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Jan 7, 2025
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Jan 7, 2025
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Abstract

The most often given oral hypoglycaemic drug for type 2 diabetes globally is metformin, a biguanide anti-diabetic drug that has been around for more than 30 years. Its mode of action wasn't understood till a few years ago. However, it was recently found that through an increased tissue glucose uptake by a transporter-linked system, is now connected to better peripheral sensitivity to insulin. Although it is clear that not all possible effects of metformin use have been identified yet, it is feasible that metformin will become a cornerstone treatment for illnesses associated with ageing and other related conditions such as cancer and neurological diseases in humans. Despite the fact that not everyone using metformin experiences the same advantages, some people do have negative effects. Therefore, it is essential to fully comprehend the mechanism and all potential side effects of this medication. Therefore, this study offers a summary of current advances in metformin's impact on ageing and illnesses linked to it.

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Hypoglycemic metformin ageing insulin

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Kavinraja. A, Aswin. R, & Kameswaran. R. (2025). Metformin: A revolutionary drug that halts the aging process, keeping you youthful indefinitely. International Journal of Research in Pharmacology & Pharmacotherapeutics, 14(1), 11-15. Retrieved from https://ijrpp.com/ijrpp/article/view/610
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References

  1. 1. Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571(7764):183-192. doi:10.1038/s41586-019-1365-2.
  2. 2. Kubben N, Misteli T. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases. Nat Rev Mol Cell Biol. 2017;18(10):595-609. doi:10.1038/nrm.2017.68.
  3. 3. Goodell MA, Rando TA. Stem cells and healthy aging. Science. 2015;350(6265):1199-1204. doi:10.1126/science.aab3388.
  4. 4. Lublóy Á. Medical crowdfunding in a healthcare system with universal coverage: an exploratory study. BMC Public Health. 2020;20(1):1672. Published 2020 Nov 9. doi:10.1186/s12889-020-09693-3.
  5. 5. Trevisan K, Cristina-Pereira R, Silva-Amaral D, Aversi-Ferreira TA. Theories of Aging and the Prevalence of Alzheimer's Disease. Biomed Res Int. 2019;2019:9171424. Published 2019 Jun 16. doi:10.1155/2019/9171424.
  6. 6. Donato AJ, Machin DR, Lesniewski LA. Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease. Circ Res. 2018;123(7):825-848. doi:10.1161/CIRCRESAHA.118.312563.
  7. 7. Faget DV, Ren Q, Stewart SA. Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer. 2019;19(8):439-453. doi:10.1038/s41568-019-0156-2
  8. 8. Hartley AV, Martin M, Lu T. Aging: Cancer - an unlikely couple. Aging (Albany NY). 2017;9(9):1949-1950. doi:10.18632/aging.101295.
  9. 9. Grote C, Reinhardt D, Zhang M, Wang J. Regulatory mechanisms and clinical manifestations of musculoskeletal aging. J Orthop Res. 2019;37(7):1475-1488. doi:10.1002/jor.24292.
  10. 10. Musci RV, Walsh MA, Konopka AR, et al. The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging. Front Physiol. 2020;11:571372. Published 2020 Oct 29. doi:10.3389/fphys.2020.571372.
  11. 11. Gaffney CJ, Pollard A, Barratt TF, Constantin-Teodosiu D, Greenhaff PL, Szewczyk NJ. Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans. Aging (Albany NY). 2018;10(11):3382-3396. doi:10.18632/aging.101654.
  12. 12. Shaw RJ, Lamia KA, Vasquez D, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310(5754):1642-1646. doi:10.1126/science.1120781.
  13. 13. Sui X, Xu Y, Wang X, Han W, Pan H, Xiao M. Metformin: A Novel but Controversial Drug in Cancer Prevention and Treatment. Mol Pharm. 2015;12(11):3783-3791. doi:10.1021/acs.molpharmaceut.5b00577.
  14. 14. Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010;3(11):1451-1461. doi:10.1158/1940-6207.CAPR-10-0157.
  15. 15. Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J. 2015;471(3):307-322. doi:10.1042/BJ20150497.
  16. 16. Podhorecka M, Ibanez B, Dmoszyńska A. Metformin - its potential anti-cancer and anti-aging effects. Postepy Hig Med Dosw (Online). 2017;71(0):170-175. Published 2017 Mar 2. doi:10.5604/01.3001.0010.3801.
  17. 17. Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000;49(12):2063-2069. doi:10.2337/diabetes.49.12.2063.
  18. 18. Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J. 2015;471(3):307-322. doi:10.1042/BJ20150497.
  19. 19. Yamaguchi O, Otsu K. Role of autophagy in aging. J Cardiovasc Pharmacol. 2012;60(3):242-247. doi:10.1097/FJC.0b013e31824cc31c.
  20. 20. Hu F, Liu F. Mitochondrial stress: a bridge between mitochondrial dysfunction and metabolic diseases?. Cell Signal. 2011;23(10):1528-1533. doi:10.1016/j.cellsig.2011.05.008.
  21. 21. McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006;16(14):R551-R560. doi:10.1016/j.cub.2006.06.054.
  22. 22. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359-407. doi:10.1146/annurev.genet.39.110304.095751.
  23. 23. Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002;51(7):2074-2081. doi:10.2337/diabetes.51.7.2074.
  24. 24. Boyle JG, Logan PJ, Jones GC, et al. AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study. Diabetologia. 2011;54(7):1799-1809. doi:10.1007/s00125-011-2126-4.
  25. 25. Sun EW, Martin AM, Wattchow DA, et al. Metformin Triggers PYY Secretion in Human Gut Mucosa. J Clin Endocrinol Metab. 2019;104(7):2668-2674. doi:10.1210/jc.2018-02460.
  26. 26. Vara-Ciruelos D, Russell FM, Hardie DG. The strange case of AMPK and cancer: Dr Jekyll or Mr Hyde? †. Open Biol. 2019;9(7):190099. doi:10.1098/rsob.190099.
  27. 27. Lin SC, Hardie DG. AMPK: Sensing Glucose as well as Cellular Energy Status. Cell Metab. 2018;27(2):299-313. doi:10.1016/j.cmet.2017.10.009.
  28. 28. Schlender L, Martinez YV, Adeniji C, et al. Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing. BMC Geriatr. 2017;17(Suppl 1):227. Published 2017 Oct 16. doi:10.1186/s12877-017-0574-5.
  29. 29. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016;23(6):1060-1065. doi:10.1016/j.cmet.2016.05.011.
  30. 30. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016;23(6):1060-1065. doi:10.1016/j.cmet.2016.05.011.
  31. 31. Halicka HD, Zhao H, Li J, et al. Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. Aging (Albany NY). 2012;4(12):952-965. doi:10.18632/aging.100521.
  32. 32. Anisimov VN, Bartke A. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol. 2013;87(3):201-223. doi:10.1016/j.critrevonc.2013.01.005.
  33. 33. Bartke A. Growth hormone, insulin and aging: the benefits of endocrine defects. Exp Gerontol. 2011;46(2-3):108-111. doi:10.1016/j.exger.2010.08.020.
  34. 34. Barzilai N, Huffman DM, Muzumdar RH, Bartke A. The critical role of metabolic pathways in aging. Diabetes. 2012;61(6):1315-1322. doi:10.2337/db11-1300.
  35. 35. Bartke A. Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc Lond B Biol Sci. 2011;366(1561):28-34. doi:10.1098/rstb.2010.0281.
  36. 36. Bartke A, Brown-Borg H. Life extension in the dwarf mouse. Curr Top Dev Biol. 2004;63:189-225. doi:10.1016/S0070-2153(04)63006-7.
  37. 37. Blagosklonny MV. Increasing healthy lifespan by suppressing aging in our lifetime: preliminary proposal. Cell Cycle. 2010;9(24):4788-4794. doi:10.4161/cc.9.24.14360.
  38. 38. Darzynkiewicz Z, Zhao H, Halicka HD, et al. In search of antiaging modalities: evaluation of mTOR- and ROS/DNA damage-signaling by cytometry. Cytometry A. 2014;85(5):386-399. doi:10.1002/cyto.a.22452
  39. 39. Onken B, Driscoll M. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS One. 2010;5(1):e8758. Published 2010 Jan 18. doi:10.1371/journal.pone.0008758.
  40. 40. Anisimov VN, Bartke A. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol. 2013;87(3):201-223. doi:10.1016/j.critrevonc.2013.01.005.
  41. 41. Anisimov VN. Metformin: do we finally have an anti-aging drug?. Cell Cycle. 2013;12(22):3483-3489. doi:10.4161/cc.26928.
  42. 42. Morselli E, Galluzzi L, Kepp O, et al. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol. Aging (Albany NY). 2009;1(12):961-970. Published 2009 Dec 23. doi:10.18632/aging.100110.
  43. 43. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-695. doi:10.1016/j.cell.2011.07.030.
  44. 44. Morselli E, Maiuri MC, Markaki M, et al. Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2010;1(1):e10. doi:10.1038/cddis.2009.8.
  45. 45. Sauve AA, Wolberger C, Schramm VL, Boeke JD. The biochemistry of sirtuins. Annu Rev Biochem. 2006;75:435-465. doi:10.1146/annurev.biochem.74.082803.133500.
  46. 46. Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging (Albany NY). 2011;3(8):716-732. doi:10.18632/aging.100361.