Accelerated biological ageing is associated with a large drusen burden

PURPOSE: To investigate the association between accelerated biological ageing, measured by Phenotypic Age (PhenoAge) and PhenoAge Acceleration (PhenoAgeAccel), and features of early and intermediate age-related macular degeneration (AMD) in a population-based cohort. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey. Biological age was estimated using the PhenoAge algorithm, a composite of routine blood biomarkers and chronological age, and PhenoAgeAccel was defined as the residual from regression of PhenoAge on chronological age. Retinal outcomes were drusen ≥500 μm (primary outcome), drusen ≥125 μm and pigmentary abnormalities. Associations were evaluated using logistic regression adjusted for biological sex, race/ethnicity, smoking, body mass index and diabetes. RESULTS: A total of 5322 participants were included (mean age 59.4 ± 12.4 years; 50.4% female). Drusen ≥500 μm were present in 4.1%, drusen ≥125 μm in 10.2% and pigmentary abnormalities in 5.6%. PhenoAgeAccel > + 3 years was associated with higher odds of drusen ≥500 μm (OR: 1.56, 95%CI: 1.07-2.27, p = 0.022), whereas no association was observed for <-3 years. Each 1-year increase in PhenoAgeAccel was associated with higher odds of drusen ≥500 μm (OR: 1.02, 95%CI: 1.00-1.04, p = 0.022). PhenoAgeAccel > + 3 years was also associated with drusen ≥125 μm (OR: 1.29, 95%CI: 1.00-1.65, p = 0.049), but not with pigmentary abnormalities. CONCLUSION: Accelerated biological ageing was associated with increased drusen burden, but not pigmentary abnormalities, suggesting that early structural features of AMD may reflect broader systemic ageing processes.