Figure 3. Chronic exposure to metformin accelerates the onset of replicative senescence in human [WI-38 and BJ-1] fibroblast cultures confirmed by senescence-associated β-galactosidase (SA-β-gal) staining (A). Chronic exposure to metformin sensitizes [MCF-7] cancer cells to the senescence program activated by the DNA-damaging drug doxorubicin (B). Chronic exposure to metformin transcriptionally activates a senescence-associated secretory phenotype (SASP) or senescence messaging secretome (SMS) involving the production of factors that reinforce the senescence arrest, alter the surrounding microenvironment, and trigger immune surveillance of the senescent cells.