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Really Research Review

22

Reference shelf

The trials, reviews and experimental reports discussed across Really Research Review.

Selected starting papers

The GHK-containing hair trial starts the review’s central question about comparison groups and shared credit. Its formulation contains both GHK and 5-aminolevulinic acid.

For NAD+, the 2025 human evidence review supplies the broad clinical assessment, while the NMN muscle trial supplies a selective physiological result.

The MOTS-c dialysis study is observational. Its human participants did not receive MOTS-c. The mouse performance study addresses an intervention in a different species.

For semaglutide, STEP 1, SELECT and FLOW examine weight, cardiovascular and kidney outcomes, respectively. SURMOUNT-5 supplies the direct weight comparison with tirzepatide.

The complete reading list follows.

  1. 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. ↗
  2. 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. ↗
  3. 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. ↗
  4. Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021. ↗
  5. 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. ↗
  6. Camacho-Pereira J, Tarragó MG, Chini CCS, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016;23:1127-1139. ↗
  7. Koay YC, McIntosh B, Ng YH, et al. The Heart Has Intrinsic Ketogenic Capacity that Mediates NAD(+) Therapy in HFpEF. Circulation Research. 2025;136:1113-1130. ↗
  8. 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. ↗
  9. 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. ↗
  10. 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. ↗
  11. 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. ↗
  12. 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. ↗
  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. Aronne LJ, et al. (SURMOUNT-5 Investigators). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025. ↗
  19. Perkovic V, et al. (FLOW Trial Committees and Investigators). Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024. ↗
  20. Lincoff AM, et al. (SELECT Trial Investigators). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023. ↗
  21. Wilding JPH, et al. (STEP 1 Study Group). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. ↗
  22. Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol (Lausanne). 2021. ↗