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

Wiley, Christopher D.; Liu, Su; Limbad, Chandani; Zawadzka, Anna M.; Beck, Jennifer; Demaria, Marco; Artwood, Robert; Alimirah, Fatouma; Lopez-Dominguez, Jose-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

doi:10.1016/j.celrep.2019.08.049

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

Journal Article · Tue Sep 24 00:00:00 EDT 2019 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2019.08.049· OSTI ID:1591812

Wiley, Christopher D. ^[1]; Liu, Su ^[1]; Limbad, Chandani ^[1]; Zawadzka, Anna M. ^[1]; Beck, Jennifer ^[1]; Demaria, Marco ^[2]; Artwood, Robert ^[1]; Alimirah, Fatouma ^[1]; Lopez-Dominguez, Jose-Alberto ^[1]; Kuehnemann, Chisaka ^[1]; Danielson, Steven R. ^[1]; Basisty, Natan ^[1]; Kasler, Herbert G. ^[1]; Oron, Tal Ronnen ^[1]; Desprez, Pierre-Yves ^[3]; Mooney, Sean D. ^[4]; Gibson, Bradford W. ^[5]; Schilling, Birgit ^[1]; Campisi, Judith ^[6]; Kapahi, Pankaj ^[1]

Buck Inst. for Research on Aging, Novato, CA (United States)
Univ. of Groningen (Netherlands)
Buck Inst. for Research on Aging, Novato, CA (United States); California Pacific Medical Center, San Francisco, CA (United States)
Univ. of Washington, Seattle, WA (United States)
Amgen Inc., South San Francisco, CA (United States)
Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1591812

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 13 Vol. 28; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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