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

Front Immunol. 2025 Sep 12;16:1638445. doi: 10.3389/fimmu.2025.1638445. eCollection 2025.

ABSTRACT

BACKGROUND: Air pollution may crosstalk with immune system to promote hepatocellular carcinoma (HCC) development, but its precise mechanisms and prognostic significance remain unclear.

OBJECTIVE: This study aims to construct a prognostic signature for HCC based on air pollutant-related immune genes (APIGs).

METHODS: We obtained mRNA-seq and scRNA of HCC from GEO, TCGA and ICGC. AP-related target genes were retrieved from several online databases. APIGs were obtained using WGCNA, differential gene expression analysis and immune infiltration analysis. Molecular subtypes were conducted based on APIG expression to characterize immune features. A total of 101 combinations of 10 machine learning algorithms were used to construct an APIG-based prognostic signature (APIGPS). Furthermore, we performed qRT-PCR, survival analyses, functional enrichment, immune infiltration and single-cell analyses. Subsequently, LASSO, RF, and RFE-SVM were employed to identify diagnostic genes, followed by pan-cancer analysis.

RESULTS: We identified 19 APIGs. HCC samples were divided into 3 subtypes, with C1 exhibiting a pro-tumor immune microenvironment and poorer prognosis. APIGPS constructed by 7 APIGs (CDC25C, MELK, ATG4B, SLC2A1, CDC25B, APEX1, GLS), demonstrated robust predictive ability independent of clinical features. The biological pathway differences between APIGPS-based high- and low-risk groups involved immune responses and cell proliferation and migration. APIGPS genes had stable binding to 7 APs and were mainly expressed in macrophages, with HRG exhibiting higher macrophage abundance. CDC25C was identified as the hub gene after intersecting diagnostic genes and APIGPS genes. CDC25C was associated with survival of 10 cancers, MSI in 10 cancers, TMB in 21 cancers, and immune cell abundance in 13 cancers.

CONCLUSIONS: We identified key APIGs and constructed a robust APIG-based prognostic signature for HCC. CDC25C was a key target through which APs impact HCC and multiple other cancers.

PMID:41019083 | PMC:PMC12463942 | DOI:10.3389/fimmu.2025.1638445

Cell. 2025 Aug 22:S0092-8674(25)00922-5. doi: 10.1016/j.cell.2025.08.008. Online ahead of print.

ABSTRACT

Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage. We demonstrated the robust performance of Stereo-seq V2 on clinical FFPE samples using triple-negative breast cancer (TNBC) sections and identified tumor-specific alternative splicing events. In a Mycobacterium tuberculosis (Mtb)-infected mouse model, we monitored gene expression dynamics of host and pathogen transcriptomes simultaneously by utilizing Stereo-seq V2. We also assembled immune repertoires and identified Mtb-specific BCR clones, which could also be observed in human tuberculous lung samples. These results highlight Stereo-seq V2's potential in biomedical research and personalized medicine.

PMID:40882628 | DOI:10.1016/j.cell.2025.08.008