S8 (https://europepmc.org/article/MED/31694019) | rat (Vitamin D3 plus nicotine-induced vascular calcification in Sprague-Dawley rats with echocardiography) | Group sizes not stated in abstract | 4 weeks | Attenuated aortic calcium deposition, blood pressure rise and myocardial remodeling; prevented the fall in phosphorylated AMPK and the rise in AT1 and endothelin B receptors | Descriptive; no clinical outcome |
| S9 (https://pmc.ncbi.nlm.nih.gov/articles/PMC6567243/) | mouse (Cold exposure model with brown and white adipose tissue analysis) | Group sizes not stated in abstract | Cold exposure protocol | Enhanced cold tolerance, upregulated brown adipose thermogenic genes and promoted white fat browning, apparently via ERK signaling; serum MOTS-c fell after cold stress | Gene expression and tolerance endpoints |
| S10 (https://pmc.ncbi.nlm.nih.gov/articles/PMC8238132/) | mouse and human (Diet-induced obese mice plus palmitic-acid-treated C2C12 myotubes; human plasma correlation) | Not stated in abstract | Not stated in abstract | MOTS-c prevented myotube atrophy in vitro and lowered plasma myostatin in obese mice; in human samples plasma MOTS-c was inversely correlated with myostatin | Correlational in humans; mechanistic in mice |
| S11 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11196098/) | mouse (Casting-induced immobilization in 10-week-old male C57BL/6J mice, randomized to three groups) | Three groups, sizes not stated in abstract | 8 days | Immobilization reduced muscle mass by about 15 percent; MOTS-c limited the loss to about 5 percent, normalized AKT and FOXO phosphorylation and lowered circulating IL-1beta, IL-6, CXCL1 and MCP-1 | 5 percent vs 15 percent muscle mass loss |
| S12 (https://pmc.ncbi.nlm.nih.gov/articles/PMC13243040/) | mouse (Colon-26 carcinoma cachexia model plus differentiated myotubes) | Group sizes not stated in abstract | Daily to euthanasia | Preserved quadriceps mass (+12 percent vs vehicle) and attenuated Atrogin-1 and MuRF1 induction, but did not prevent total body weight or fat loss | +12 percent quadriceps weight; body weight loss unchanged |
| S13 (https://pmc.ncbi.nlm.nih.gov/articles/PMC13394035/) | rat (High-fat-diet plus streptozotocin type 2 diabetes model with cardiac immunohistochemistry) | Group sizes not stated in abstract | Not stated in abstract | Reduced fasting glucose and C-reactive protein and lowered NLRP3, ASC and cleaved caspase-1 in left ventricular tissue | Biomarker and histology endpoints |
| S14 (https://europepmc.org/article/MED/40472776) | mouse, in vitro and human (House dust mite asthma model in wild-type and Nrf2-knockout mice; BEAS-2B human cells; patient serum) | Not stated in abstract | 2 hours pretreatment plus 24 hours in cells | Serum MOTS-c was lower in patients with asthma than healthy volunteers; exogenous MOTS-c reduced lung injury, inflammation and oxidative stress in mice through Nrf2 | Descriptive |
| S-knoop (https://europepmc.org/article/MED/30394592) | in vitro (human whole blood) (MOTS-c incubated in human whole blood at 37 degrees C; LC-MS doping-control method development) | Ex vivo blood samples | 15 or 60 minutes | Rapid proteolytic hydrolysis to MOTS-c(2-16), (3-16), (4-16) and (5-16); FDA cites this as the only pharmacokinetic-related study it identified and notes it remains unknown whether dosing humans can produce active concentrations over time | Degradation detectable within 15 minutes |
| S15 (https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/) | human (Meta-analysis of three Japanese cohorts (J-MICC, MEC, TMM) genotyped for m.1382A>C) | 27,527 | Cross-sectional cohorts | Men carrying the C allele had higher prevalence of type 2 diabetes; women did not; in J-MICC the association appeared only in men in the lowest physical-activity tertile | Association only; no effect estimate reproduced here beyond the abstract's direction |
| S16 (https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/) | mouse (High-fat-fed male and female mice injected with MOTS-c or K14Q-MOTS-c) | Group sizes not stated in abstract | Not stated in abstract | MOTS-c reduced weight and improved glucose tolerance in male mice; the K14Q variant did not; female mice were unaffected by either | Null result for the variant peptide |
| S17 (https://pmc.ncbi.nlm.nih.gov/articles/PMC8741734/) | human (Muscle fiber composition in 211 Japanese adults; strength in 86 men; allele frequency in 721 athletes and 873 controls) | 211 plus 86 plus 1,594 | Cross-sectional | C-allele carriers had a higher proportion of fast-twitch MHC-IIx and men had higher peak leg torques; C allele was more frequent in sprint and power athletes (6.5 percent) than controls (5.1 percent) or endurance athletes (2.9 percent) | 6.5 vs 5.1 vs 2.9 percent allele frequency |
| S18 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11504729/) | human (Community-dwelling Korean adults aged 65 and older, genotyped by real-time PCR) | 683 (345 men, 338 women) | Cross-sectional | Men with the C allele had higher appendicular skeletal muscle mass, lean mass and handgrip strength; no significant differences among women | Handgrip 35.6 vs 30.9 kg (right) in men |
| S19 (https://pmc.ncbi.nlm.nih.gov/articles/PMC4693465/) | human (Two-page hypothesis and commentary article about m.1382A>C and Japanese longevity) | No original cohort | n/a | Proposed that the Northeast-Asian-specific m.1382A>C polymorphism may be among putative mechanisms behind Japanese longevity, stating explicitly that more research is needed | Hypothesis only; no effect estimate |
| S20 (https://europepmc.org/article/MED/29593067) | human (Cross-sectional comparison of lean and obese adults with Matsuda and HOMA indexes) | 20 (10 per group) | Single timepoint | Plasma MOTS-c did not differ between lean and obese (0.48 vs 0.52 ng/mL, p=0.60) but correlated with insulin-resistance indexes mainly in lean participants | r=0.53 with HOMA; r=-0.46 with Matsuda |
| S21 (https://europepmc.org/article/MED/29691953) | human (Case-control study of obese and control children and adolescents) | 97 (40 obese, 57 control) | Single timepoint | MOTS-c lower in the obese group overall and in boys specifically; not different in girls; inversely correlated with BMI, waist, fasting insulin, HOMA-IR and HbA1c in boys | 472.61 vs 561.64 ng/mL |
| S22 (https://pmc.ncbi.nlm.nih.gov/articles/PMC12807633/) | human (Lean controls versus adults with obesity before bariatric surgery, with 6-month follow-up in a subset) | 54 (22 lean, 32 obese); 10 followed after surgery | Baseline plus 6 months | MOTS-c higher in obesity (273 vs 223 pg/mL, p<0.01) and unchanged after significant weight loss; adipose tissue MOTS-c did not differ or correlate with circulating levels | 273 vs 223 pg/mL; post-surgery p=0.913 |
| S23 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11331736/) | human (Systematic review and meta-analysis of six case-control and one cross-sectional study) | 602 participants across 11 groups | Pooled cross-sectional | Pooled MOTS-c was lower in diabetes (SMD -0.89) and higher in obesity (SMD 0.51), described by the authors as opposite results after subgroup analysis | SMD -0.89 (diabetes); SMD 0.51 (obesity) |
| S24 (https://pmc.ncbi.nlm.nih.gov/articles/PMC7138593/) | human (Healthy men in three age bands with plasma and muscle biopsy measurement) | Three age groups, sizes not stated in abstract | Cross-sectional | Circulating MOTS-c fell with age while muscle MOTS-c expression was about 1.5-fold higher in middle-aged and older men; muscle expression tracked slow-type fiber markers | About 1.5-fold higher muscle expression |
| S25 (https://europepmc.org/article/MED/34419510) | human (Chinese and European adults without diabetes with DEXA and MRI or spectroscopy) | 125 Chinese plus 34 European women | Cross-sectional | Plasma MOTS-c elevated in metabolic syndrome and associated with waist circumference and liver fat; authors interpret it as a hepatic-stress signal | 315 pg/mL mean in the Chinese cohort |
| S26 (https://europepmc.org/article/MED/32052315) | human (Type 2 diabetes after coronary revascularization, 2-year follow-up plus external validation cohort) | 121 plus 90 validation | 2 years | MOTS-c below 167 ng/mL predicted major adverse cardiac events (relative risk 3.8) alongside high on-clopidogrel platelet reactivity | Relative risk 3.8 |
| S27 (https://pmc.ncbi.nlm.nih.gov/articles/PMC10573682/) | human (Physically active volunteers with countermovement jump tests and cardiopulmonary exercise testing) | 20 (17 male, 3 female) | Single timepoint | Resting serum MOTS-c correlated with jump power and force and with muscle mass, but not with peak oxygen uptake | No correlation with peak VO2 |
| S28 (https://pmc.ncbi.nlm.nih.gov/articles/PMC12854548/) | human (Randomized allocation to acute endurance exercise, resistance exercise or control with biopsies and blood sampling) | 30 (10 per arm) | Pre, 30 min and 3 h post | Humanin rose significantly after endurance exercise; MOTS-c showed only a trend toward increase; plasma levels were unrelated to fitness measures | MOTS-c change not statistically significant |
| S29 (https://pmc.ncbi.nlm.nih.gov/articles/PMC8376922/) | human (16-week aerobic and resistance exercise versus standard care in breast cancer survivors) | 49 (25 Hispanic, 24 non-Hispanic White) | 16 weeks | Plasma MOTS-c rose significantly in non-Hispanic White participants but not in Hispanic participants, where it was associated with reduced fat mass and HOMA-IR | Significant in one ethnic subgroup only |
| S30 (https://europepmc.org/article/MED/40674654) | human (Randomized heat versus sham during two weeks of ankle immobilization in active men) | 19 (9 heat, 10 sham) | 2 weeks | Repeated heat raised circulating MOTS-c (p=0.033) while immobilization alone did not change mitokine levels; muscle thickness and cross-sectional area still fell | p=0.033 for circulating MOTS-c |
| S31 (https://pmc.ncbi.nlm.nih.gov/articles/PMC10008497/) | human (Metformin added to neoadjuvant chemotherapy and trastuzumab in HER2-positive breast cancer) | Paired sera from the METTEN randomized study | 24 weeks | No significant change in circulating MOTS-c with or without metformin, and no significant difference by pathological complete response | Null on the MOTS-c endpoint |
| S-reg-motsc (https://clinicaltrials.gov/study/NCT07505745) | human (Phase 2a randomized, double-blind, placebo-controlled, quadruple-masked, parallel-group study) | 120 estimated | 12 weeks treatment, 16 weeks safety follow-up | Recruiting since February 2026 at Peking University Shenzhen Hospital; primary endpoints are change in Matsuda index and treatment-emergent adverse events; no results posted | No results posted |
| S-reg-cb4211 (https://clinicaltrials.gov/study/NCT03998514) | human (Phase 1a/1b three-part randomized, double-blind, placebo-controlled single and multiple ascending dose study) | 88 actual | Completed 19 April 2021 | Safety, tolerability, pharmacokinetics and pharmacodynamics in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease; sponsor CohBar; no results posted and no PubMed publication | No results posted |

## What we do not know yet
What is unknown about MOTS-c is larger than what is known, and this section is the honest core of the page. (1) No published study has administered MOTS-c to a human being; FDA searched and found none, and our own screen of 248 PubMed records agrees  [35,32]. (2) There is no pharmacokinetic profile in any species: no half-life, no bioavailability, no dose-exposure relationship, and FDA states it remains to be determined whether dosing humans can produce active concentrations at all  [35]. (3) The animal literature, strong as it is, never established a dose-response relationship in vivo, and the molecular target through which MOTS-c acts remains unknown, so which organs would be affected in a person cannot be predicted  [35]. (4) No acute, repeat-dose, genotoxicity, reproductive or carcinogenicity study of MOTS-c has been identified  [35]. (5) The human evidence that does exist is measurement and genetics, not intervention: circulating levels move in opposite directions in diabetes and obesity across a 602-participant meta-analysis, and the K14Q association studies compare inherited genotypes rather than testing an injection  [27,17]. (6) The completed human program in this space tested CB4211, an analog, and posted no results and published no paper  [40,32]. (7) FDA reports that the quality attributes needed to assess immunogenicity risk, including impurity, aggregate, endotoxin and bioburden data, were absent from the certificates of analysis and public literature it reviewed  [35]. (8) One Phase 2a trial is recruiting with no results and no published dose  [39]. Anyone selling certainty about MOTS-c is selling ahead of every one of these gaps.

## Questions and answers
### Is MOTS-c really an exercise mimetic?
Partly, and the grade splits. In mice, MOTS-c injections improved treadmill performance at every age tested. In humans, the exercise link runs the other direction: exercise raises your own MOTS-c. No published study has given MOTS-c to a person and measured performance.

The label comes from the research literature itself, not just marketing: papers describe MOTS-c as an with. The evidence behind it splits cleanly by species.In mice, a single 5 mg/kg dose improved treadmill performance in young, middle-aged and old animals, and late-life intermittent dosing raised median lifespan from 912 to 970 days. In humans, the same paper reports the opposite arrow: exercise induces your own MOTS-c in muscle and blood. Human studies since then have measured that response, sometimes finding only a trend or a rise in one ethnic subgroup but not another.So: exercise mimetic is a fair description of what the peptide does in mice, and a description of what exercise does to the peptide in humans. Nobody has published what happens when a human is given it.

### Has MOTS-c ever been tested in humans?
Not with published results. FDA searched and found no clinical studies of MOTS-c administration by any route; our own search of 248 PubMed records agrees. One Phase 2a trial (NCT07505745) is recruiting in China with no results posted and no dose stated in its registry record.

FDA states it directly: reports that its own literature search "did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects", and that no clinical studies or human exposure data exist for any route. Our independent PubMed check found 248 records mentioning MOTS-c in title or abstract, none of them a study administering it to people.One registered trial could change that. is a Phase 2a randomized, double-blind, placebo-controlled study of daily subcutaneous MOTS-c for 12 weeks in 120 planned adults with prediabetes and overweight or obesity, recruiting since February 2026 at a single site in Shenzhen, China. Its primary endpoints are insulin sensitivity and treatment-emergent adverse events. It has posted no results, and the record does not state the dose.

### What about the CB4211 trials? Was that not MOTS-c?
No. CB4211 is a MOTS-c analog, a different molecule built from licensed MOTS-c intellectual property. Its Phase 1a/1b trial in 88 people completed in 2021, posted no results, and has zero PubMed publications. Its registry record never mentions MOTS-c.

A peer-reviewed review states the relationship plainly, calling CB4211 "the MOTS-c analog" whose intellectual property "was licensed by CohBar Inc. and used to develop potent analogs of MOTS-c". An analog is designed to act similarly; it is not the same substance.The trial was real:, a three-part Phase 1a/1b randomized, double-blind, placebo-controlled study of ascending subcutaneous doses in healthy subjects and subjects with nonalcoholic fatty liver disease, 88 participants, completed 19 April 2021. It has no results posted, and a PubMed search for CB4211 returns zero records, so that dataset has never been published. The registry record lists its condition as nonalcoholic fatty liver disease and its interventions only as CB4211 dose levels and placebo; the string MOTS-c does not appear in it.FDA classifies even MOTS-c free base and MOTS-c acetate as distinct substances that may have different safety and efficacy profiles. An analog sits further away than that.

### How strong is the mouse data really?
Strong for mice, and worth respecting. Dosed animals gained less weight, cleared glucose better, ran longer at every age, and lived modestly longer when dosing began at 23.5 months (median 970 versus 912 days). None of it establishes a dose-response curve, and none of it is human data.

Taken at face value, this is a good preclinical file. Mice on a high-fat diet given 0.5 mg/kg/day for eight weeks weighed about 20 percent less than controls, and at 5 mg/kg/day needed roughly 30 percent more glucose to stay euglycemic during insulin clamping. Acute dosing improved treadmill performance in young, middle-aged and old mice, and intermittent dosing from 23.5 months raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days.The qualification comes from FDA's reviewers reading the same papers: the nonclinical work "have been limited to in-vivo and in-vitro rodent models and have not evaluated the dose-response relationships for the effects of MOTS-c in vivo", and the molecular target remains unknown, making it hard to predict which organs would be affected. Doses were also mostly intraperitoneal, a route no consumer uses.

### What does the K14Q longevity research actually prove?
That MOTS-c activity tracks human metabolic health, not that injecting it helps. K14Q is an inherited variant with less activity; men carrying it showed more type 2 diabetes across 27,527 Japanese participants. Association genetics cannot test an injection.

The variant m.1382A>C changes the 14th amino acid of MOTS-c from lysine to glutamine, producing a less active peptide. In a meta-analysis of three Japanese cohorts totalling 27,527 people, men with the C allele had a higher prevalence of type 2 diabetes, and in one cohort only among the least physically active men. Related work links the allele to fast-twitch fiber composition and sprint-athlete frequency, and to muscle mass and grip strength in 683 older Korean men.What that design supports is that lifelong MOTS-c activity matters. What it cannot support is a dosing claim: comparing people who inherited different peptide versions says nothing about what an injection does to an adult. The frequently cited Japanese longevity connection comes from a two-page hypothesis article that proposed the idea and said more research is needed.

### Is MOTS-c FDA approved, and what happened at the July 2026 meeting?
Not approved, in any form. In July 2026 FDA proposed that MOTS-c free base and acetate NOT be added to the 503A compounding list, and its evaluation concluded the criteria weigh against listing. Committee advice is non-binding, and rulemaking is pending.

Drugs@FDA returns no record for MOTS-c as an active ingredient. On 23 July 2026, FDA's Pharmacy Compounding Advisory Committee reviewed MOTS-c-related bulk drug substances against the uses obesity and osteoporosis. FDA's briefing document proposed that neither the free base nor the acetate be included on the 503A Bulks List, and its substance evaluation concluded that a balancing of the criteria weighs against listing.Two clarifications matter. Being added to that list would mean a substance may be used in pharmacy compounding, not that it is FDA approved. And as of this page's verification date FDA had not posted a vote tally or minutes for that session, so this site does not state how the committee voted.

### Is MOTS-c safe?
Unknown, which is not the same as safe. FDA reports no human exposure data by any route and no acute, repeat-dose, genotoxicity, reproductive or carcinogenicity studies. Its adverse-event database holds zero MOTS-c reports, but compounders rarely report to it.

FDA's wording is the clearest available: "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. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown". The same document reports no acute toxicity, repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity or carcinogenicity studies were identified.FAERS searches through March 2025 retrieved no adverse event reports, but FDA notes in the same document that compounders under section 503A generally do not report adverse events, so the empty result reflects a missing reporting pathway more than an established safety record.The named risk is immunogenicity: FDA cannot rule out immune reactions driven by peptide-related impurities and aggregates, because the impurity, aggregate, endotoxin and bioburden data needed to assess it were absent from the certificates of analysis and public literature it reviewed.

### What is the half-life of MOTS-c?
Nobody knows. No in vivo pharmacokinetic study exists in humans or animals. One test-tube experiment showed MOTS-c cut into shorter fragments within 15 minutes in human blood, which is a degradation observation, not a half-life.

FDA states it "did not identify in-vivo pharmacokinetic or toxicokinetic studies of MOTS-c" and that no clinical study provided pharmacokinetic data. That covers every species and every route.The single relevant experiment incubated MOTS-c at 5 micrograms per mL in human whole blood at 37 degrees C and, using high resolution mass spectrometry, found the fragments MOTS-c(2-16), (3-16), (4-16) and (5-16) within 15 minutes. It was built to detect doping, not to characterize dosing. FDA's reading is that it remains to be determined whether dosing humans can generate pharmacologically active concentrations over time.

### My blood test showed high or low MOTS-c. What does that mean?
Less than the marketing suggests. Human studies disagree: MOTS-c ran higher in adults with obesity in one study and lower in obese boys in another, and a 602-participant meta-analysis found it down in diabetes but up in obesity. It behaves like a stress signal, not a fuel gauge.

The human measurement literature is real and genuinely mixed. Plasma MOTS-c did not differ between lean and obese adults in one small study, though it tracked insulin resistance within the lean group. It was lower in obese boys, higher in adults with obesity and unchanged six months after bariatric surgery, and a meta-analysis of 602 participants reported it decreased in diabetes while increasing in obesity.In healthy aging men, blood levels fell with age while muscle expression rose about 1.5-fold. Assays also differ between studies. There is no validated reference range and no evidence that changing a MOTS-c number changes an outcome.

### How do I judge the quality of a MOTS-c vial?
Start with what FDA found missing: no impurity limits, no aggregate testing, no endotoxin or bioburden results in the certificates it reviewed. It also warns that different salts and derivatives are sold under the same name, so a label may not identify what is inside.

FDA's chemistry review is the most useful checklist available, because it names what a typical certificate of analysis omits: impurity limits, aggregate testing, microbial bioburden and bacterial endotoxin results were absent from the certificates and public literature it examined, and endotoxin testing is a critical quality attribute for an injectable. It concluded both the free base and the acetate salt are not well-characterized.Naming is the second hazard. MOTS-c is a common name rather than a United States Adopted Name, and FDA reports encountering multiple salts and derivatives, including different active moieties, sold under it. In the nomination it reviewed, the certificate named one substance in the title and another by CAS number.Storage advice online traces to supplier pages rather than stability studies, and no validated shelf life exists for any finished MOTS-c product.

### Will MOTS-c cause a failed drug test?
Yes, it is prohibited. The 2026 WADA Prohibited List names MOTS-c by full name under S4.4.1, AMPK activators, within hormone and metabolic modulators, prohibited at all times. A validated plasma detection method has been published since 2019.

The 2026 Prohibited List names it explicitly: section S4.4.1 lists "Activators of the AMP-activated protein kinase (AMPK), e.g.... mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)", within the S4 hormone and metabolic modulators class, which is prohibited at all times. FDA notes the same status reaching athletes through the Global Drug Reference Online database.Detection is not theoretical: a liquid chromatography mass spectrometry method for MOTS-c in doping-control plasma was developed and validated in 2019.

### What is the correct MOTS-c dose?
There is not one. No human dose-finding study exists, the one registered trial does not publish its dose, and FDA notes the animal literature never established a dose-response relationship. Published animal doses ranged from 0.5 to 15 mg/kg, mostly intraperitoneal.

Every element needed to state a dose is missing. No published human dose-finding study exists; the registered Phase 2a trial lists only "fixed dose once daily for 12 weeks" without a milligram amount; and FDA reports the animal work "have not evaluated the dose-response relationships for the effects of MOTS-c in vivo".What exists are animal doses, which our study-dose explorer lists with species and route attached: 0.5 and 5 mg/kg/day in the discovery mouse work, 5 mg/kg acute and 15 mg/kg three times weekly in the lifespan study, and 15 mg/kg/day in the immobilization model. Converting those to a human dose requires pharmacokinetic data that does not exist for this peptide in any species.

### Does MOTS-c extend lifespan?
In mice, modestly and in one study: dosing from 23.5 months raised median lifespan from 912 to 970 days. In humans, the longevity link is genetic association, not an intervention. No human lifespan or healthspan trial of MOTS-c exists.

The mouse result is specific and worth stating exactly: intermittent MOTS-c begun at 23.5 months of age raised median lifespan from 912 to 970 days and maximal lifespan from 1047 to 1120 days, alongside improved physical capacity. That is one study, in one strain, with one dosing schedule.The human longevity association is a different kind of evidence entirely: it comes from an inherited variant in Northeast Asian populations and from a hypothesis article that explicitly called for more research. Reviewers in the field state that whether these peptides can be harnessed into therapies remains to be fully determined.

## References
1. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/)
2. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. https://pmc.ncbi.nlm.nih.gov/articles/PMC6185997/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC6185997/)
3. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. https://pmc.ncbi.nlm.nih.gov/articles/PMC7817689/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC7817689/)
4. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. https://pmc.ncbi.nlm.nih.gov/articles/PMC11570452/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC11570452/)
5. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. https://europepmc.org/article/MED/27237975
6. MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-beta/Smad pathway. https://europepmc.org/article/MED/30468456
7. MOTS-c inhibits Osteolysis in the Mouse Calvaria by affecting osteocyte-osteoclast crosstalk via regulating mitochondrial function. https://europepmc.org/article/MED/31369811
8. Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation. https://pmc.ncbi.nlm.nih.gov/articles/PMC6567243/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC6567243/)
9. Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway. https://europepmc.org/article/MED/31694019
10. MOTS-c reduces myostatin and muscle atrophy signaling. https://pmc.ncbi.nlm.nih.gov/articles/PMC8238132/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC8238132/)
11. Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration. https://pmc.ncbi.nlm.nih.gov/articles/PMC11196098/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC11196098/)
12. MOTS-c partially protects against skeletal muscle deterioration in C26 cachexia. https://pmc.ncbi.nlm.nih.gov/articles/PMC13243040/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC13243040/)
13. Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model. https://pmc.ncbi.nlm.nih.gov/articles/PMC13394035/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC13394035/)
14. MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway. https://europepmc.org/article/MED/40472776
15. Development of a mass spectrometry based detection method for the mitochondrion-derived peptide MOTS-c in plasma samples for doping control purposes. https://europepmc.org/article/MED/30394592
16. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? https://pmc.ncbi.nlm.nih.gov/articles/PMC4693465/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC4693465/)
17. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC7880332/)
18. The MOTS-c K14Q polymorphism in the mtDNA is associated with muscle fiber composition and muscular performance. https://pmc.ncbi.nlm.nih.gov/articles/PMC8741734/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC8741734/)
19. The Relationship Between MOTS-c K14Q Polymorphism and Sarcopenia, Blood Lipids, and Mental Health in Older Korean Adults. https://pmc.ncbi.nlm.nih.gov/articles/PMC11504729/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC11504729/)
20. Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals. https://europepmc.org/article/MED/29593067
21. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. https://europepmc.org/article/MED/29691953
22. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. https://pmc.ncbi.nlm.nih.gov/articles/PMC7138593/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC7138593/)
23. Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes. https://europepmc.org/article/MED/34419510
24. beta-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease. https://europepmc.org/article/MED/32052315
25. MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake-A Preliminary Study. https://pmc.ncbi.nlm.nih.gov/articles/PMC10573682/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC10573682/)
26. Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss. https://pmc.ncbi.nlm.nih.gov/articles/PMC12807633/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC12807633/)
27. The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis. https://pmc.ncbi.nlm.nih.gov/articles/PMC11331736/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC11331736/)
28. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. https://pmc.ncbi.nlm.nih.gov/articles/PMC12854548/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC12854548/)
29. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. https://pmc.ncbi.nlm.nih.gov/articles/PMC8376922/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC8376922/)
30. Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization. https://europepmc.org/article/MED/40674654
31. Circulating levels of MOTS-c in patients with breast cancer treated with metformin. https://pmc.ncbi.nlm.nih.gov/articles/PMC10008497/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC10008497/)
32. Mitochondria-derived peptides in aging and healthspan. https://pmc.ncbi.nlm.nih.gov/articles/PMC9057581/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC9057581/)
33. Mitochondrial-derived peptides in energy metabolism. https://pmc.ncbi.nlm.nih.gov/articles/PMC7750512/ (record: https://pmc.ncbi.nlm.nih.gov/articles/PMC7750512/)
34. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
35. FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026: Evaluation of MOTS-c-related Bulk Drug Substances (MOTS-c (free base) and MOTS-c acetate) for Inclusion on the 503A Bulk Drug Substances List https://www.fda.gov/media/193347/download
36. FDA Briefing Document, Pharmacy Compounding Advisory Committee (PCAC) Meeting, July 23-24, 2026 https://www.fda.gov/media/193342/download
37. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee Meeting Announcement https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026
38. Drugs@FDA API query for active ingredient mots-c https://api.fda.gov/drug/drugsfda.json?search=products.active_ingredients.name:%22mots-c%22&limit=3
39. A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity https://clinicaltrials.gov/study/NCT07505745
40. A Phase 1a/1b Study of Safety, Tolerability, and Pharmacokinetics of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease https://clinicaltrials.gov/study/NCT03998514
41. PubChem CID 146675088 (MOTS-c) property and synonym records https://pubchem.ncbi.nlm.nih.gov/compound/146675088
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