Figure 2. A time-gated model for the senescence-associated secretory phenotype (SASP)-mediated biological activities of cellular senescence.

The SASP can have a wide range of effects in the surrounding microenvironment, including matrix remodelling, mitogenic signalling, clearance regulation, inflammation, immune modulation, cell proliferation, migration, differentiation and plasticity, as well as vascularization. Depending on the time duration of the senescence programme and the associated SASP response, effects can be beneficial or detrimental. Anti-fibrotic and anti-inflammatory effects are normally correlated to a transient SASP and favour tissue repair and regeneration. A short-term SASP also favours immune-mediated clearance of SCs in order to avoid their accumulation and persistence. Likewise, a transient senescence profile is fundamental for tissue patterning during development. In contrast, long-lasting SASP responses have detrimental pro-fibrotic and pro-inflammatory effects on the microenvironment. Therefore, the persistent accumulation of SCs leads to tissue dysfunction and is associated with chronic inflammation and a broad spectrum of aging-related diseases. Persistent senescence responses can also deplete stem cell progenitor pools, impairing the repair/regenerative capability of affected tissues. In turn, the role of the SASP in cancer is more ambiguous than the rest, as SCs can both promote tumour suppression and tumour progression/invasiveness. However, current knowledge suggests that the SASP suppresses tumour growth in early stages, while supplying pro-tumourigenic chronic inflammatory environments in later stages.