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A bulletin on peptides, aging and elapsed time

Reading list

Research bibliography

The full list includes acute hormone testing, animal experiments, skin research, human precursor trials and observational follow-up.

Reading across the studies

For the opening contrast in time, read the ipamorelin pharmacokinetic study alongside the bowel-resection trial. One characterized the drug and a hormone response; the other tested a recovery outcome.

For NAD+, the 2025 clinical review considers the human precursor results together. The topical GHK review gives particular attention to passage through skin. The MOTS-c dialysis cohort is a longer human follow-up of existing blood levels, with no experimental MOTS-c treatment.

The different clocks persuade me to resist treating these studies as interchangeable. The complete citations follow.

  1. 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. ↗
  2. 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 Purification. 2024;53(10):824-837. ↗
  3. 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. Journal of Translational Medicine. 2023;21(1):36. ↗
  4. 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. Nature Communications. 2021;12(1):470. ↗
  5. 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 Metabolism. 2018;28(3):516-524.e7. ↗
  6. 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 Metabolism. 2015;21(3):443-454. ↗
  7. Pham T, Taberner A, Hickey A, Han JC. Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart. Frontiers in Physiology. 2025;16:1602271. ↗
  8. Vinten KT, Trętowicz MM, Coskun E, van Weeghel M, Cantó C, Zapata-Pérez R, Janssens GE, Houtkooper RH. NAD(+) precursor supplementation in human ageing: clinical evidence and challenges. Nat Metab. 2025;7:1974-1990. ↗
  9. Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience 2023. 2023;45:29-43. ↗
  10. Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372:1224-1229. ↗
  11. Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. ↗
  12. Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019;9:9772. ↗
  13. Mortazavi SM, Mohammadi Vadoud SA, Moghimi HR. Topically applied GHK as an anti-wrinkle peptide: Advantages, problems and prospective. BioImpacts. 2025;15:30071. ↗
  14. Pickart L, Margolina A. Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International Journal of Molecular Sciences. 2018;19(7):1987. ↗
  15. Lee WJ, Sim HB, Jang YH, Lee SJ, Kim DW, Yim SH. Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide on Hair Growth. Annals of Dermatology. 2016;28(4):438-443. ↗
  16. Pickart L, Vasquez-Soltero JM, Margolina A. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. BioMed Research International. 2015;2015:648108. ↗
  17. Hostynek JJ, Dreher F, Maibach HI. Human skin penetration of a copper tripeptide in vitro as a function of skin layer. Inflammation Research. 2011;60(1):79-86. ↗
  18. Lu Z, Ngan MP, Liu JYH, Yang L, Tu L, Chan SW, Giuliano C, Lovati E, Pietra C, Rudd JA. The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism. Physiology & Behavior. 2024;284:114644. ↗
  19. Stokes AH, Falls JG, Yoon L, Cariello N, Faiola B, Colton HM, Jordan HL, Berridge BR. Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. International Journal of Toxicology. 2015;34(2):151-161. ↗
  20. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. International Journal of Colorectal Disease. 2014;29(12):1527-1534. ↗
  21. Gobburu JV, Agerso H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical Research. 1999;16(9):1412-1416. ↗
  22. Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Hormone & IGF Research. 1999;9(2):106-113. ↗