Longevity & AgingGut Bacteria Metabolite PAA Drives Vascular Aging by Triggering Endothelial Senescence
Researchers discovered that phenylacetic acid (PAA), a metabolite produced by gut bacteria from phenylalanine, increases significantly with age in both humans and mice. Elevated PAA—linked to the bacterium Clostridium sp. ASF356—induces endothelial cell senescence by triggering mitochondrial hydrogen peroxide production and amplifying the senescence-associated secretory phenotype (SASP). Meanwhile, fecal acetate levels decline with age, removing a natural brake on senescence that operates via Sirt1-dependent pathways. Supplementing with sodium acetate countered PAA-induced senescence and restored angiogenic function, suggesting a microbiome-based therapeutic strategy for reducing vascular aging and associated cardiovascular disease risk.
