Abstract
OBJECTIVE: To investigate the relationship between leukocyte telomere length (LTL), a biomarker of cellular aging, and both the incidence and severity of age-related cataract (ARC) across cohorts from the UK and China. METHODS: The multicenter, multiethnic cohort study involved 122,932 healthy individuals with a mean age of 56.27 years from the UK Biobank, a community-based cohort, and 53 cataract patients with a mean age of 71.74 years from a hospital-based cohort in China. LTL was measured using validated polymerase chain reaction techniques. ARC was assessed using a combination of self-reported data, medical records, and operation codes. In the Chinese cohort, lens morphological features and opacities were evaluated using Scheimpflug imaging. Associations between LTL and ARC were analyzed using Cox proportional hazards models, logistic regression, and restricted cubic splines. A phenome-wide association study (PheWAS) was conducted to validate the association between LTL and cataract in the UK Biobank cohort. RESULTS: Over a median follow-up time of 11.18 years, 4,089 incident ARC cases were documented in the UK cohort. Longer LTL was associated with a lower incidence of ARC [hazard ratio (HR) = 0.93, 95% confidence interval (CI): 0.91 to 0.96; P < 0.001]. Restricted cubic splines indicated an L-shaped association between LTL and ARC (P for nonlinearity = 0.03), where ARC risk decreased with longer LTL until a threshold before plateauing. The PheWAS provided support for the association between LTL and cataract (P = 2.36 × 10⁻⁶) across 1,011 phecodes in the UK Biobank. In the Chinese cohort, LTL was negatively correlated with average lens density (β = - 0.32, 95% CI: - 0.61 to - 0.04; P = 0.03). CONCLUSIONS: Longer LTL is associated with a reduced risk and severity of ARC, suggesting shared biological pathways between telomere attrition and lens aging. This supports the lens as a unique window for studying systemic aging and LTL as an index of modifiable health behaviors influencing cataract development.