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.
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Research summary
Urolithin A lowers the expression and release of pro-inflammatory SASP and DAMP factors, contributing to a senomorphic strategy against aging. The paper is relevant as it addresses the underlying mechanisms of senescence and inflammation, which are critical factors in the aging process and age-related diseases.
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