The Senescence-Malignancy Axis: An Inflammaging Perspective

The transition from physiological cellular senescence(definition) to malignancy is not an isolated event, but a gradual, systemic remodeling of the biological landscape orchestrated by the persistent state of inflammaging(definition). As detailed in this review, senescent populations do not remain passive. Through the chronic deployment of the senescence-associated secretory phenotype (SASP), they actively dismantle tissue architecture and convert healthy organs into a highly permissive pro-tumorigenic “soil”. This cross-talk is mediated by a complex network of signaling cascades including the IL-1 family, IL-6 and TNF-α, CXCL10 and CCL2-CCR2 chemokine axes, and MMPs. Crucially, this cellular decay is reinforced by a profound metabolic shift toward a hyper-glycolytic “metabolic SASP,” where extracellular lactate accumulation and prostaglandin synthesis permanently sustain the senescent state. Cellular senescence through the persistent accumulation of senescent cells and the accompanying age-related decline in immune surveillance drive “inflammaging”, a chronic, low-grade systemic inflammation that serves as a primary mechanistic bridge fueling the aging–cancer cycle.