The ability of metformin to directly interact with TGF-β1, thereby blocking its binding to TβRII and resulting in impaired downstream signaling (12), is another example of how metformin might exert pleiotropic effects on numerous (TGF-β1 hyperfunction-associated) aging diseases such as organ fibrosis and cancer, without necessarily involving changes in cellular bioenergetics. This evidence concerns the gene TGFB1 and cancer.