Senescence— Before Birth

Cellular senescence— defined as a process of stable cell-cycle arrest—was first identified as a biological state that marked the end of a cell’s replicative life (Hayflick, 1965). In the investigations that followed, senescence was established as a component of disease states {e.g. DNA damage} (Kuilman et al., 2010), and was correlated with aging-associated disorders (Keyes et al., 2005; Baker et al., 2011). It was also shown that cells attain oncogene-induced senescence {OIS} when triggered by intense oncogene signaling {e.g. ras} (Serrano et al., 1997). Senescent cells also participate in extensive signaling to the immune system for their own clearance due to their distinct senescence-associated secretory phenotype (Kuilman et al., 2010). Overall, senescence was widely considered a component of cellular response to disease states.