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

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.