Natural products targeting cytokine-regulated SASP inflammation networks in Ovarian cancer: Implications on immune escape and molecular resistance.

Ovarian cancer (OC) is one of the most lethal gynecological malignancies, with incidence and mortality rates increasing markedly among women aged 65 years and older. Aging-associated biological alterations, including genomic instability, telomere attrition, oxidative stress, mitochondrial dysfunction, and chronic inflammation, contribute to ovarian carcinogenesis and influence responses to chemotherapy, PARP inhibitors, and immune checkpoint blockade. A central feature linking aging and OC progression is cellular senescence, a state of irreversible growth arrest accompanied by the development of SASP. SASP comprises a complex network of pro-inflammatory cytokines, chemokines, growth factors, and matrix-remodelling enzymes that reshape the tumor microenvironment. In OC, SASP-mediated cytokine signalling promotes epithelial-to-mesenchymal transition, angiogenesis, extracellular matrix remodelling, immune evasion, and therapeutic resistance. Furthermore, SASP-driven reprogramming of immune cells establishes an immunosuppressive microenvironment that facilitates tumor progression and limits treatment efficacy. Consequently, cytokine-regulated SASP networks have emerged as promising therapeutic targets for overcoming age-associated disease progression and molecular resistance. Natural products represent a growing class of senotherapeutic agents capable of modulating senescence-associated pathways. Several phytochemicals and bioactive secondary metabolites exhibit senolytic or senostatic activities, enabling selective elimination of senescent cells or suppression of detrimental SASP signalling. Emerging nanotechnology-based delivery systems and receptor-targeted approaches further enhance the bioavailability, specificity, and therapeutic potential of these compounds. This review summarizes the role of cytokine-regulated SASP networks in OC progression, immune escape, and therapy resistance, while highlighting natural-product-derived senotherapeutics as promising strategies for precision immuno-oncology and geriatric OC management.