--- title: "MOTS-c | PepTracker Pro" url: https://peptrackerpro.com/peptides/mots-c description: "A mitochondrial-derived peptide studied for metabolic regulation, exercise mimetic effects, and longevity." lang: en --- Skip to main content **Educational information only.** This site does not provide medical advice. Read full disclaimer (https://peptrackerpro.com/disclaimer) **Research-only content.** This page is for educational purposes and does not constitute medical advice. Read full disclaimer → (https://peptrackerpro.com/research-disclaimer) # MOTS-c Low Evidence A mitochondrial-derived peptide studied for metabolic regulation, exercise mimetic effects, and longevity. Aliases Mitochondrial ORF of the 12S rRNA Type-c Evidence Low Evidence Last Updated 2026-06-21 Reading Time 3 min ## What It Is MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome. It is one of the few known mitochondria-derived peptides (MDPs) with systemic signaling activity. Research has demonstrated its role in metabolic regulation, exercise mimicry, and insulin sensitivity. Circulating MOTS-c levels decline measurably with age, placing it at the forefront of longevity research in 2026. A 2025 study published in Experimental & Molecular Medicine demonstrated that MOTS-c prevents pancreatic islet cell senescence by modifying senescence-associated transcriptional and metabolic profiles in β-cells, delaying diabetes progression in animal models. A separate 2025 study in Frontiers in Physiology showed MOTS-c restores mitochondrial respiration in type 2 diabetic heart tissue, expanding its therapeutic relevance to cardiovascular metabolic disease. In sedentary animal models, exogenous MOTS-c reproduced training-induced metabolic adaptations, earning it the label 'exercise mimetic peptide.' Updated research confirms skeletal muscle MOTS-c levels increase nearly 12-fold during exercise. Exogenous MOTS-c doubled running capacity in mice and reversed age-related physical decline by activating the AMPK/PGC-1α pathway and directly binding casein kinase 2 (CK2). Notably, circulating MOTS-c levels are significantly higher in centenarian populations compared to age-matched controls, suggesting maintained MOTS-c signaling may serve as both a biomarker and driver of successful metabolic aging. A key challenge for clinical translation is MOTS-c's low bioavailability, poor stability, and short half-life — limitations common to mitochondrial-derived peptides that have slowed clinical development. As of April 2026, no active MOTS-c human trials are registered on ClinicalTrials.gov, though a trial using a MOTS-c analog for fatty liver and obesity (NCT03998514) has been registered. MOTS-c is scheduled for PCAC review on July 23, 2026, alongside BPC-157, KPV, and TB-500, to determine whether it can be legally compounded under section 503A. A 2026 study in ScienceDirect examined MOTS-c's role in type 2 diabetes mellitus complications including cardiovascular disease, establishing MOTS-c as a multi-organ protective factor whose deficiency correlates with cardiometabolic risk. Public comments via docket FDA-2025-N-6895 are accepted until July 22, 2026. Also known as: Mitochondrial ORF of the 12S rRNA Type-c ## Regulatory Status Category 1 — Bulk Compounding (PCAC review July 23, 2026) Moved from Category 2 back to Category 1 per HHS announcement February 27, 2026. FDA PCAC will review MOTS-c (free base and acetate) on July 23, 2026 for potential 503A Bulks List inclusion for obesity and osteoporosis indications. Public comment docket FDA-2025-N-6895 open until July 22, 2026. Effective: February 2026 View FDA Source (https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026) ## Evidence Snapshot Low Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Animal (mouse) | Age-dependent physical decline — MOTS-c administration | Doubled running capacity; reversed age-related decline via AMPK/PGC-1α pathway | Source: https://www.nature.com/articles/s41467-020-20790-0 | | Animal (mouse, 2025) | Pancreatic islet cell senescence — diabetes model | MOTS-c prevented β-cell senescence and delayed diabetes progression by modifying senescence-associated transcriptional and metabolic profiles | Source: https://www.nature.com/articles/s12276-025-01521-1 | | Animal (mouse, 2025) | Type 2 diabetic heart — mitochondrial respiration | MOTS-c restored mitochondrial respiration in diabetic cardiac tissue | Source: https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1602271/full | | Observational (human cohort) | Centenarian populations vs age-matched controls | Significantly higher circulating MOTS-c levels in centenarians, suggesting maintained MOTS-c signaling as biomarker of successful metabolic aging | Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC9905433/ | | Review/Preclinical (2026) | MOTS-c in T2DM — risk factors to cardiac complications | MOTS-c deficiency correlates with cardiometabolic risk; multi-organ protective effects documented across diabetic complications | Source: https://www.sciencedirect.com/science/article/abs/pii/S0024320525006459 | ## Commonly Discussed Benefits Metabolism: https://peptrackerpro.com/benefits/metabolism Fat Loss: https://peptrackerpro.com/benefits/fat-loss Longevity: https://peptrackerpro.com/benefits/longevity Muscle Growth: https://peptrackerpro.com/benefits/muscle-growth Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Energy: https://peptrackerpro.com/benefits/energy Researching MOTS-c? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=mots-c) ## Safety & Cautions - Discovery is recent; most data is preclinical - No completed human clinical trials - Long-term effects unknown - Not FDA-approved for any indication - Unlike small-molecule metabolic compounds such as SLU-PP-332 and 5-Amino-1MQ, MOTS-c IS on the FDA's July 23, 2026 PCAC compounding review list — a favorable vote would not legitimize those other compounds ## Comparisons See how MOTS-c compares to related peptides: MOTS-c vs 5-Amino-1MQ: https://peptrackerpro.com/compare/mots-c-vs-5-amino-1mq MOTS-c vs Epithalon: https://peptrackerpro.com/compare/mots-c-vs-epithalon MOTS-c vs Humanin: https://peptrackerpro.com/compare/mots-c-vs-humanin MOTS-c vs NAD+: https://peptrackerpro.com/compare/mots-c-vs-nad MOTS-c vs SLU-PP-332: https://peptrackerpro.com/compare/mots-c-vs-slu-pp-332 MOTS-c vs SS-31: https://peptrackerpro.com/compare/mots-c-vs-ss-31 ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Lee C. et al. — The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metab. 2015 PubMed (https://pubmed.ncbi.nlm.nih.gov/25738459/) 2. [2] MOTS-c prevents pancreatic islet cell senescence to delay diabetes — Exp Mol Med. 2025 PubMed (https://www.nature.com/articles/s12276-025-01521-1) 3. [3] MOTS-c restores mitochondrial respiration in type 2 diabetic heart — Frontiers Physiol. 2025 PubMed (https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1602271/full) 4. [4] MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline — Nature Commun. 2021 PubMed (https://www.nature.com/articles/s41467-020-20790-0) 5. [5] MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications — Life Sciences 2026 PubMed (https://www.sciencedirect.com/science/article/abs/pii/S0024320525006459) 6. [6] FDA — July 23-24, 2026 Meeting of the Pharmacy Compounding Advisory Committee PubMed (https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026) 7. [7] STAT — An obesity drug deep-dive, and peptides move mainstream (June 11, 2026) PubMed (https://www.statnews.com/2026/06/11/an-obesity-drug-deep-dive-and-peptides-move-mainstream/) ### Keep researching in the app - Log MOTS-c to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack Open PepTracker Pro Free: https://app.peptrackerpro.com/?add=mots-c Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### 5-Amino-1MQ Low Evidence A small molecule NNMT inhibitor studied for metabolic enhancement and fat cell reduction. Fat Loss: https://peptrackerpro.com/benefits/fat-loss Metabolism: https://peptrackerpro.com/benefits/metabolism Energy: https://peptrackerpro.com/benefits/energy View Details: https://peptrackerpro.com/peptides/5-amino-1mq \+ Compare: https://peptrackerpro.com/compare?select=5-amino-1mq Track in App: https://app.peptrackerpro.com/?add=5-amino-1mq ### Epithalon Low Evidence A tetrapeptide studied for its potential to activate telomerase and influence biological aging markers. Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Sleep: https://peptrackerpro.com/benefits/sleep Immune Support: https://peptrackerpro.com/benefits/immune-support View Details: https://peptrackerpro.com/peptides/epithalon \+ Compare: https://peptrackerpro.com/compare?select=epithalon Track in App: https://app.peptrackerpro.com/?add=epithalon ### Humanin Low Evidence An endogenous mitochondrial-derived peptide studied for neuroprotection, cellular stress resistance, and longevity, whose blood levels fall with age and are elevated in centenarians. Longevity (https://peptrackerpro.com/benefits/longevity)Anti-Aging (https://peptrackerpro.com/benefits/anti-aging)Neuroprotection (https://peptrackerpro.com/benefits/neuroprotection)Metabolism (https://peptrackerpro.com/benefits/metabolism)+1 more View Details: https://peptrackerpro.com/peptides/humanin \+ Compare: https://peptrackerpro.com/compare?select=humanin Track in App: https://app.peptrackerpro.com/?add=humanin ### NAD+ Medium Evidence A coenzyme essential for cellular energy production, studied for anti-aging and metabolic support. Energy (https://peptrackerpro.com/benefits/energy)Longevity (https://peptrackerpro.com/benefits/longevity)Anti-Aging (https://peptrackerpro.com/benefits/anti-aging)Metabolism (https://peptrackerpro.com/benefits/metabolism)+1 more View Details: https://peptrackerpro.com/peptides/nad \+ Compare: https://peptrackerpro.com/compare?select=nad Track in App: https://app.peptrackerpro.com/?add=nad ### SLU-PP-332 Low Evidence A synthetic ERRα/β/γ pan-agonist studied as an 'exercise mimetic' for endurance, fat oxidation, and metabolic health. Energy: https://peptrackerpro.com/benefits/energy Fat Loss: https://peptrackerpro.com/benefits/fat-loss Metabolism: https://peptrackerpro.com/benefits/metabolism View Details: https://peptrackerpro.com/peptides/slu-pp-332 \+ Compare: https://peptrackerpro.com/compare?select=slu-pp-332 Track in App: https://app.peptrackerpro.com/?add=slu-pp-332 ### SS-31 High Evidence A mitochondria-targeted peptide FDA-approved as FORZINITY (elamipretide) for Barth syndrome in September 2025 — the first FDA-approved mitochondrial-targeted therapeutic. Longevity: https://peptrackerpro.com/benefits/longevity Anti-Aging: https://peptrackerpro.com/benefits/anti-aging Recovery: https://peptrackerpro.com/benefits/recovery Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection View Details: https://peptrackerpro.com/peptides/ss-31 \+ Compare: https://peptrackerpro.com/compare?select=ss-31 Track in App: https://app.peptrackerpro.com/?add=ss-31 ## Structured data ```json [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "MOTS-c", "description": "A mitochondrial-derived peptide studied for metabolic regulation, exercise mimetic effects, and longevity.", "url": "https://peptrackerpro.com/peptides/mots-c", "lastReviewed": "2026-06-21", "reviewedBy": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "isPartOf": { "@type": "WebSite", "name": "PepTracker Pro", "url": "https://peptrackerpro.com" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Peptides", "item": "https://peptrackerpro.com/peptides" }, { "@type": "ListItem", "position": 3, "name": "MOTS-c", "item": "https://peptrackerpro.com/peptides/mots-c" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "People researching mitochondrial-derived peptides?", "acceptedAnswer": { "@type": "Answer", "text": "MOTS-c is a research peptide studied in preclinical models. 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