De Haes, Wouter et al. (2015) International Worm Meeting "PRDX-2 mediates lifespan extension by metformin."

Temmerman, Liesbet, De Haes, Wouter, Depuydt, Geert, Van Assche, Roel, Frooninckx, Lotte, Billen, Johan, Braeckman, Bart P., Schoofs, Liliane, Smolders, Arne

[International Worm Meeting, 2015]

Metformin, the most powerful anti-diabetic drug on the market today, is thought to possess general health-promoting properties. Via an integrative approach using proteomic, bioinformatic, biochemical and phenotypic techniques and the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance.We could show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species (ROS) eventually increases overall life expectancy. We were further able to show that the peroxiredoxin PRDX-2 translates the ROS signal into a beneficial signal of the mitohormetic pathway and propose that this mechanism might underlie a general principle of pro-longevity signaling.