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New Perspectives on Gastric Inflammaging: Integrating Multi-Omics Mechanisms and Gerotherapeutic Strategies in Chronic Gastritis

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

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Opinion: We crunched the numbers on drug discovery in the U.S. vs. China. The results were alarming

This essay is part of a First Opinion series on the future of the National Institutes of Health and American science.

Around the world, nations with robust research and development infrastructure race to create therapeutics that meet the needs of their residents. Simply put, they dictate research priorities based on need. During the Covid pandemic, the United States was one of the first countries to gain access to vaccines to protect its citizens.

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Generative AI Mental Health Chatbots as Therapeutic Tools: Systematic Review and Meta-Analysis of Their Role in Reducing Mental Health Issues

Background: To date, there is no comprehensive paper that systematically synthesizes the effect of generative AI chatbot’s impact on mental health. Can generative AI chatbots help reduce our psychological distress? Objective: To comprehensively assess existing evidence, a systematic review and meta-analysis is essential to evaluate the overall effectiveness, identify gaps, and guide future research in this evolving field. This paper aims to: 1) synthesize current evidence on generative AI chatbot interventions targeting mental health issues, 2) quantify the effectiveness of these interventions via a meta-analysis of randomized controlled trials (RCTs), and examine key moderators of intervention effectiveness. Methods: This systematic review included 26 studies for narrative synthesis, out of which 12 randomized controlled trials were included in the meta-analysis. Results: The systematic synthesis revealed that 1) generative AI-chatbot interventions mostly took place in non-WEIRD countries (Western, Educated, Industrialized, Rich, and Democratic) and 2) there is a lack of studies focusing on young children and older adults. The meta-analysis showed a statistically significant effect (ES = 0.36, p = .039), which means that generative AI chatbots are, on average, effective in reducing negative mental health issues. Among moderators, we found statistically significant and higher effect sizes among interventions that have an active control group, conducted in WEIRD countries, recruited non-clinical populations, older age, majority female, non-personalized, with human assistance, and social-oriented. Conclusions: In conclusion, this comprehensive review has highlighted the potential of generative AI chatbots in addressing anxiety, depression, negative mood, and stress. The findings indicate that generative AI interventions are particularly beneficial in WEIRD countries, among non-clinical populations, older adults, and females. Human-assisted and social-oriented programs, as opposed to fully autonomous or task-oriented ones, demonstrate greater effectiveness. Meanwhile, non-personalized chatbots appear to yield more effective outcomes than personalized systems.
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