Aging Dis. 2025 Dec 15. doi: 10.14336/AD.2025.1444. Online ahead of print.

ABSTRACT

Chronic gastritis (CG) is a highly prevalent, age-associated inflammatory disorder of gastric mucosa and a key precursor of gastric cancer in older adults. Beyond Helicobacter pylori infection and environmental insults, accumulating evidence indicates that chronic, low-grade inflammation coupled with aging biology, "gastric inflammaging", plays a central role in driving mucosal degeneration, atrophy, and malignant transformation. Here, we synthesize current mechanistic and multi-omics evidence to conceptualize CG as a tractable model of organ-specific inflammaging. We first summarize how hallmarks of aging-including cellular senescence and the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, impaired autophagy, immune exhaustion, and microbiome dysbiosis-converge to create a self-perpetuating inflammatory microenvironment in the stomach. We then review emerging single-cell and spatial multi-omics studies that delineate senescence-inflammation niches and reveal how these molecular neighborhoods relate to disease stage and cancer risk. Finally, we discuss therapeutic implications, highlighting geroscience-guided interventions such as senolytics/senomorphics, inflammasome and cGAS-STING pathway modulators, microbiota- and metabolite-targeted strategies, lifestyle interventions, and natural products, and propose a precision framework linking inflammaging biomarkers to patient stratification and clinical endpoints. Reframing CG as a gastric inflammaging model may provide a prototype for organ-specific healthy aging strategies and near-term gerotherapeutic trials aimed at extending healthspan.

PMID:41400573 | DOI:10.14336/AD.2025.1444