Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.

Seyed Soheil Saeedi Saravi, Benoit Pugin, Florentin Constancias, Khatereh Shabanian, Marianne Spalinger, Aurélien Thomas, Sylvain Le Gludic, Taraneh Shabanian, Gergely Karsai, Manuel Colucci, Cristina Menni, Ilias Attaye, Xinyuan Zhang, Meret Sarah Allemann, Pratintip Lee, Alessia Visconti, Mario Falchi, Andrea Alimonti, Frank Ruschitzka, Francesco Paneni, Jürg H Beer

Center for Translational and Experimental Cardiology, Department of Cardiology, University Hospital Zurich, University of Zurich, Schlieren, Switzerland. [email protected]. · pubmed

Paper

Abstract

Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H

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Research summary

The paper claims that the gut bacterial metabolite phenylacetic acid induces endothelial cell senescence, contributing to cardiovascular aging. This research addresses a potential mechanism underlying aging processes, specifically endothelial cell senescence, which is relevant to understanding and potentially mitigating age-related decline.

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