Introduction to Senescence-Associated Secretory Phenotype (SASP)

An aspect of cellular senescence is the senescence-associated secretory phenotype (SASP), which is defined by the robust release of a heterogeneous mixture of pro-inflammatory cytokines (e.g., IL-6, IL-1β) and chemokines (e.g., CXCL8, CCL2). SASP is induced to a great extent as a result of a large number of stresses leading to senescence such as oxidative damage, sustained DNA damage response (DDR), telomere erosion, and oncogene activation. It also exerts pleiotropic effects on the tissue microenvironment. The persistent and sustained activation of the SASP signaling facilitates tissue dysfunction, inflammation, progression of tumors, and pathophysiology of various age-related conditions, such as cancer, fibrosis, and neurodegenerative disorders, among others. On the other hand, SASP signaling is transient and stimulates tumor suppression, tissue repair, and wound healing with the help of immune cells’ recruitment and remodeling functions. In conjunction with the chromatin-level and epigenetic processes that modify SASP heterogeneity among the cell types and circumstances, all integrated signaling networks, such as NF-κB, C/EBPβ, p38 MAPK, and mTOR, tightly regulate expression of the SASP components. Senolytics targeting specifically senescent cells and senomorphics that decrease the factors of SASP without killing the cells are two applied treatment mechanisms aimed at mitigating the adverse effects of SASP. Nevertheless, issues related to off-target toxicity, selectivity, and functional senescence duality remain barriers to practical translation. Typing out cell-specific SASP profiles, discovering new upstream regulators like noncoding RNAs and metabolic mediators, and producing SASP-originated biomarkers for diagnostic and therapeutic functions would be the focus of future studies. This chapter underlines the growing importance of SASP as the target of regenerative medicine and age-related diseases. It provides detailed information regarding the molecular composition, regulatory network, and context-specific functions in physiology and diseases.