Senescence Inducers and Senolytics – Pathways and Drugs Targeting Cellular Senescence

Physiologic aging and insults from the environment lead to DNA damage. In response, cells in any organ will undergo senescence-induced growth arrest to prevent damaged cells from further propagation. This review focuses on senescence pharmacology. First, we describe senescence induction mechanisms and a unique feature of senescent cells, the SASP (senescence-associated secretory phenotype). Signaling pathways that control and respond to the SASP provide the framework for a better understanding of senescence pharmacology. We describe how several commonly used drugs can induce cellular senescence and how that impacts their efficacy and produces unexpected effects. Thereafter, we discuss the potential and challenges of senolytic drugs that eliminate senescent cells, and we describe targeting of components of the SASP as well as pathways that control expression of genes contributing to the SASP. Lastly, we discuss studies that have exemplified the significant impact of senescence-targeted therapy in various disease states.