Cellular Senescence as a Program of the Innate Immune System

We describe here an essential innate immune signaling pathway in oncogene-induced senescence (OIS) established between TLR2 and acute-phase serum amyloid A1 and serum amyloid A2 (A-SAAs) that initiates the senescence-associated secretory phenotype (SASP) and reinforce cellular senescence in vitro and in vivo. We also identify new important SASP components, A-SAAs, which are the senescence-associated damage-associated molecular patterns (DAMPs) sensed by TLR2 after oncogenic stress. Therefore, we are reporting that innate immune sensing is critical in senescence. We propose that cellular senescence shares mechanistic features with the activation of innate immune cells and could be considered a program of the innate immune response by which somatic cells switch their regular role to acquire an immune function under certain conditions of stress and danger, for instance, upon oncogene activation. Besides revealing a role for TLR2 in SASP induction and cell cycle regulation, we identified the DAMP that activates TLR2 in OIS. Acute-phase proteins SAA1 and SAA2 act to prime the TLR2-mediated inflammasome, and in turn, their full induction depends on TLR2 function. Hence, they establish a foundational feedback loop that controls the SASP. A-SAAs are systemically produced in the liver and released into the bloodstream during an acute inflammatory response. Our identification of these molecules as mediators of senescence suggests that systemic elevation of A-SAAs might have an i...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs