Targeting the senescence-associated secretory phenotype - Kevin Perrott
Loss of normal tissue homeostasis with age is accompanied by a low but detectable rise in pro-inflammatory factors in the absence of detectable infection. The source of this "sterile" inflammation is unknown however senescent cells have been identified as a possible origin with the identification of the 'senescence-associated secretory phenotype' (SASP) exhibited by many proliferation-capable cell-types in response to genomic damage. Recent studies have shown that removal senescent cells in a rapidly aging mouse model increases healthspan identifying senescent cells and their secretory phenotype as potentially causal in the loss of tissue homeostasis and degenerative processes. Understanding the SASP and discovering ways of reducing its proinflammatory nature could be beneficial in preserving or restoring function to aging tissues. To examine this potential the Campisi lab has screened 1400 FDA approved compounds to identify those able to lower the SASP. The focus of this work is validating and selecting some of the candidate compounds for this ability and determining their mechanism of action. One candidate selected for further characterization and study is the flavonoid Apigenin. Its effects on the SASP of senescent cells will be discussed revealing some novel insights into the secretory profile of senescent cells and how it may contribute to aging phenotypes.