Cellular Senescence and Inflammaging in Prostate Cancer: Aging Microenvironment, Immune Remodeling, and Therapeutic Implications

Prostate cancer is strongly associated with aging, but the biological mechanisms linking aging to tumor progression remain incompletely defined. Beyond accumulated genetic alterations, aging reshapes the prostate tissue microenvironment through cellular senescence, chronic low-grade inflammation, immune dysfunction, stromal remodeling, metabolic stress, and impaired tissue repair. These processes contribute to inflammaging, a persistent inflammatory state that may create a permissive microenvironment for prostate tumor initiation, progression, immune evasion, and treatment resistance. Senescent epithelial and stromal cells can secrete cytokines, chemokines, growth factors, matrix-remodeling enzymes, and extracellular vesicles through the senescence-associated secretory phenotype (SASP). In parallel, immune aging alters T-cell subsets, myeloid cells, macrophages, and other immune populations, affecting anti-tumor surveillance and tumor-promoting inflammation. This review summarizes current knowledge of cellular senescence and inflammaging in prostate cancer, with emphasis on SASP, Th17/Treg imbalance, IL-17/IL-23-related inflammatory signaling, myeloid remodeling, stromal aging, metabolic stress, and immune–stromal–epithelial crosstalk. We also discuss how aging-associated inflammatory networks may influence tumor progression, therapeutic response, and emerging opportunities for cytokine modulation, senescence-directed therapy, metabolic intervention, and biomarker-guided approaches. Understanding the aging prostate microenvironment may reveal new strategies to prevent or delay aggressive prostate cancer progression in older men.