Covid-19 Research

Research Article

OCLC Number/Unique Identifier: 9528704708

NMN Nicotinamide Mononucleotide Activates Intracellular Energy and Approaches the Prevention and Improvement of Aging

Medicine Group    Start Submission

Satoshi Kawakami*, Yoshitaka Fukuzawa, Hiroyuki Ichikawa, Tsutomu Sato, Takaharu Ide, Yusuke Maeda and Takahiko Yamamoto

Volume3-Issue5
Dates: Received: 2022-05-17 | Accepted: 2022-05-20 | Published: 2022-05-21
Pages: 560-565

Abstract

Aging was defined as one of the diseases by ICD-11. Preventing aging may avoid the risk of various diseases. However, it is difficult to simply prevent aging in daily life. The presence of nutrients is essential there. This time, we reviewed NMN "nicotinamide nucleotide", which is attracting attention as an anti-aging component, and conducted additional experiments using AMPK "AMP-activated protein kinase" and NAD + as indicators to determine whether or not it actually prevents aging gone. As a result, a significant increase in AMPK and NAD + was confirmed, suggesting that NMN may help prevent aging in the future.

FullText HTML FullText PDF DOI: 10.37871/jbres1480


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Copyright

© 2022 Kawakami S, et al. Distributed under Creative Commons CC-BY 4.0

How to cite this article

Kawakami S, Fukuzawa Y, Ichikawa H, Sato T, Ide T, Maeda Y, Yamamoto T. NMN “Nicotinamide Mononucleotide” Activates Intracellular Energy and Approaches the Prevention and Improvement of Aging. J Biomed Res Environ Sci. 2022 May 21; 3(5): 560-565. doi: 10.37871/jbres1480, Article ID: JBRES1480, Available at: https://www.jelsciences.com/articles/jbres1480.pdf


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References


  1. Calimport SRG, Bentley BL. Aging Classified as a Cause of Disease in ICD-11. Rejuvenation Res. 2019 Aug;22(4):281. doi: 10.1089/rej.2019.2242. PMID: 31319768.
  2. Goldsmith TC. On the programmed/non-programmed aging controversy. Biochemistry (Mosc). 2012 Jul;77(7):729-32. doi: 10.1134/S000629791207005X. PMID: 22817536.
  3. Flatt T. A new definition of aging? Front Genet. 2012 Aug 23;3:148. doi: 10.3389/fgene.2012.00148. PMID: 22936945; PMCID: PMC3425790.
  4. Childs BG, Durik M, Baker DJ, van Deursen JM. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med. 2015 Dec;21(12):1424-35. doi: 10.1038/nm.4000. PMID: 26646499; PMCID: PMC4748967.
  5. Gonzalez PS, O'Prey J, Cardaci S, Barthet VJA, Sakamaki JI, Beaumatin F, Roseweir A, Gay DM, Mackay G, Malviya G, Kania E, Ritchie S, Baudot AD, Zunino B, Mrowinska A, Nixon C, Ennis D, Hoyle A, Millan D, McNeish IA, Sansom OJ, Edwards J, Ryan KM. Mannose impairs tumour growth and enhances chemotherapy. Nature. 2018 Nov;563(7733):719-723. doi: 10.1038/s41586-018-0729-3. Epub 2018 Nov 21. PMID: 30464341.
  6. Hardeland R. Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms. J Pineal Res. 2013 Nov;55(4):325-56. doi: 10.1111/jpi.12090. Epub 2013 Sep 23. PMID: 24112071.
  7. Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Morán M, Emanuele E, Joyner MJ, Lucia A. Exercise attenuates the major hallmarks of aging. Rejuvenation Res. 2015 Feb;18(1):57-89. doi: 10.1089/rej.2014.1623. PMID: 25431878; PMCID: PMC4340807.
  8. Liochev SI. Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med. 2013 Jul;60:1-4. doi: 10.1016/j.freeradbiomed.2013.02.011. Epub 2013 Feb 19. PMID: 23434764.
  9. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018 Apr 26;13:757-772. doi: 10.2147/CIA.S158513. PMID: 29731617; PMCID: PMC5927356.
  10. Cochemé HM, Quin C, McQuaker SJ, Cabreiro F, Logan A, Prime TA, Abakumova I, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RA, Saeed S, Carré JE, Singer M, Gems D, Hartley RC, Partridge L, Murphy MP. Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab. 2011 Mar 2;13(3):340-50. doi: 10.1016/j.cmet.2011.02.003. PMID: 21356523; PMCID: PMC4413513.
  11. Powers SK, Ji LL, Kavazis AN, Jackson MJ. Reactive oxygen species: impact on skeletal muscle. Compr Physiol. 2011 Apr;1(2):941-69. doi: 10.1002/cphy.c100054. PMID: 23737208; PMCID: PMC3893116.
  12. Rosa AC, Corsi D, Cavi N, Bruni N, Dosio F. Superoxide Dismutase Administration: A Review of Proposed Human Uses. Molecules. 2021 Mar 25;26(7):1844. doi: 10.3390/molecules26071844. PMID: 33805942; PMCID: PMC8037464.
  13. Nandi A, Yan LJ, Jana CK, Das N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid Med Cell Longev. 2019 Nov 11;2019:9613090. doi: 10.1155/2019/9613090. PMID: 31827713; PMCID: PMC6885225.
  14. Doseděl M, Jirkovský E, Macáková K, Krčmová LK, Javorská L, Pourová J, Mercolini L, Remião F, Nováková L, Mladěnka P, On Behalf Of The Oemonom. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients. 2021 Feb 13;13(2):615. doi: 10.3390/nu13020615. PMID: 33668681; PMCID: PMC7918462.
  15. Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr. 2007;27:347-62. doi: 10.1146/annurev.nutr.27.061406.093819. PMID: 17439363.
  16. Kumar S, Pandey AK. Free radicals: health implications and their mitigation by herbals. Br J Med Med Res. 2015;7:438-457. doi: 10.9734/BJMMR/2015/16284.
  17. Burkewitz K, Zhang Y, Mair WB. AMPK at the nexus of energetics and aging. Cell Metab. 2014 Jul 1;20(1):10-25. doi: 10.1016/j.cmet.2014.03.002. Epub 2014 Apr 10. PMID: 24726383; PMCID: PMC4287273.
  18. Yuichi Yokoyama. Regulation of glucose and lipid metabolism via AMPK, the annual proceedings of Gifu Pharmaceutical University. 2013;62:68-74.
  19. Park DW, Jiang S, Tadie JM, Stigler WS, Gao Y, Deshane J, Abraham E, Zmijewski JW. Activation of AMPK enhances neutrophil chemotaxis and bacterial killing. Mol Med. 2013 Nov 8;19(1):387-98. doi: 10.2119/molmed.2013.00065. PMID: 24091934; PMCID: PMC3883969.
  20. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018 Feb;19(2):121-135. doi: 10.1038/nrm.2017.95. Epub 2017 Oct 4. PMID: 28974774; PMCID: PMC5780224.
  21. Yamamoto T, Byun J, Zhai P, Ikeda Y, Oka S, Sadoshima J. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One. 2014 Jun 6;9(6):e98972. doi: 10.1371/journal.pone.0098972. PMID: 24905194; PMCID: PMC4048236.
  22. Carling D. AMPK signalling in health and disease. Curr Opin Cell Biol. 2017 Apr;45:31-37. doi: 10.1016/j.ceb.2017.01.005. Epub 2017 Feb 21. PMID: 28232179.
  23. Boyer PD, Chance B, Ernster L, Mitchell P, Racker E, Slater EC. Oxidative phosphorylation and photophosphorylation. Annu Rev Biochem. 1977;46:955-66. doi: 10.1146/annurev.bi.46.070177.004515. PMID: 18361775.
  24. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, Zhao G, Marsh K, Kym P, Jung P, Camp HS, Frevert E. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 2006 Jun;3(6):403-16. doi: 10.1016/j.cmet.2006.05.005. PMID: 16753576.
  25. Giordanetto F, Karis D. Direct AMP-activated protein kinase activators: a review of evidence from the patent literature. Expert Opin Ther Pat. 2012 Dec;22(12):1467-77. doi: 10.1517/13543776.2012.743994. Epub 2012 Nov 8. PMID: 23136886.
  26. Xiao B, Sanders MJ, Carmena D, Bright NJ, Haire LF, Underwood E, Patel BR, Heath RB, Walker PA, Hallen S, Giordanetto F, Martin SR, Carling D, Gamblin SJ. Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017. doi: 10.1038/ncomms4017. PMID: 24352254; PMCID: PMC3905731.
  27. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018 Feb;19(2):121-135. doi: 10.1038/nrm.2017.95. Epub 2017 Oct 4. PMID: 28974774; PMCID: PMC5780224.
  28. Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol. 2011 Sep 2;13(9):1016-23. doi: 10.1038/ncb2329. PMID: 21892142; PMCID: PMC3249400.
  29. Noor HB, Mou NA, Salem L, Shimul MFA, Biswas S, Akther R, Khan S, Raihan S, Mohib MM, Sagor MAT. Anti-inflammatory Property of AMP-activated Protein Kinase. Antiinflamm Antiallergy Agents Med Chem. 2020;19(1):2-41. doi: 10.2174/1871523018666190830100022. PMID: 31530260; PMCID: PMC7460777.
  30. Russell FM, Hardie DG. AMP-Activated Protein Kinase: Do We Need Activators or Inhibitors to Treat or Prevent Cancer? Int J Mol Sci. 2020 Dec 27;22(1):186. doi: 10.3390/ijms22010186. PMID: 33375416; PMCID: PMC7795930.
  31. Wu S, Zou MH. AMPK, Mitochondrial Function, and Cardiovascular Disease. Int J Mol Sci. 2020 Jul 15;21(14):4987. doi: 10.3390/ijms21144987. PMID: 32679729; PMCID: PMC7404275.
  32. Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, O'Neill HM, Ford RJ, Palanivel R, O'Brien M, Hardie DG, Macaulay SL, Schertzer JD, Dyck JR, van Denderen BJ, Kemp BE, Steinberg GR. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013 Dec;19(12):1649-54. doi: 10.1038/nm.3372. Epub 2013 Nov 3. PMID: 24185692; PMCID: PMC4965268.
  33. Yau H, Rivera K, Lomonaco R, Cusi K. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep. 2013 Jun;13(3):329-41. doi: 10.1007/s11892-013-0378-8. PMID: 23625197.
  34. Zhang D, Wang W, Sun X, Xu D, Wang C, Zhang Q, Wang H, Luo W, Chen Y, Chen H, Liu Z. AMPK regulates autophagy by phosphorylating BECN1 at threonine 388. Autophagy. 2016 Sep;12(9):1447-59. doi: 10.1080/15548627.2016.1185576. Epub 2016 Jun 15. PMID: 27304906; PMCID: PMC5082788.
  35. Bergeron R, Ren JM, Cadman KS, Moore IK, Perret P, Pypaert M, Young LH, Semenkovich CF, Shulman GI. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1340-6. doi: 10.1152/ajpendo.2001.281.6.E1340. PMID: 11701451.
  36. Hwang JH, Kim YH, Noh JR, Choi DH, Kim KS, Lee CH. Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury. Mol Cells. 2015 Oct;38(10):843-50. doi: 10.14348/molcells.2015.0072. Epub 2015 Oct 2. PMID: 26434492; PMCID: PMC4625065.
  37. Hardie DG, Schaffer BE, Brunet A. AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs. Trends Cell Biol. 2016 Mar;26(3):190-201. doi: 10.1016/j.tcb.2015.10.013. Epub 2015 Nov 23. PMID: 26616193; PMCID: PMC5881568.
  38. Galic S, Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR, Izon D, Honeyman J, Chen ZP, van Denderen BJ, Kemp BE, Steinberg GR. Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest. 2011 Dec;121(12):4903-15. doi: 10.1172/JCI58577. Epub 2011 Nov 14. PMID: 22080866; PMCID: PMC3226000.
  39. Noor HB, Mou NA, Salem L, Shimul MFA, Biswas S, Akther R, Khan S, Raihan S, Mohib MM, Sagor MAT. Anti-inflammatory Property of AMP-activated Protein Kinase. Antiinflamm Antiallergy Agents Med Chem. 2020;19(1):2-41. doi: 10.2174/1871523018666190830100022. PMID: 31530260; PMCID: PMC7460777.
  40. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. doi: 10.1016/s0092-8674(04)00416-7. PMID: 15137942.
  41. Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14. PMID: 29249689; PMCID: PMC5842119.
  42. Kiss T, Nyúl-Tóth Á, Balasubramanian P, Tarantini S, Ahire C, Yabluchanskiy A, Csipo T, Farkas E, Wren JD, Garman L, Csiszar A, Ungvari Z. Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. Geroscience. 2020 Apr;42(2):527-546. doi: 10.1007/s11357-020-00165-5. Epub 2020 Feb 13. PMID: 32056076; PMCID: PMC7206476.
  43. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, Grant R. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One. 2011 Apr 26;6(4):e19194. doi: 10.1371/journal.pone.0019194. PMID: 21541336; PMCID: PMC3082551.
  44. Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi: 10.1371/journal.pone.0042357. Epub 2012 Jul 27. PMID: 22848760; PMCID: PMC3407129.
  45. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011. PMID: 29514064; PMCID: PMC6342515.
  46. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. PMID: 33353981; PMCID: PMC7963035.
  47. Stein LR, Imai S. The dynamic regulation of NAD metabolism in mitochondria. Trends Endocrinol Metab. 2012 Sep;23(9):420-8. doi: 10.1016/j.tem.2012.06.005. Epub 2012 Jul 21. PMID: 22819213; PMCID: PMC3683958.
  48. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29. PMID: 24786309; PMCID: PMC4112140.
  49. Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806. doi: 10.1016/j.cmet.2016.09.013. Epub 2016 Oct 27. PMID: 28068222; PMCID: PMC5668137.
  50. Tamas Kiss, Ádám Nyúl-Tóth, Priya Balasubramanian, Stefano Tarantini, Chetan Ahire, Andriy Yabluchanskiy, Tamas Csipo, Eszter Farkas, Jonathan D. Wren, Lori Garman, Anna Csiszar, Zoltan Ungvari. Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain. GeroScience. 2020;42(2):527-546. doi: 10.1007/s11357-020-00177-1.


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