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Multi-omics analysis reveals diagnostic and therapeutic biomarkers for aging phenotypes in ulcerative colitis

by Lei Guo, Jun Ge, Li Cheng, Xinyi Zhang, Zhengzheng Wu, Meili Liu, Hanmei Jiang, Wei Gong, Yi Liu

Background

The incidence of ulcerative colitis (UC) remains high, with an increasing prevalence among elderly patients. Cellular senescence has been widely recognized as a contributor to UC susceptibility; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to identify senescence-associated biomarkers in UC to provide new insight for diagnosis and treatment.

Methods

By integrating transcriptomic data from UC patients with established aging-related databases, we identified aging-associated differentially expressed genes (DEGs). Using weighted gene co-expression network analysis (WGCNA) and Cytoscape, we pinpointed the core genes involved. A diagnostic model for UC was then developed based on these core genes, and their expression patterns were characterized at single-cell resolution. The roles of these genes were ultimately validated through in vitro and animal experiments.

Results

We identified 24 aging-related DEGs in UC, which were primarily implicated in inflammatory responses and cytokine-receptor interactions. Further analyses pinpointed three core genes (CXCL1, MMP9, and STAT1) that were predominantly expressed in macrophages. A diagnostic model constructed using these genes exhibited robust predictive performance. Experimental validation confirmed that the expression levels of all three core genes were significantly upregulated in both a UC mouse model and in macrophages compared to controls. Additionally, pathway analyses revealed elevated levels of CXCL12 and VEGFA in the enriched pathways.

Discussion

Our findings underscore the pivotal roles of CXCL1, MMP9, and STAT1 in UC-associated cellular senescence. The analysis positions these molecules as promising macrophage-mediated diagnostic biomarkers and therapeutic targets. Collectively, this work provides novel insights into UC pathogenesis and lays a foundation for developing precision medicine strategies that target senescence pathways.

The independent and combined effects of physical activity and depressive symptoms on frailty in community‐dwelling older adults: A cross‐sectional study

Abstract

Aims

To investigate the independent and combined effects of physical activity (PA) and depressive symptoms on the risk of frailty in community-dwelling older adults.

Background

Older adults face a high risk of frailty which is commonly used to predict adverse health outcomes in older patients. Engaging in PA and without depressive symptoms are crucial factors to prevent frailty. It is essential to investigate the independent and combined effects of these two variables on the risk of frailty.

Methods

We included 3392 community-dwelling older adults. The FRAIL Scale was used to assess older adults' frail status (robust, prefrail and frail). Multiple logistic regression was utilized to examine the independent and combined effects of PA and depressive symptoms on the risk of prefrailty and frailty. The combined effects were visualized by marginal plots.

Results

The prevalence of prefrailty and frailty in older adults were 42.16% and 10.58%. Compared with the group of “Light physical activity and With depressive symptoms”, “Vigorous physical activity and Without depressive symptoms” had the lowest risk of prefrailty and frailty.

Conclusions

Older adults who do not engage in PA or have depressive symptoms increased the risk of frailty, but older adults with depressive symptoms could lower the risk of frailty through PA.

Relevance to Clinical Practice

It is effective to reduce the risk of frailty by directing older adults to do moderate physical activity, although they have depressive symptoms. The focus should also be on older adults with depressive symptoms, who have at least more than twice and fourfold risk of prefrailty and frailty compared to those without.

Impact

This study offers insights for future interventions aimed at preventing frailty in older adults.

Reporting Method

This study adhered to the STROBE checklist.

Patient or Public Contributions

Older adults participated in this study and completed questionnaires.

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