Senescence-associated secretory phenotype

Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases.[1][2] SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors.[3][4] Soluble urokinase plasminogen activator surface receptor is part of SASP, and has been used to identify senescent cells for senolytic therapy.[5] Initially, SASP is immunosuppressive (characterized by TGF-β1 and TGF-β3) and profibrotic, but progresses to become proinflammatory (characterized by IL-1β, IL-6 and IL-8) and fibrolytic.[6][7] SASP is the primary cause of the detrimental effects of senescent cells.[4]

SASP is heterogenous, with the exact composition dependent upon the senescent-cell inducer and the cell type.[4][8] Interleukin 12 (IL-12) and Interleukin 10 (IL-10) are increased more than 200-fold in replicative senescence in contrast to stress-induced senescence or proteosome-inhibited senescence where the increases are about 30-fold or less.[9] Tumor necrosis factor (TNF) is increased 32-fold in stress-induced senescence, 8-fold in replicative senescence, and only slightly in proteosome-inhibited senescence.[9] Interleukin 6 (IL-6) and interleukin 8 (IL-8) are the most conserved and robust features of SASP.[10] But some SASP components are anti-inflammatory.[11]

Senescence and SASP can also occur in post-mitotic cells, notably neurons.[12] The SASP in senescent neurons can vary according to cell type, the initiator of senescence, and the stage of senescence. [12]

An online SASP Atlas serves as a guide to the various types of SASP.[8]

SASP is one of the three main features of senescent cells, the other two features being arrested cell growth, and resistance to apoptosis.[13] SASP factors can include the anti-apoptotic protein Bcl-xL,[14] but growth arrest and SASP production are independently regulated.[15] Although SASP from senescent cells can kill neighboring normal cells, the apoptosis-resistance of senescent cells protects those cells from SASP.[16]

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