The study investigates the mechanism by which interleukin-6 (IL-6) sustains cell-autonomous senescence through an intracrine pathway. IL-6, a key factor in the Senescence-Associated Secretory Phenotype (SASP), has both pro-senescence and pro-proliferative effects. The research reveals that IL-6's senescent action does not involve secretion or receptor interaction but is amplified through intracellular signaling. IL-6 interacts with its intracellular receptor, leading to cGAS-STING activation and NFκB activation, which contributes to cell-autonomous senescence and impacts tumor growth control. Inhibition of IL-6 in somatotrophic senescent cells transforms them into highly tumorigenic in NOD/SCID mice, while re-expression of IL-6 restores senescence control. The study also demonstrates that IL-6's intracellular signaling is critical in therapy-induced senescence models, such as glioblastoma, pulmonary, and melanoma cells. These findings add a new layer of complexity to the understanding of SASP factors and their role in cellular senescence and tumorigenesis.The study investigates the mechanism by which interleukin-6 (IL-6) sustains cell-autonomous senescence through an intracrine pathway. IL-6, a key factor in the Senescence-Associated Secretory Phenotype (SASP), has both pro-senescence and pro-proliferative effects. The research reveals that IL-6's senescent action does not involve secretion or receptor interaction but is amplified through intracellular signaling. IL-6 interacts with its intracellular receptor, leading to cGAS-STING activation and NFκB activation, which contributes to cell-autonomous senescence and impacts tumor growth control. Inhibition of IL-6 in somatotrophic senescent cells transforms them into highly tumorigenic in NOD/SCID mice, while re-expression of IL-6 restores senescence control. The study also demonstrates that IL-6's intracellular signaling is critical in therapy-induced senescence models, such as glioblastoma, pulmonary, and melanoma cells. These findings add a new layer of complexity to the understanding of SASP factors and their role in cellular senescence and tumorigenesis.