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

摘要

Cellular senescence irreversibly arrests cell proliferation,accompanied by a multi-component senescence-associatedsecretory phenotype (SASP) thatparticipates in several age-related diseases. Usingstable isotope labeling with amino acids (SILACs)and cultured cells, we identify 343 SASP proteinsthat senescent human fibroblasts secrete at 2-foldor higher levels compared with quiescent cell counterparts.Bioinformatic analysis reveals that 44 ofthese proteins participate in hemostasis, a processnot previously linked with cellular senescence. Wevalidated the expression of some of these SASP factorsin cultured cells and in vivo. Mice treated with thechemotherapeutic agent doxorubicin, which induceswidespread cellular senescence in vivo, showincreased blood clotting. Conversely, selectiveremoval of senescent cells using transgenic p16-3MR mice showed that clearing senescent cellsattenuates the increased clotting caused by doxorubicin.Our study provides an in-depth, unbiased analysisof the SASP and unveils a function for cellularsenescence in hemostasis.