Fig. 1.

Overview of senescence inducers, changes in cell physiology, and activation of the senescence-associated secretory phenotype (SASP). The senescence programme can be activated by different stress stimuli (shown in blue) such as: cytotoxic chemotherapeutic drugs, replicative stress (which occurs due to deficiencies in the DNA replication machinery or maintenance of cell cycle checkpoints), ionising radiation, oncogenic signalling, and oxidative stress. The main cellular and molecular effects are shown in red and include an expansion of the lysosomal compartment, metabolic and mitochondrial alterations, accumulation of DNA damage and rearrangement of the chromatin landscape, resistance to apoptosis, and an irreversible arrest of the cell cycle. Most senescent cells also activate a senescence-associated secretory phenotype (SASP), which is composed of growth factors, cytokines, chemokines, and metalloproteinases. Examples of common SASP factors are shown. These secreted factors can signal in an autocrine fashion to reinforce the senescence phenotype, or paracrinally with multiple effects on neighbouring cells. EGF epithelial growth factor, FGFs fibroblast growth factors, BMPs bone morphogenetic proteins, IL1 interleukin 1, IL6 interleukin 6, IL8 interleukin 8, CCL2 C–C motif chemokine ligand 2, MMP2 matrix metallopeptidase 2, MMP3 matrix metallopeptidase 3