Research Paper Volume 10, Issue 11 pp 3294—3307

Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts

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.