The senescence ecosystem in genomic and epigenomic evolution during inflammation-associated carcinogenesis.

Chronic inflammation promotes cancer through repeated tissue injury, incomplete repair, and selection of adapted cell clones, but the mechanisms that convert a reversible inflammatory response into a tumor-permissive state remain incompletely defined. Cellular senescence provides a plausible, context-dependent component of this process. Although senescence initially limits expansion of damaged cells, persistent senescent cells and their niches can alter DNA-damage exposure, epigenomic state, immune surveillance, stromal mechanics, vascular function, and the fitness landscape encountered by neighboring clones. This Review links DNA damage, replication stress, telomere dysfunction, chromosomal instability, senescence escape, DNA methylation, chromatin remodeling, and inflammatory memory with spatially and temporally structured clonal selection. We compare organ-specific trajectories in inflammatory bowel disease, chronic liver disease, chronic pancreatitis, Helicobacter pylori gastritis, and chronic obstructive pulmonary disease, and appraise evidence from longitudinal human studies, cross-sectional observations, animal perturbations, and in vitro experiments. We also evaluate biomarkers and senotherapies according to their current evidence level. Finally, we present the Senescence Ecosystem Framework as a set of testable propositions concerning where senescent cells reside, how their functions change over time, and whether their niches alter the expansion of genetically or epigenetically altered clones. This framework extends the senescence-associated secretory phenotype (SASP) and tumor-microenvironment models without treating senescence as a proven independent cause of malignant evolution.