Aging is a time-dependent process, affecting cellular homeostasis and tissue function. It also enhances the risk of many non-communicable diseases. With regard to this, continuous efforts are being made to find therapeutic measures to improve quality of life and delay cellular aging. Of various agents in consideration, metformin has garnered significant attention as the beneficial health effects of this drug go beyond its anti-hyperglycemic properties. One such effect of great interest is its geronto-protection capability. Growing evidence indicates that administration of metformin in experimental models increases life expectancy and enhances the quality of life.¹

Multiple cellular effects of metformin may be responsible for its action on metabolism as well as aging. Under different scenarios, these effects may be mediated by molecular targets as disparate as mitochondrial complex I, mitochondrial glycerol-3-phosphate dehydrogenase, and the H3K27me3 demethylase KDM6A/UTX.² Moreover, various pathways may underline its anti-aging actions, including the AMPK, mTORC1, FOXO, SIRT1,NF.kB, and DICER1 pathways. Furthermore, investigators havealso highlighted the possibility of gut microbiome involvement in these processes.¹

Accumulating data from preclinical models and humans support beneficial effects of this drug in reducing the risk of aging-related diseases, such as cancer and neurodegeneration. A study on Caenorhabditis elegans showed that metformin is likely to prolong its lifespan through direct action on lysosomes. Another study demonstrated that metformin slows aging of C. elegans by metabolic modulation of E. coli food source. Besides, molecular analyses of septuagenarians have shown that metformin therapy displays metabolic as well as non-metabolic effects consistent with multiple effects on aging.²

References

1. Torres W, Nava M, Nestor Galbán N, et al. Anti-Aging Effect of Metformin: A Molecular and Therapeutical Perspective. Curr Pharm Des. 2020;26(35):4496-4508.
2. Soukas AA, Hao H, Wu L. Metformin as Anti-Aging Therapy: Is It for Everyone?. Trends EndocrinolMetab. 2019;30(10):745-755.