puc-header

SILAC Analysis Reveals a Role for the Senescence-Associated Secretory Phenotype in Hemostasis

37 Pages Posted: 12 Apr 2018 Publication Status: Published

See all articles by Christopher Wiley

Christopher Wiley

Buck Institute for Research on Aging

Su Liu

Buck Institute for Research on Aging

Chandani Limbad

Buck Institute for Research on Aging

Anna Zawadzka

Buck Institute for Research on Aging

Jennifer Beck

Buck Institute for Research on Aging

Marco Demaria

Buck Institute for Research on Aging

Robert Artwood

Buck Institute for Research on Aging

Fatouma Alimirah

Buck Institute for Research on Aging

Steven R. Danielson

Buck Institute for Research on Aging

Tal Ronnen Oron

Buck Institute for Research on Aging

Pierre-Yves Desprez

Buck Institute for Research on Aging

Sean Mooney

Buck Institute for Research on Aging

Bradford W. Gibson

Buck Institute for Research on Aging

Birgit Schilling

Buck Institute for Research on Aging

Judith Campisi

Buck Institute for Research on Aging; University of California, Berkeley - Lawrence Berkeley National Laboratory (Berkeley Lab)

Pankaj Kapahi

Buck Institute for Research on Aging

More...

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 in cell culture (SILAC), we identify 343 SASP proteins that senescent human fibroblasts secrete at 2-fold or higher levels compared to quiescent cell counterparts. Bioinformatic analysis revealed that 44 of these SASP factors are involved in hemostasis, a process not previously linked with cellular senescence. We validate the expression of some of these SASP factors in cell culture and in vivo. Mice treated with the chemotherapeutic agent doxorubicin, which induces widespread cellular senescence in vivo, show increased blood clotting. Conversely, use of a transgene that permits the selective removal of senescent cells shows that senescent cell clearance attenuates the increased clotting shown by doxorubicin-treated mice. Together, our study characterizes a SASP profile using SILAC, unveiling a novel function for cellular senescence in hemostasis.

Keywords: cellular senescence; SASP; SILAC; chemotherapy; hemostasis; aging

Suggested Citation

Wiley, Christopher and Liu, Su and Limbad, Chandani and Zawadzka, Anna and Beck, Jennifer and Demaria, Marco and Artwood, Robert and Alimirah, Fatouma and Danielson, Steven R. and Oron, Tal Ronnen and Desprez, Pierre-Yves and Mooney, Sean and Gibson, Bradford W. and Schilling, Birgit and Campisi, Judith and Kapahi, Pankaj, SILAC Analysis Reveals a Role for the Senescence-Associated Secretory Phenotype in Hemostasis (2018). Available at SSRN: https://ssrn.com/abstract=3155773 or http://dx.doi.org/10.2139/ssrn.3155773
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Christopher Wiley

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Su Liu

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Chandani Limbad

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Anna Zawadzka

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Jennifer Beck

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Marco Demaria

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Robert Artwood

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Fatouma Alimirah

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Steven R. Danielson

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Tal Ronnen Oron

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Pierre-Yves Desprez

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Sean Mooney

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Bradford W. Gibson

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Birgit Schilling

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Judith Campisi

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

University of California, Berkeley - Lawrence Berkeley National Laboratory (Berkeley Lab)

1 Cyclotron Road
Berkeley, CA 94720
United States

Pankaj Kapahi (Contact Author)

Buck Institute for Research on Aging ( email )

8001 Redwood Boulevard
Novato, CA 94945
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
503
Downloads
14
PlumX Metrics