Figure 2.

Metformin maintenance of the epigenetic landscape. The height and steepness of hills between two valleys determine, at least in part, the ability of the epigenome to modulate phenotypic plasticity and canalization during differentiation. Metformin might prevent the undesirable interconversion of neighboring cellular epistates occupying adjacent valleys by fine-tuning both the provision of specific epi-metabolites and the activation status of chromatin-modifying enzymes that specify a given cell type, i.e., two key shapers of the Waddington’s epigenomic landscape. As a consequence, metformin might halt the erosion of the epigenetic landscape and delay age-associated epigenetic drift, i.e., the gradual decrease of global DNA methylation leading to the alteration of epigenetic patterns.