“…The complexity of the SASP, typically appraised by a list of secreted proteins, has been largely underestimated, as a small handful of factors cannot explain this varying phenotype. In fact, many studies reported that expression of the SASP is subject to regulation by an intricate but well-ordered signaling network, which comprises but is not limited to ATM, γH2AX, Zscan4, TAK1, p38, MAPK, mTOR, IL-1α, NF-κB, c/EBPβ, JAK2/STAT3 and GATA4 (Borghesan et al, 2020;Hernandez-Segura et al, 2018;Song et al, 2020a;Song et al, 2020b;Sun et al, 2018b;Sun et al, 2022b). Despite these advances, increasing lines of data suggest that SASP regulation is indeed multilayered, including contributions from pre-transcriptional signaling cascades such as the cGAS-STING pathway, epigenetic factors governing DNA and histone modifications as well as the super-enhancer landscape in senescent cells (Criscione et al, 2016a;Glück et al, 2017;Sati et al, 2020;Tasdemir et al, 2016;Yang et al, 2017;Zhang et al, 2021a).…”