Clinical biomarker‐based biological aging and risk of benign prostatic hyperplasia: A large prospective cohort study

Abstract

Abstract Objective Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging‐related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera–Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM‐BAge and PhenoAge‐BAge measures based on the Levine method. The KDM‐AAge and PhenoAge‐AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results During a median follow‐up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000–1.223) for KDM‐AAge and 1.180 (95% CI, 1.068–1.303) for PhenoAge‐AAge, respectively. For PhenoAge‐AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374–2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088–1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge‐associated risk of BPH was independent of and additive to genetic risk. Conclusions Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

Keywords

• accelerated age
• aging
• benign prostatic hyperplasia
• biological age
• chronological age