Identification of HSP90 inhibitors as a novel class of senolytics

Abstract Aging is the main risk factor for many chronic degenerative diseases and cancer. Increased senescent cell burden in various tissues is a major contributor to aging and age-related diseases. Recently, a new class of drugs termed senolytics were demonstrated to extending healthspan, reducing frailty and improving stem cell function in multiple murine models of aging. To identify novel and more optimal senotherapeutic drugs and combinations, we established a senescence associated β-galactosidase assay as a screening platform to rapidly identify drugs that specifically affect senescent cells. We used primary Ercc1 −/− murine embryonic fibroblasts with reduced DNA repair capacity, which senesce rapidly if…

• AF
  American Federation for Aging Research
• NI
  National Institutes of Health

  Awards: AG13925, AG043376, DK50456