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LongevityAnimal / preclinical only

MOTS-c

Mitochondrial-derived peptide encoded in the 12S rRNA. Preclinical data on insulin sensitivity, exercise capacity, and metabolic health. No FDA approval. Human data limited to small studies.

Educational only — not medical advice. SmartPeptide does not prescribe, diagnose, or treat. Always consult a licensed healthcare provider before using any peptide, supplement, medication, or protocol.

What the research shows

Rodent and in-vitro work suggests MOTS-c improves insulin sensitivity and modulates metabolic pathways via AMPK. Lee et al. (Cell Metab 2015) is the foundational paper.

What's still experimental

Virtually all human use is experimental. Dose-finding, route of administration, and durability of effect are unestablished.

Anecdotal / community reports

Heavy community interest for 'longevity stacks'. Self-reported energy/recovery improvements are common but uncontrolled.

Anecdotal reports are NOT scientific evidence. They reflect personal experience and may not generalize.

FDA approval status

Source: openFDA + DailyMed (NIH/NLM)
No FDA-approved drug label exists for “MOTS-c”. This peptide is not currently approved by the FDA as a finished pharmaceutical product. Any commercial product claiming FDA approval should be treated with suspicion.

Doses studied in research

Source: Published clinical trial

What published trials tested or FDA-approved labels specify. Reporting research facts — not a SmartPeptide recommendation.

Community-anecdotal range — NOT a SmartPeptide recommendation

The doses below are aggregated from research-peptide community forums (Reddit, biohacker discussions). They are NOT supported by clinical trials, NOT FDA-approved, and NOT a SmartPeptide recommendation. Source purity, dose accuracy, and user-reported outcomes are unverifiable. We display this only because the information is publicly available elsewhere — visitors should absolutely consult a licensed clinician familiar with experimental peptides before any use.

Community-anecdotal — not evidence-basedBiohacker / longevity community forums (uncited aggregate)
Indication studied: Community-discussed for mitochondrial/insulin sensitivity (no human RCT)
Typical
5mg(5,000 µg)
1-2x weekly · subcutaneous

Most-discussed range

Open calculator
Maximum
10mg(10,000 µg)
1-2x weekly · subcutaneous

Upper end of community discussion

Open calculator

Notes from the source: Only preclinical (rodent) data exists. The FDA has issued enforcement actions against companies marketing MOTS-c as injectable for human use.

Important framing: The numbers above are what published trials tested or what FDA-approved labels specify. They are NOT a SmartPeptide recommendation for you. Trial doses come paired with screening, monitoring, and clinician oversight. Always consult a licensed clinician before any peptide use.

How clinicians typically protocol this

Third-party reference · not our recommendation

Dosing phases, cycle lengths, and administration timing as listed in a compounding-pharmacy clinician reference guide. Shown so you can see what a real protocol looks like — and bring informed questions to a licensed clinician.

Third-party protocol referenceCompounding-pharmacy clinician protocol reference (Nov 2025)

Dose numbers, frequencies, and cycle lengths in this panel are extracted from a clinician-facing reference protocol distributed by a US-based compounding pharmacy in November 2025. SmartPeptide has paraphrased all descriptive text and adds no endorsement. Always consult a licensed clinician.

Energy Support

16-amino-acid mitochondrial-encoded peptide; studied for metabolic and mitochondrial signaling.

Protocol phases

Typical
5–10 mg2–3× weekly
subcutaneous
Cycle length

4 weeks on, then a break.

Protocol notes: Reference flags reduced stability post-reconstitution (some literature suggests as little as ~10 minutes at room temp — data still emerging).

Reconstitution calculator Storage & reconstitution guide
Not medical advice. SmartPeptide does not prescribe, diagnose, or treat. The protocol above reproduces dose figures from a third-party clinician reference so you can see what compounding-pharmacy guidance typically looks like — it is not a recommendation for you, and it has not been validated against peer-reviewed dose-ranging trials. Many of these compounds are not FDA-approved for human use. Work with a licensed clinician familiar with peptide therapy before considering anything here.

FDA enforcement & recalls

Live · openFDA Drug Enforcement API
No FDA enforcement actions (recalls, market withdrawals, safety alerts) on record for “MOTS-c”. This is the expected baseline for most peptides — the absence of recalls does NOT imply general safety, only that no formal FDA enforcement has been initiated against approved formulations.

Mechanism & targets

ChEMBL · UniProt · Open Targets

Molecule (ChEMBL)

View on ChEMBL
Formula
C54H46Cl4N6O12

Protein targets (UniProt)

  • Mitochondrial-derived peptide MOTS-c
    A0A0C5B5G6gene: MT-RNR1Homo sapiens· 16 aaReviewed

    Regulates insulin sensitivity and metabolic homeostasis (PubMed:25738459, PubMed:33468709). Inhibits the folate cycle, thereby reducing de novo purine biosynthesis which leads to the accumulation of the de novo purine synthesis intermediate 5-aminoimidazole-4-carboxamide (AICAR) and the activation of the metabolic regulator 5'-AMP-activated protein kinase (AMPK) (PubMed:25738459). Protects against age-dependent and diet-induced insulin resistance as well as diet-induced obesity (PubMed:25738459)…

  • Cyclic AMP-dependent transcription factor ATF-1
    P18846gene: ATF1Homo sapiens· 271 aaReviewed

    This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation

  • Nuclear factor erythroid 2-related factor 2
    Q16236gene: NFE2L2Homo sapiens· 605 aaReviewed

    Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:11035812, PubMed:19489739, PubMed:29018201, PubMed:31398338). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:11035812, PubMed:15601839, PubMe…

Live research

PubMed · ClinicalTrials.gov · Europe PMC · OpenAlex
PubMed papers
254
total
Human studies
143
MeSH: humans
Clinical trials
5
published
Active trials
5
9 total registered

Recent PubMed studies

Search "MOTS-c" on PubMed

Europe PMC — 10,165 additional records

Includes EU/UK studies and PubMed Central full-text articles. Often surfaces research weeks before PubMed indexes it.

Research volume (OpenAlex topic graph)

Total works
575,176
all years
Last 5 years
159,507
recent activity
Open access
565,404
freely readable
OA share
98%
of all works

Human clinical evidence

Semantic Scholar · AI TLDRs · influence-ranked
Semantic Scholar API is currently rate-limited.

Human-study summaries for “MOTS-c” are available on Semantic Scholar but the shared free-tier API quota is exhausted right now. Try refreshing in a few minutes, or check the PubMed and Europe PMC panels above for the same literature.

Research funding & verification

NIH RePORTER · CrossRef DOI registry

NIH-funded research

U.S. National Institutes of Health
Funded projects
408,839
all years
Top award sum
$1562.9M
aggregate USD
Years covered
24
research span
Largest active / recent grants

Publication landscape

CrossRef · DOI registry
Indexed works (CrossRef)
12,518
all DOIs registered
Retracted papers
0
no retractions on record
Top funders of indexed research
  • National Natural Science Foundation of China41 works
  • Horizon 202011 works
  • Ministère des Affaires Etrangères10 works
  • Centre National de la Recherche Scientifique10 works
  • American Federation for Aging Research7 works
  • National Institutes of Health6 works

Funder diversity is a credibility signal. Research concentrated in a single drug company's funding warrants more scrutiny than research funded across NIH, charities, and academic grants.

Preprints — cutting edge

bioRxiv · medRxiv · via Europe PMC

Preprints have NOT been peer-reviewed. They are early research shared by authors before formal validation. Treat findings as preliminary.

Showing 6 of 38 preprints indexed by Europe PMC.

Known risks

Unknown long-term safety in humans. No structured pharmacovigilance.

Reported side effects

Sparse human reports; mostly injection-site irritation noted in anecdotal logs.

FDA adverse event reports (FAERS)

Updated quarterly by FDA
No reports found in the FDA Adverse Event Reporting System for “MOTS-c”. This is normal for research-only peptides that are not marketed as FDA-approved drugs.

What requires medical supervision

Without FDA approval or established human safety data, any use should be informed by a clinician familiar with experimental peptides.

Questions for your clinician

  • What's the strongest human evidence for my goal?
  • How do we evaluate baseline + response objectively?
  • What's our stop criteria?

Editorially curated references

Discussions about MOTS-c

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