Mitigating Pro‐Inflammatory SASP and DAMP With Urolithin A: A Novel Senomorphic Strategy

ABSTRACT Senescent cells are known to contribute to aging and age‐related diseases. One key way they influence aging is by secreting senescence‐associated secretory phenotype (SASP) factors along with several damage‐associated molecular pattern (DAMP) molecules. Consequently, inhibiting SASP and DAMP signaling (senomorphics) has emerged as a therapeutic strategy. Urolithin A (UA), a gut‐derived metabolite produced from ellagitannins and ellagic acid found in berries, nuts, and pomegranates, has demonstrated potent anti‐inflammatory properties and protective effects against aging and age‐related conditions in experimental models. Here we demonstrate that UA lowers the expression and release of pro‐inflammatory SASP and DAMP factors, at least in part, by downregulating cytosolic DNA release and subsequent decrease in cGAS‐STING signaling.