Figure 3 .

The DDR response is triggered as a response to stress (irradiation, ROS), DNA damage or telomere uncapping, leading to the senescent state. Changes of nuclear localization of telomeres disrupt their maintenance and homeostasis. Nuclear cGAS accumulates at LINE-1 s and centromeres [123], and it interferes with DNA repair [124, 125]. SIRT-6 sequestration to DNA damage sites impacts LINE-1 expression [120]. These changes lead to nuclear blebbing and the expulsion of CFFs [53], which elicit an interferon response via the cGAS-STING pathway, leading to chronic inflammation [58].