Senolytics: Targeting Senescent Cells for Age-Associated Diseases

Purpose of Review Evidence suggests that senescent cells drive aging and age-related diseases, with interventions that clear them improving various conditions in preclinical models. Efforts to discover senolytics, drugs that can specifically kill senescent cells, are ongoing, guided by studies into their biology and several in vivo models. This review describes recently discovered senolytics and the pathways they target. Recent Findings Drugs targeting the BCL-2 family proteins, p53 activators, HSP90 inhibitors, cardiac glycosides, and fibrates along with several flavonoids are senolytic in vitro and in vivo. Methods for specifically delivering death to senescent cells to decrease non-specific off-target effects take advantage of their characteristic elevated level of p16 and increased β-galactosidase activity. Summary Effects of senolytics on age-related diseases in pre-clinical models have been so striking that several proof-of-concept and safety phase I human trials have begun. The search continues for additional senolytics that can target more types of senescent cells with the least side effects.