Metformin & Aging
Presentation by: Kritika Pathak
Reviewed by: Ben Kronz
The number of people aged 65 or older is projected to grow to nearly 1.5 billion in 2050 which would add up to 16% of the total world population. Chronic illnesses related to this unprecedented aging of humans is a global challenge that poses a risk to handicap world economies and deteriorate the quality of life. Efforts are now underway to classify aging as a disease and target it as a whole instead of devising treatments for different age-related diseases individually. Metformin, a biguanide, commonly used in the management of Type 2 Diabetes is now known to retard aging and modulate key processes involved in the pathogenesis of various age-related conditions such as cardiovascular diseases, stroke, cancer, autoimmune diseases, neurocognitive disorders, etc which cannot be attributed to its effect on glucose metabolism alone. With a high therapeutic window and a low cost, Metformin is currently one of the best candidates to target the biology of aging. How Metformin brings about its effects is still controversial as novel pathways continue to be discovered.
Further studies:
● Validate its effect on various age-related conditions by large prospective, randomized
controlled trials in a nondiabetic population
● Evaluate its effect on longevity by assessing various biomarkers of aging
● Explore the response of metformin as a monotherapy and in combination with lifestyle
interventions such as exercise and calorie restriction
References:
Bannister, C. A., Holden, S. E., Jenkins-Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., Mukherjee, J., & Currie, C. J. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes, Obesity and Metabolism, 16(11), 1165–1173. https://doi.org/10.1111/dom.12354
Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016). Metformin as a Tool to Target Aging. Cell metabolism, 23(6), 1060–1065. https://doi.org/10.1016/j.cmet.2016.05.011
Campbell, J. M., Bellman, S. M., Stephenson, M. D., & Lisy., K. (2017). Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing Research Reviews, 40, 31–44. https://doi.org/10.1016/j.arr.2017.08.003
Database resources of the National Center for Biotechnology Information. (2014). Nucleic Acids Research, 43(D1), D6–D17. https://doi.org/10.1093/nar/gku1130)
Diabetes Prevention Program (DPP) Research Group (2002). The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes care, 25(12), 2165–2171. https://doi.org/10.2337/diacare.25.12.2165
Gandini, S., Puntoni, M., Heckman-Stoddard, B. M., Dunn, B. K., Ford, L., DeCensi, A., & Szabo, E. (2014). Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders. Cancer Prevention Research, 7(9), 867–885. https://doi.org/10.1158/1940-6207.capr-13-0424
Liu, Y., Weng, W., Gao, R., & Liu, Y. (2019). New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach. Oxidative Medicine and Cellular Longevity, 2019, 1–25. https://doi.org/10.1155/2019/4598167
Lv, Z., & Guo, Y. (2020). Metformin and Its Benefits for Various Diseases. Frontiers in Endocrinology, 11, https://doi.org/10.3389/fendo.2020.00191
Ng, T. P., Feng, L., Yap, K. B., Lee, T. S., Tan, C. H., & Winblad, B. (2014). Long-term metformin usage and cognitive function among older adults with diabetes. Journal of Alzheimer's disease : JAD, 41(1), 61–68. https://doi.org/10.3233/JAD-131901
Stallone, G., Infante, B., Prisciandaro, C., & Grandaliano, G. (2019). mTOR and Aging: An Old Fashioned Dress. International Journal of Molecular Sciences, 20(11), 2774. doi:10.3390/ijms20112774
Summary of the effects of metformin supplementation in invertebrate (Caenorhabditis elegans and Drosophila melanogaster) and vertebrate models (rodents, mainly mice)
TAME - Targeting Aging with Metformin. (n.d.). American Federation for Aging Research. https://www.afar.org/tame-trial (accessed on August 8 2020)
Ursini, F., Russo, E., Pellino, G., D’Angelo, S., Chiaravalloti, A., De Sarro, G., Manfredini, R., & De Giorgio, R. (2018). Metformin and Autoimmunity: A New Deal of an Old Drug. Frontiers in Immunology, 9, 231–300. https://doi.org/10.3389/fimmu.2018.01236
World Population Prospects 2019: Highlights (ST/ESA/SER.A/423). Available at https://population.un.org/wpp/Publications/Files/WPP2019_Highlights.pdf