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Longevity Peptide

Reading list

The withdrawal paper is a good place to start. The other studies ask questions on quite different timescales.

Start with withdrawal

For the argument at the centre of this site, start with the tesamorelin program that followed continued treatment and withdrawal. Its fat-reaccumulation finding gives the maintenance question a concrete human result.

For shorter windows, the NR safety and metabolism trial reports blood changes through 8 weeks, and the NMN muscle-insulin trial follows prediabetic, postmenopausal women for 10 weeks. The 2025 NAD+ precursor review considers the wider human evidence.

For MOTS-c, the mouse physical-capacity paper and the dialysis cohort measuring circulating MOTS-c are useful companions precisely because they did different things. The first tested treatment in animals; the second followed naturally occurring blood levels in people.

The SELECT cardiovascular paper and FLOW kidney paper count clinical events in distinct at-risk populations. The semaglutide safety review is a starting point for the adverse-effect discussion. Full bibliographic details follow.

  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. Badran AS, et al. Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials. Obesity Research & Clinical Practice. 2026;20(1):2-12. ↗
  14. National Institute of Diabetes and Digestive and Kidney Diseases (LiverTox). Tesamorelin - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. NCBI Bookshelf (NIH). 2018. ↗
  15. Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380-389. ↗
  16. Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. Journal of Clinical Endocrinology and Metabolism. 2011;96(1):150-158. ↗
  17. Falutz J, Allas S, Mamputu JC, Potvin D, Kotler D, Somero M, Berger D, Brown S, Richmond G, Fessel J, Turner R, Grinspoon S. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-1728. ↗
  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. ↗