MOTS-c Direct

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References: the MOTS-c studies and regulatory sources

Every quantitative claim on this site maps to a numbered entry here. Peer-reviewed literature and primary FDA pages.

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Peer-Reviewed Literature

The studies below are PubMed-indexed and carry DOIs. They underpin the mechanism, metabolic, exercise-mimetic, and human-biomarker findings summarized across this site. Where a claim cites a number — a dose, a P-value, an effect — it resolves to one of these entries. See the underlying MOTS-c research for the narrative.

Regulatory Sources

The regulatory standing on MOTS-c legal status and 503A access is drawn from primary FDA pages: the Section 503A bulk-substances framework, the access pathway for compounded medications, and the FDA advisory-committee calendar listing the July 23-24, 2026 PCAC meeting at which MOTS-c is scheduled for discussion. These describe present-tense status only; no future FDA action is asserted as fact.

  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. ↗
  5. 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. ↗
  6. 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. ↗
  7. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose. Physiol Rep. 2022;10(13):e15377. ↗
  8. Dieli-Conwright CM, Sami N, Norris MK, Wan J, Kumagai H, Kim SJ, Cohen P. Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. Sci Rep. 2021;11(1):16916. ↗
  9. Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. ↗
  10. Tekin S, Bir LS, Avci E, et al. Comparison of Serum Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) Levels in Patients With Multiple Sclerosis and Healthy Controls. Cureus. 2022;14(7):e26981. ↗
  11. 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. ↗
  12. Kim SJ, Miller B, Kumagai H, Silverstein AR, Flores M, Yen K. Mitochondrial-derived peptides in aging and age-related diseases. GeroScience. 2020;43(3):1113-1121. ↗
  13. 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(11-12):916-926. ↗
  14. Parseh S, Shakerian S, Tabandeh MR, Habibi A. An 8-week study on the effects of high and moderate-intensity interval exercises on mitochondrial MOTS-C changes and their relation to metabolic markers in male diabetic sand rats. Diabetes Res Clin Pract. 2024;211:111656. ↗
  15. 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. ↗
  16. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA, Human Drug Compounding. ↗
  17. U.S. Food and Drug Administration. Compounding and the FDA: Questions and Answers (503A patient-specific compounding and 503B outsourcing facilities). FDA, Human Drug Compounding. ↗
  18. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (agenda listing BPC-157, KPV, TB-500, and MOTS-c as bulk drug substances being considered for inclusion on the 503A Bulks List). FDA, Advisory Committee Calendar. ↗