Senescent Cells Implicated in Age-Related Changes in Blood Clotting

In this study, researchers validated the expression of some of the specific factors in cultured cells and in mice, which were treated with doxorubicin, a widely-used chemotherapy drug which induces widespread senescence. Those mice showed increased blood clotting, similar to what happens in humans who undergo chemotherapy. "Conversely, when we selectively removed senescent cells in specially bred transgenic mice, the increased clotting caused by doxorubicin went away." SILAC Analysis Reveals Increased Secretion of Hemostasis-Related Factors by Senescent Cells 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 attenua...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs