# MOTS-c peptide references: the cited studies and regulatory sources

> The MOTS-c peptide references: PubMed-indexed studies behind the mechanism, metabolic, and exercise findings, plus the FDA regulatory sources, with DOIs and PMIDs.

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

## 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](/research) for the narrative.

## Regulatory Sources

The regulatory standing on [MOTS-c legal status and 503A access](/legal-status) 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.

## References

[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. https://pubmed.ncbi.nlm.nih.gov/25738459/
[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. https://pubmed.ncbi.nlm.nih.gov/33473109/
[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. https://pubmed.ncbi.nlm.nih.gov/29983246/
[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. https://pubmed.ncbi.nlm.nih.gov/36670507/
[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. https://pubmed.ncbi.nlm.nih.gov/32182209/
[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. https://pubmed.ncbi.nlm.nih.gov/37834399/
[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. https://pubmed.ncbi.nlm.nih.gov/35808870/
[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. https://pubmed.ncbi.nlm.nih.gov/34413391/
[9] Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. https://pubmed.ncbi.nlm.nih.gov/36936170/
[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. https://pubmed.ncbi.nlm.nih.gov/35989823/
[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. https://pubmed.ncbi.nlm.nih.gov/39559755/
[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. https://pubmed.ncbi.nlm.nih.gov/32910336/
[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. https://pubmed.ncbi.nlm.nih.gov/39111290/
[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. https://pubmed.ncbi.nlm.nih.gov/38636847/
[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. https://pubmed.ncbi.nlm.nih.gov/26289118/
[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. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act
[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. https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers
[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. https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026

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A cobalt-glazed azulejo panel of the MOTS-c record — the mitochondrial peptide's metabolic and exercise-mimetic findings set tile by tile and cited to source, the empty human-trial squares left openly unglazed, and the FDA 503A standing painted before anything else; no clinic behind the panel and nothing here dispensed or sold.