Longevity & AgingHow Aging Disrupts Liver Ammonia Processing and Accelerates Systemic Decline
The liver is responsible for clearing ammonia — a toxic byproduct of protein metabolism — through the urea cycle and glutamine synthesis. This review reveals that aging progressively impairs these pathways through mitochondrial dysfunction, epigenetic changes, and disrupted metabolic zonation. As ammonia accumulates, it doesn't just reflect failing liver health; it actively drives cellular senescence, protein homeostasis defects, inflammation, and fibrosis. The consequences extend beyond the liver, affecting the brain, muscles, and gut microbiome through interconnected physiological axes. Crucially, the review positions ammonia not merely as metabolic waste but as a bioactive stress signal that amplifies aging processes. Therapeutic strategies discussed include ammonia-lowering drugs, senolytic agents, and microbiome-targeting interventions, offering a roadmap for addressing this underappreciated aging mechanism.
