Surgical exposure and biological aging: A population-based study from the UK Biobank.

BACKGROUND: Surgical procedures are essential interventions for treating disease and saving lives. However, their relationship with biological age remains unclear. METHODS: This cross-sectional analysis included up to 472,279 UK Biobank participants. Surgical exposure was defined as surgical procedures occurring within 1, 3, and 5 years before baseline. Biological aging was assessed using PhenoAge acceleration, defined as the residual from regressing PhenoAge derived from multiple clinical biomarkers on chronological age, and leukocyte telomere length (LTL), measured using a validated qPCR method. Multivariable linear regression models were used to assess the associations between the number of surgeries and biological aging markers. Subgroup analyses assessed effect modification by age, frailty, comorbidity burden, and depression. RESULTS: After full adjustment, each additional surgery within 1, 3, and 5 years was associated, on average, with 0.46 (95% CI, 0.43-0.49), 0.26 (95% CI, 0.24-0.27), and 0.20 (95% CI, 0.19-0.21) years higher PhenoAge acceleration, respectively (all P < 0.001). For LTL, the corresponding fully adjusted β (95%CI) were - 0.002(-0.009 to 0.006), -0.003(-0.007 to 0.001), and - 0.002(-0.005 to 0.001) SD, respectively. Surgical exposure was more strongly associated with PhenoAge acceleration among individuals undergoing moderate to high stress surgeries (P for heterogeneity <0.001) and among those with frailty or greater comorbidity burden (P for interaction <0.001). CONCLUSION: Cumulative surgical exposure was associated with modest but detectable differences in PhenoAge acceleration, with associations varying according to surgical burden, surgical timing, and baseline physiological reserve.