Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents

Cellular senescence denotes an irreversible cell-cycle arrest implicated in or-ganismal aging and age-related disorders, distinguished by the Senescence-Associated Secretory Phenotype (SASP). SASP manifests the capacity of senescent cells to secrete a broad array of bioactive molecules-cytokines, chemokines, proteases, growth factors, and bioactive lipids that orchestrate diverse extracellular functions across pathological contexts. Senomorphic strategies that selectively suppress SASP have emerged as promising therapeutic avenues for mitigating aging-related pathologies. Natural prod-ucts, including polyphenols, flavonoids, and alkaloids, possess inherent antioxidant and anti-inflammatory properties and have demonstrated significant efficacy in modulating SASP in both aging and diseases. This review, for the first time, systematically consoli-dates current investigations into natural compounds targeting SASP, providing a com-prehensive analysis of their underlying mechanisms, therapeutic potential, and pro-spects for clinical translation in non-cancerous age-related diseases. We delineate how SASP is initiated, its composition, pathophysiological roles, and how natural com-pounds modulate it, thereby establishing a foundation for future research and therapeu-tic development in ageing intervention.