ABSTRACT
The Senescence-Associated Secretory Phenotype (SASP), characterized by the upregulation of inflammatory cytokines, is triggered during senescence by anti-proliferation stresses, such as replicative exhaustion and centrosome amplification. Previously, we have discovered that centrosome amplification activates a non-canonical SASP that is dominated by HIF-1α-induced inflammatory cytokines instead of the NFκb activation in canonical SASP. HIF-1α is not only activated in centrosome amplification, oncogene, and gamma-irradiation-induced senescence1 but also induced in replicative exhaustion-induced senescence. Another major consequence of centrosome amplification is micronuclei generation from chromosome missegregation. The micronuclei could have triggered SASP by activating cGAS/Sting innate immune response2. However, it has been shown that micronuclei from chromosome missegregation fail to activate cGAS/Sting-mediated innate immune response3–5. Indeed, here we further demonstrate that moderate chromosome missegregation by centrosome amplification or mitotic kinase monopolar spindle 1 inhibition, which is known to generate micronuclei, fails to induce senescence and cGAS-mediated interferon response. In summary, we provide evidence that the Senescence-Associated-Secretory Phenotype constitutes hypoxia-inducible factor-alpha activation, independent of chromosome missegregation triggering cGAS-mediated innate immune interferon response.
Competing Interest Statement
The authors have declared no competing interest.
