MicroRNA and senescence: the senectome, integration and distributed control.

Cellular senescence has attracted renewed interest in recent years in light of the realization that cancer cells are susceptible to senescence-like responses to stress including exposure to chemotherapeutic agents. Therefore, senescence is viewed as a potentially important target in cancer therapy. However, translation of senescence therapeutics will rely on identifying appropriate marker panels for assessing senescence responses in vivo. Although some core pathways governing senescence induction have been clearly identified, the full set of gene targets involved in its establishment and maintenance are not defined and their complex interactions are poorly understood. This view is reinforced by recently discovered roles of microRNA (miRNA) in senescence regulation and induction. Senescence involves coordination of diverse cellular processes ranging from telomere homeostasis and DNA damage to chromatin modifications, inflammatory signaling, and metabolic and cytoskeletal changes. Thus, from a target discovery perspective a "senectome" view is appropriate. miRNAs are well placed to act as distributed senectome control elements, fine-tuning regulation of multiple processes. Here, we examine the complex interactions among several of these subprocesses and subsequently consider senescence-associated miRNAs (SA-miRNAs) as distributed controllers of senectome regulation. Finally, we examine their potential as clinical biomarkers to accelerate development of senescence therapeutics.