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bioRxiv · 10.1101/2025.01.07.631588

Mitigating Proinflammatory SASP and DAMP with Urolithin A: A Novel Senomorphic Strategy

Barkovskaya, A.·Brauning, A.·Chamoli, M.·Rane, A.·Andersen, J. K.·Sharma, A.
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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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Barkovskaya, A., Brauning, A., Chamoli, M., Rane, A., Andersen, J. K., Sharma, A.. 2025-01-08. Mitigating Proinflammatory SASP and DAMP with Urolithin A: A Novel Senomorphic Strategy. https://doi.org/10.1101/2025.01.07.631588

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