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MOTS-c Reviews

A pixel-clean literature digest of the mitochondrial-derived peptide MOTS-c — what the aging and longevity research actually measured, and where the regulatory and access lines really fall.

REFERENCES // EACH CLAIM

MOTS-c peptide references for each claim

When Lee's team first studied MOTS-c, it wanted to learn how cells use fuel. That paper began a list that now lets you check each later claim.

Back to the researchWhat aging studies found

How the numbered notes help you check a claim

Notes [1]-[15] point to the studies used here. Each study title links to PubMed, a public medical library where you can read a short account of the work.

Notes [F1]-[F3] point to FDA pages used for MOTS-c legal status. When you see a note after a claim, you can match its number here.

I'd check the exact paper before making much of a claim. These MOTS-c references don't add anything beyond what the named sources say.

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. ↗
  2. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. ↗
  3. Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28(3):516-524.e7. ↗
  4. Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023;21(1):36. (Reference frame for MOTS-c biology, research routes/doses, and the absence of completed human interventional trials.) ↗
  5. Kumagai H, Kim SJ, Miller B, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience. 2024;27(11):111212. ↗
  6. Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 2022;23(19):11991. ↗
  7. Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023;13(1):125. (Synthesis of MOTS-c metabolic actions, study designs, and durations.) ↗
  8. Zempo H, Kim SJ, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1801-1817. ↗
  9. Cobb LJ, Lee C, Xiao J, Yen K, Wong RG, Nakamura HK, Mehta HH, Gao Q, Ashur C, Huffman DM, Wan J, Muzumdar R, Barzilai N, Cohen P. Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY). 2016;8(4):796-809. ↗
  10. Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes Metab J. 2023;47(3):315-324. ↗
  11. Luo YH, Xie L, Li JY, Xie Y, Li MQ, Zhou L. Serum MOTS-C Levels are Decreased in Obese Children and Associated with Vascular Endothelial Function. Diabetes Metab Syndr Obes. 2023;16:1125-1133. ↗
  12. Bolignano D, Greco M, Presta P, Duni A, et al. The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study. Blood Purif. 2024;53(9):739-749. ↗
  13. Domin R, Pytka M, Ruchala M. MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake - A Preliminary Study. Int J Mol Sci. 2023;24(19):14951. ↗
  14. Fuku N, Pareja-Galeano H, Zempo H, et al. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell. 2015;14(6):921-923. ↗
  15. D'Souza RF, Woodhead JST, Hedges CP, et al. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. Aging (Albany NY). 2020;12(5):5044-5065. ↗
  16. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA.gov. (Defines the 503A bulks-list framework, the USP/NF-monograph / component-of-approved-drug / bulks-list eligibility test, and the PCAC nomination process.) ↗
  17. U.S. Food and Drug Administration. Human Drug Compounding (Section 503A / 503B framework and access pathway). FDA.gov. (Basis for the lawful access pathway: licensed-prescriber evaluation, valid patient-specific prescription, 503A compounding pharmacy or 503B outsourcing facility, with telehealth as a front-end consultation channel and the ingredient-eligibility caveat.) ↗
  18. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. FDA.gov. (Public calendar listing BPC-157, KPV, TB-500, and MOTs-C as bulk drug substances 'being considered for inclusion on the 503A Bulks List' to be discussed at this scheduled meeting; a scheduled discussion of substances under evaluation, not a decision or outcome.) ↗