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

[EN]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 prote...

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Detalles Bibliográficos
Autores: Wiley, Christopher D, Liu, Su, Limbad, Chandani, Zawadzka, Anna M, Beck, Jennifer, Demaria, Marco, Artwood, Robert, Alimirah, Fatouma, López Domínguez, José Alberto, Kuehnemann, Chisaka, Danielson, Steven R, Basisty, Natan, Kasler, Herbert G, Oron, Tal Ronnen, Desprez, Pierre-Yves, Mooney, Sean D, Gibson, Bradford W, Schilling, Birgit, Campisi, Judith, Kapahi, Pankaj
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166751
Acceso en línea:http://hdl.handle.net/10366/166751
Access Level:acceso abierto
Palabra clave:Cellular senescence
Aging
SASP
Hemostasis
Humans
2302 Bioquímica
2415 Biología Molecular
hemostasia
humanos
Descripción
Sumario:[EN]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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