Figure 1.

Cellular senescence as an alternative pathway to apoptosis after accumulated DNA damage. When accumulated DNA damage occurs, the affected cells can repair the DNA damage to continue their programmed functions or, when their repair mechanisms cannot restore the integrity of damaged DNA, cells can initiate either the apoptosis program or senescence program. In fact, cell senescence is an alternative fate to apoptosis that prioritizes cell survival instead of cell function. The programming of the common phenotype among senescent cells is initiated by the DNA damage response (DDR) that leads to the arrest of the cell cycle, in order to avoid the replication of the defective cell. Then, cells present an increase in the activity of senescence-associated-β-galactosidase (SA-βgal), which is linked to lysosomal failure and potential autophagy alterations; however, this link remains unclear. In turn, the defective autophagy observed in senescent cells can lead to the accumulation of dysfunctional mitochondria and consequently to the increase of the production of reactive oxygen species (ROS). Besides, these cells can acquire a senescence-associated secretory phenotype (SASP), producing increased levels of cytokines, chemokines, growth factors, and proteases (Created with BioRender.com).