Figure 12. Potential role of autophagy in conferring “senolytic” activity. Autophagic cells have an increased tendency to become senescent. Mechanistically, autophagic cells accumulate large numbers of lysosomes and auto-phagosomes. These organelles contain high levels of proteases, such as cathepsins (B, S and L). Interestingly, it has been previously demonstrated that lysosomes in authophagic cells can become “leaky” due to an acute stress, ultimately resulting in stress-induced senescence (SIS). As a consequence, cathepsins leak into the cytoplasm where they can then cleave sirtuin family members (e.g., SIRT1), paving the way for the onset of senescence. Here, we show that a weak autophagy inducer, Azithromycin (AZ), selectively targets senescent cells. We speculate that the weak induction of autophagy in senescent cells can result in cell death.