The study explores the potential of senolytics, drugs that selectively eliminate senescent cells, to improve healthspan and reduce age-related chronic diseases. By transcript analysis, the researchers identified increased expression of pro-survival networks in senescent cells, which are resistant to apoptosis. Using siRNA to silence key nodes of this network, including ephrins, PI3Kα, p21, BCL-xL, and plasminogen-activated inhibitor-2, they found that these drugs selectively killed senescent cells without affecting proliferating or quiescent cells. Dasatinib and quercetin were effective in eliminating senescent cells in vitro and in vivo, reducing senescent cell burden in aged mice and improving cardiac function and exercise capacity. Periodic administration of these drugs extended healthspan in progeroid mice, delaying age-related symptoms and pathology. The findings suggest that senolytics could be a promising therapeutic approach to alleviate symptoms of frailty and extend healthspan.The study explores the potential of senolytics, drugs that selectively eliminate senescent cells, to improve healthspan and reduce age-related chronic diseases. By transcript analysis, the researchers identified increased expression of pro-survival networks in senescent cells, which are resistant to apoptosis. Using siRNA to silence key nodes of this network, including ephrins, PI3Kα, p21, BCL-xL, and plasminogen-activated inhibitor-2, they found that these drugs selectively killed senescent cells without affecting proliferating or quiescent cells. Dasatinib and quercetin were effective in eliminating senescent cells in vitro and in vivo, reducing senescent cell burden in aged mice and improving cardiac function and exercise capacity. Periodic administration of these drugs extended healthspan in progeroid mice, delaying age-related symptoms and pathology. The findings suggest that senolytics could be a promising therapeutic approach to alleviate symptoms of frailty and extend healthspan.