The mitochondrial‐derived peptide MOTS ‐c: a player in exceptional longevity?
Open accessAbstract
Mitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c). Although more research is needed, we suggest that the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people.
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Functioning predominantly through activation of AMPK, MOTS-c promotes glucose utilization, enhances fatty acid oxidation, and improves insulin sensitivity.
“Functioning predominantly through the activation of AMPK, MOTS-c promotes glucose utilization, enhances fatty acid oxidation, and improves insulin sensitivity”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [116]
The “Mitochondrial-derived peptide MOTS-c” section (page unavailable) says MOTS-c regulates insulin sensitivity and metabolic homeostasis. It does not describe AMPK activation, increased glucose utilization, or enhanced fatty acid oxidation, so those parts of the claim are unsupported by our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn aged mice, exogenous administration of MOTS-c improved physical performance and metabolic profiles, partly through increasing NAD+ availability and modulating sirtuin pathways including SIRT1 and SIRT3.
“In aged mice, the exogenous administration of MOTS-c improved physical performance and metabolic profiles, partly through its ability to increase NAD+ availability and modulate sirtuin pathways, including SIRT1 and SIRT3”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [116]
The “Mitochondrial-derived peptide MOTS-c” section says MOTS-c regulates insulin sensitivity and metabolic homeostasis. It does not report administration to aged mice, improved physical performance, increased NAD+ availability, or effects on SIRT1 or SIRT3; the Conclusions instead call for further mechanistic research. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTreatment with MOTS-C in mice prevents age-dependent and high-fat diet-induced insulin resistance and obesity.
“Interestingly, treatment with MOTS-C in mice prevent agedependent and high-fat diet induced insulin resistance and obesity indicating an important role of mitochondria in the control of fat metabolism probably producing prolongevity effects (Fuku et al., 2015; Lee et al., 2015).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Fuku et al., 2015
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- Authors
- Fuku, N., Pareja‐Galeano, H., Zempo, H., Alis, R., Arai, Y., Lucia, A., & Hirose, N.
- Affiliations
- Juntendo University (JP)
- European University of Madrid Madrid Spain
- Valencia Catholic University Saint Vincent Martyr (ES)
- Keio University (JP)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2015-08-20
- Volume
- 14
- Issue
- 6
- Pages
- 921-923
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1694109520
- Cited by
- 98
- References
- 22
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 5 · 2023: 14 · 2022: 7 · 2021: 7 · 2020: 14 · 2019: 16 · 2018: 10 · 2017: 4 · 2016: 8
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ABACUS. Repositorio de Producción Científica (Universidad Europea) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Grant-in-Aid for Scientific Research (B) (15H03081)
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Fondo de Investigaciones Sanitarias (PI12/00914)
- Fondos FEDER
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- MOTS-c, mitochondrial peptides, mitochondrial DNA, small open reading frames, humanin, exceptional longevity, Japanese population
- MeSH terms
- Aging, DNA, Mitochondrial, Humans, Japan, Longevity, Mitochondria, Peptides, RNA, Ribosomal, Open Reading Frames, Polymorphism, Single Nucleotide, Asian People
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