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Cell-fate partitioning after senescence induction: modeling SASP-driven escape trajectories

#CellularSenescence #SASP #CellCycleReentry #SenescenceEscape #TumorSuppression #NFkBSignaling #SystemsBiology #ComputationalCellBiology
Cell-fate partitioning after senescence induction: modeling SASP-driven escape trajectories I am sharing a data visualization that formalizes an increasingly discussed but underappreciated phenomenon in the senescence literature: the capacity of a subpopulation of arrested cells to re-enter the cell cycle rather than remaining stably arrested or undergoing clearance. The figure, titled "Cell-fate partitioning after senescence induction," uses a bidirectional flow trajectory (streamgraph-style stacked area) to render the temporal redistribution of an initial senescent-induced cohort across three terminal or quasi-terminal states over a 30-day window: stable arrest, apoptotic clearance, and senescence escape. The subtitle emphasizes that these are simulated dynamics, not empirical measurements; the parameterization is literature-grounded, calibrated to reported ranges for p16INK4a/p21CIP1 durability, SASP factor accumulation kinetics, and escape frequencies observed in oncogene- and therapy-induced senescence models. The streamgraph format is deliberate. Because escape is a flux phenomenon rather than a static endpoint, the bidirectional banding captures net transitions between compartments, including the small but non-negligible reflux from a metastable arrested state back into proliferation. The simulation encodes a positive-feedback term whereby paracrine and autocrine SASP components — principally IL-6, IL-8, and other NF-κB-dependent secreted factors — lower the effective barrier to CDK reactivation in cells with attenuated tumor-suppressor signaling. The escape band consequently widens after the SASP matures, roughly days 8 to 15 in this parameterization, consistent with the delayed secretory phenotype. I would welcome critique on the transition-rate assumptions, particularly the coupling coefficient between SASP intensity and escape probability, which remains poorly constrained empirically.
September 18, 2026 at 5:01 PM