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

Barkovskaya, Anna; Brauning, Ashley; Thambala, Aditi; Bhardwaj, Kriti; Chamoli, Manish; Rane, Anand; Andersen, Julie K; Sharma, Amit · Aging Cell · 2025

basic_science · Level V

Where this comes from

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.

Medical subject headings