Mitigating Proinflammatory 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, on the downregulation of cytosolic DNA release and subsequent decrease in cGAS-STING signaling.
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Research summary
The paper addresses a novel senomorphic strategy to mitigate pro-inflammatory factors associated with senescent cells, which is directly related to the root causes of aging and age-related diseases. While the findings are solid and contribute to the understanding of senescence and inflammation in aging, the impact appears to be limited in scope and may not significantly advance the field compared to more groundbreaking studies.
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