METFORMIN PROTECTS AGAINST IRON OVERLOAD THROUGH SKN-1 IN Caenorhabditis elegans

Iron (Fe) is an essential transition metal that participates in several biochemical processes necessary for life. However, increased intracellular levels of Fe cause toxicity. In the nematode Caenorhabditis elegans, increased Fe levels decrease survival rate, as well as promote aging-related fragility, which has been associated to ferroptosis (iron-dependent cell death). Metformin, a biguanide antidiabetic drug used worldwide for the treatment of Type II Diabetes Mellitus, is capable of increasing the longevity of C. elegans by positive modulation of the SKN-1 gene (NRF-2 orthologue in mammals), which is important for (i) protecting against ferroptotic mortality, (ii) decreasing ROS levels and (iii) directly or indirectly regulating the metabolism of GSH, GPx4 and iron.