Metabolic In Vitro Research Only

MOTS-c: Mitochondrial Peptide, AMPK Activation & Exercise Mimetic Research

mtDNA Encoded in Mitochondrial DNA — Not Nuclear DNA

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid mitochondria-derived peptide (MDP) discovered in 2015 by Changhan Lee at USC — encoded not in nuclear DNA but mitochondrial DNA. In the landmark Cell Metabolism discovery paper, exogenous MOTS-c completely reversed high-fat diet-induced insulin resistance and obesity in mice. A genomic analysis of centenarians identified MOTS-c variants significantly enriched in long-lived Japanese men — the first human genetic evidence linking mitochondrial peptides to exceptional longevity.

For in vitro laboratory research use only. Not for human consumption. All findings described are from preclinical or in vitro models.

MECHANISMS OF ACTION

In vitro and preclinical mechanistic observations

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AMPK Master Metabolic Activation

Robustly activates AMP-activated protein kinase (AMPK) — the master metabolic sensor that mimics cellular effects of exercise and caloric restriction simultaneously.

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Folate Pathway MTHFD2 Inhibition

Inhibits MTHFD2 in the folate cycle, leading to AICAR accumulation — a potent AMPK activator operating through a mechanism similar to metformin but via mitochondrial origin.

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Exercise Mimetic Signalling

MOTS-c levels rise in skeletal muscle during exercise. Exogenous MOTS-c replicates metabolic benefits of exercise including glucose uptake, fat oxidation, and mitochondrial biogenesis.

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Longevity Gene Activation

Activates Nrf2, FOXO, and other longevity-associated transcription factors, and restores metabolic flexibility in aged animals — even when administered late in life.

KEY RESEARCH DATA

Quantitative findings from published preclinical research

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mtDNA

Encoded In

Mitochondrial DNA — 2015 discovery

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Cell Met

Discovery Journal

Lee et al. 2015 — landmark paper

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100+

Centenarian Association

Zempo et al. 2021 Commun Biol

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↑AMPK

Primary Mechanism

Master metabolic sensor activation

MOTS-c Metabolic Effects vs. Control — High-Fat Diet Mouse Model

Insulin Sensitivity

Body Weight Reduction

Fat Mass Loss

Physical Performance

Glucose Uptake

Data: Lee et al. (2015) Cell Metabolism; Kim et al. (2018) Cell Metabolism. PMID 25738459 / 29307489.

PRECLINICAL SAFETY PROFILE

Observed tolerability data from in vitro and animal model research

95%

Tolerability

Low Severity

Injection-Site Rxn

Low Severity

Limited Human Data

Medium Severity

Safety data reflects preclinical observations only. Human clinical safety profiles may differ substantially. For in vitro laboratory research use only. Not for human consumption.