Fig. 4.

SASP‐related innate immune responses. Cytoplasmic DNA‐induced cGAS‐STING innate immune pathway plays a pivotal role in SASP induction. Mechanisms underlying the senescence‐associated increase in cytoplasmic DNA include impaired nuclear membrane integrity, cytoplasmic chromatin fragment formation, de‐repression of LINE‐1, and reduced expression of DNase2 and TREX1. Extrinsic inducers of innate immune responses also contribute to the SASP. For example, gut microbiota‐derived LTA stimulates TLR2 expressed on senescent hepatic stellate cells and thereby upregulates COX2 expression, which then produces immunosuppressive PGE₂. [Colour figure can be viewed at wileyonlinelibrary.com]