Figure 3.

Schematic illustration of YAP/TAZ in aging and senescence. Studies revealed that alterations in biophysical ECM features and integrin–ECM interactions may lead to altered mechanotransduction and reduced YAP/TAZ activity. This YAP deficiency induces the senescence-associated secretory phenotype (SASP), which is based on the secretion of pro-inflammatory molecules and creates an inflammatory cell environment with the involvement of the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) signaling cascade. STING thereby functions as a sensor for cytosolic DNA, which binds to and is activated by cGAS. Following its activation, STING induces the synthesis of interferon type I (IFNI) and contributes to the formation of the SASP phenotype. Lamin B1 (LMNB1) is important for nuclear integrity and has been discovered as a reliable marker of senescence. There is a direct connection between YAP/TAZ and LMNB1 since this lamin was almost undetectable in YAP/TAZ-depleted cells. ARPC2/3, which codes for the actin-related protein 2/3 complex (ACTR2 = ARPC2/3) involved in actin polymerization, was also downregulated in YAP/TAZ-depleted cells, and this decrease in ARPC2/3 led to a loss of the actin cap with the consequent bulging of the nuclear envelope and its increasing wrinkling and cytosolic DNA release. This means that ARPC2/3 and LMNB1 are further target genes of YAP/TAZ. The schematic was created with BioRender.com.