Hormesis as a universal cellular strategy for growth.

Our review synthesizes a vast and dispersed literature to demonstrate that subtoxic doses of structurally diverse chemicals can induce a conserved growth-stimulatory (hormetic) response across bacterial, microalgal, plant, and mammalian cells. Stimulation is concentration- and exposure-time-dependent, with higher concentrations inhibiting growth. In eukaryotic models, moderate ROS signaling and activation of DNA-PKcs/Akt, ERK1/2, PI3K/AKT, mTOR, or AURKA accompany growth stimulation, with Cyclin D-CDK4 promoting G1/S transition in mammalian cells. The proliferative DNA-PKcs/Akt response is observed in human hepatic cells, while bacterial examples involve LuxR-dependent signaling and fatty acid β-oxidation. Metabolism rewires, with some microalgae enhancing glycolysis and Krebs cycling, whereas other photosynthetic microorganisms reroute photosynthetic carbon toward lipid or starch storage while downregulating selected carbohydrate-catabolic proteins. Nrf2-driven antioxidants in mammalian cells, carotenoids, and detoxifying enzymes are upregulated, establishing a preconditioned state that can attenuate apoptosis upon subsequent challenge. Within the Catabolic-Anabolic Cycling Hormesis (CACH) model, some time-dependent responses are consistent with an anabolic overshoot following a transient catabolic decline (ATP depletion). This anabolic reprogramming accompanies biofilm formation, altered motility, and, in neoplastic cells, anchorage-independent growth. Thus, cell proliferation is a metabolic strategy shaped by adversity, with functional consequences that depend on cellular context and the endpoint assessed.