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Accelerate aging meditates association between bowel dysfunction and depression severity

Zhang, G.; Wang, X.; Wang, X.; Zhang, C.

2026-02-05 gastroenterology
10.64898/2026.02.04.26345571 medRxiv
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BackgroundOur study aimed to investigate the relationship between phenotypic age acceleration (PAA), bowel dysfunction (constipation, diarrhea), and depression severity, and examine whether phenotypic age acceleration can play a mediating role in bowel dysfunction and depression severity. MethodsThe data analysis of our study was conducted from the National Health and Nutrition Examination Survey (2005-2010). Participants with bowel dysfunction were identified on the questionnaire of bowel health. Depression was determined based on the Patient Health Questionnaire-9 (PHQ-9). The calculation of PAA is based on 9 test indicators and actual age; a higher PAA means accelerated aging. In this study, a weighted linear regression model was used to analyze the associations among defecation disorders, PAA, and depression. Restricted Cubic Spline (RCS) curves were applied to explore the potential non-linear relationships between the aforementioned variables. Additionally, a mediation effect model was employed to verify whether PAA could function as a mediating variable in the relationship between defecation disorders and depression. ResultA total of 11,808 participants were included in this study. Linear regression analysis showed that both diarrhea ({beta}=3.73, 95% Confidence Interval (CI): 1.69-8.22, P=1.60x10-3) and depression severity ({beta}=1.08, 95%CI: 1.06-1.09, P=4.61x10-16) were positively correlated with PAA. In addition, both constipation ({beta}=2.76, 95%CI: 1.89-4.04, P=2.28x10-6) and diarrhea ({beta}=4.29, 95%CI: 2.65-6.95, P=2.11x10-7) were positively correlated with depression severity. Further mediation effect analysis revealed that PAA may play a mediating role in the association between diarrhea and depression severity (the proportion of mediation effect in the total population was 7.2285%). When exploring whether PAA exerts a mediating role in the association between constipation and depression severity, it was found that PAA played a mediating role in female participants and participants aged <60 years, except for male participants and those aged [&ge;]60 years (the proportion of mediation effect was 9.8417% in females and 8.4512% in the population aged <60 years, with all relevant P-values <0.005)

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