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SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells.

Cell reports (2019-09-26)
Christopher D Wiley, Su Liu, Chandani Limbad, Anna M Zawadzka, Jennifer Beck, Marco Demaria, Robert Artwood, Fatouma Alimirah, Jose-Alberto Lopez-Dominguez, Chisaka Kuehnemann, Steven R Danielson, Natan Basisty, Herbert G Kasler, Tal Ronnen Oron, Pierre-Yves Desprez, Sean D Mooney, Bradford W Gibson, Birgit Schilling, Judith Campisi, Pankaj Kapahi
ABSTRACT

Cellular senescence irreversibly arrests cell proliferation, accompanied by a multi-component senescence-associated secretory phenotype (SASP) that participates in several age-related diseases. Using stable isotope labeling with amino acids (SILACs) and cultured cells, we identify 343 SASP proteins that senescent human fibroblasts secrete at 2-fold or higher levels compared with quiescent cell counterparts. Bioinformatic analysis reveals that 44 of these proteins participate in hemostasis, a process not previously linked with cellular senescence. We validated the expression of some of these SASP factors in cultured cells and in vivo. Mice treated with the chemotherapeutic agent doxorubicin, which induces widespread cellular senescence in vivo, show increased blood clotting. Conversely, selective removal of senescent cells using transgenic p16-3MR mice showed that clearing senescent cells attenuates the increased clotting caused by doxorubicin. Our study provides an in-depth, unbiased analysis of the SASP and unveils a function for cellular senescence in hemostasis.

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