SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells
Summary: 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719310976 |
| _version_ | 1818359602594447360 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Christopher D. Wiley |
| collection | DOAJ |
| description | Summary: 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. : Wiley et al. identify new proteins secreted by senescent cells using unbiased proteomics, including factors involved in hemostasis. Secretions of senescent cells increase human platelet activation, while eliminating senescent cells prevents increases in platelet counts and activation in mice treated with chemotherapy. Senescent cells may thus underlie clotting predisposition. Keywords: cellular senescence, aging, homeostasis, coagulation, clotting, thrombosis, chemotherapy, SASP, secretion, proteomics |
| first_indexed | 2024-12-13T20:47:30Z |
| format | Article |
| id | doaj.art-18d57d9f49ba45cebd45a0fa32ce2405 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T20:47:30Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-18d57d9f49ba45cebd45a0fa32ce24052022-12-21T23:31:57ZengElsevierCell Reports2211-12472019-09-01281333293337.e5SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent CellsChristopher D. Wiley0Su Liu1Chandani Limbad2Anna M. Zawadzka3Jennifer Beck4Marco Demaria5Robert Artwood6Fatouma Alimirah7Jose-Alberto Lopez-Dominguez8Chisaka Kuehnemann9Steven R. Danielson10Natan Basisty11Herbert G. Kasler12Tal Ronnen Oron13Pierre-Yves Desprez14Sean D. Mooney15Bradford W. Gibson16Birgit Schilling17Judith Campisi18Pankaj Kapahi19Buck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USAEuropean Institute for the Biology of Aging, University of Groningen, Groningen, the NetherlandsBuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USA; California Pacific Medical Center, Research Institute, San Francisco, CA 94107, USADepartment of Biomedical Informatics & Medical Education, University of Washington, Seattle, WA 98195, USADiscovery Attribute Sciences, Amgen Inc., South San Francisco, CA 94080, USABuck Institute for Research on Aging, Novato, CA 94945, USABuck Institute for Research on Aging, Novato, CA 94945, USA; Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Corresponding authorBuck Institute for Research on Aging, Novato, CA 94945, USA; Corresponding authorSummary: 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. : Wiley et al. identify new proteins secreted by senescent cells using unbiased proteomics, including factors involved in hemostasis. Secretions of senescent cells increase human platelet activation, while eliminating senescent cells prevents increases in platelet counts and activation in mice treated with chemotherapy. Senescent cells may thus underlie clotting predisposition. Keywords: cellular senescence, aging, homeostasis, coagulation, clotting, thrombosis, chemotherapy, SASP, secretion, proteomicshttp://www.sciencedirect.com/science/article/pii/S2211124719310976 |
| spellingShingle | 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 SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells Cell Reports |
| title | SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells |
| title_full | SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells |
| title_fullStr | SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells |
| title_full_unstemmed | SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells |
| title_short | SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells |
| title_sort | silac analysis reveals increased secretion of hemostasis related factors by senescent cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719310976 |
| work_keys_str_mv | AT christopherdwiley silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT suliu silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT chandanilimbad silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT annamzawadzka silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT jenniferbeck silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT marcodemaria silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT robertartwood silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT fatoumaalimirah silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT josealbertolopezdominguez silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT chisakakuehnemann silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT stevenrdanielson silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT natanbasisty silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT herbertgkasler silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT talronnenoron silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT pierreyvesdesprez silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT seandmooney silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT bradfordwgibson silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT birgitschilling silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT judithcampisi silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells AT pankajkapahi silacanalysisrevealsincreasedsecretionofhemostasisrelatedfactorsbysenescentcells |