Accelerate aging meditates association between bowel dysfunction and depression severity

ABSTRACT Background Our 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. Methods The 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. Result A total of 11,808 participants were included in this study. Linear regression analysis showed that both diarrhea (β=3.73, 95% Confidence Interval (CI): 1.69-8.22, P=1.60×10-3) and depression severity (β=1.08, 95%CI: 1.06-1.09, P=4.61×10-16) were positively correlated with PAA. In addition, both constipation (β=2.76, 95%CI: 1.89-4.04, P=2.28×10 −6 ) and diarrhea (β=4.29, 95%CI: 2.65-6.95, P=2.11×10-7) 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 ≥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)