Hsp90 inhibitors as senolytic drugs to extend healthy aging

Abstract

Aging is characterized by progressive decay of biological systems and although it is not considered a disease, it is one of the main risk factors for chronic diseases and many types of cancers. The accumulation of senescent cells in various tissues is thought to be a major factor contributing to aging and age-related diseases. Removal of senescent cells during aging by either genetic or therapeutic methods have led to an improvement of several age related disease in mice. In this preview, we highlight the significance of developing senotherapeutic approaches to specifically kill senescent cells (senolytics) or suppress the senescence-associated secretory phenotype (SASP) that drives sterile inflammation (senomorphics) associated with aging to extend healthspan and potentially lifespan. Also, we provide an overview of the senotherapeutic drugs identified to date. In particular, we discuss and expand upon the recent identification of inhibitors of the HSP90 co-chaperone as a new class of senolytics.