Accelerated biological ageing is associated with a large drusen burden

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.

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.

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.

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.