SASP

The senescence-associated secretory phenotype (SASP) is the hypersecretory state of senescent cells, in which they produce and secrete a complex combination of biologically active factors. ^{[1] [2]} This secretome comprises a variety of secreted proteins including inflammatory cytokines, chemokines, matrix-remodelling factors, proteases and growth factors. ^[3] The SASP is the major mediator of the paracrine effects of senescent cells in their tissue microenvironment and of various local and systemic biological functions. ^[1]

Through SASP-mediated paracrine effects, senescent cells remodel surrounding tissues by modulating the character of adjacent stromal, immune and cancer cells. ^[3] The SASP can induce senescence in normal cells and drive secondary senescence, disrupting tissue homeostasis. ^{[4] [5]} Both senescence and the SASP are sensitive to cellular and organismal metabolic states, which in turn can drive phenotypes associated with metabolic dysfunction. ^[2] Mitochondrial dysfunction plays an important role not only in the senescence growth arrest but also in the development of the SASP and in resistance to cell death. ^[6]

The SASP fuels chronic inflammation and contributes to cancer and age-related tissue dysfunction, and is now considered an underlying driver of age-related inflammatory disease. ^{[7] [8]} Factors secreted as part of the SASP promote chronic inflammation, and this vicious cycle of inflammation and senescence contributes to organ damage and aging-related diseases. ^[4] The SASP has context-dependent effects, associated with both tumour-suppressive senescence surveillance and tumour-promoting suppression of anti-tumour immunity. ^[3]

SASP-centered approaches are emerging as alternatives or complements to senolytics for targeting senescence-associated diseases. ^[9] Drugs that suppress the SASP are termed senomorphics, in contrast to senolytics that selectively kill senescent cells. ^{[3] [1]} The SASP is being explored both as a biomarker of senescence and as a target for senomorphic interventions to treat cancer and other age-related conditions. ^[1]