Salvianolic acids are natural senolytics and increase lifespan in old age

Cellular senescence plays a critical role in chronological aging and has been implicated in the onset and progression of multiple age-related disorders. Targeting senescent cells represents a promising strategy to reduce pathological burden and improve healthspan. Here we report the senotherapeutic properties of salvianolic acid (SA) family members, specifically A (SAA), B (SAB) and E (SAE). From a natural medicinal agent library, we identified selective cytotoxicity of these SA compounds against diverse types of senescent cells and originating cell lineages. Mechanistically, SAA, SAB and SAE enhance ROS production and target glutathione S-transferase Pi1 (GSTP1), a redox homeostasis modulator, inducing both apoptosis and ferroptosis in senescent cells. Incorporation of SAs into chemotherapeutic regimens enhanced anticancer efficacy and prolonged post-treatment survival. Intermittent SA administration improved physical function and increased healthspan and lifespan in aged mice. Our study establishes SAs as an emerging class of natural senolytics (phenolic acids) with the capacity to delay fundamental aging processes and alleviate multiple pathologies in advanced life.