Differential Organ Ageing Is Associated With Age‐Related Macular Degeneration

ABSTRACT

Age‐related macular degeneration (AMD) is a progressive disorder and the leading cause of central vision loss. Age is the most important risk factor, followed by genetics and smoking. However, ageing is a complex process, and biological age can deviate from chronological age between individuals and within different organ systems. Initially, we used machine learning to predict the biological age of the immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic and hepatic systems by analysing various physiological and physical markers in the UK Biobank cohort. Then, we investigated the association of each organ's biological age with incident AMD derived from electronic health record data as well as with different AMD genetic risk scores. We observed that most organ systems in participants who developed AMD after recruitment showed accelerated ageing compared with controls, with the immune system being the most affected, especially in younger males. Surprisingly, we found that AMD patients showed slower ageing of their hepatic system compared to controls, particularly in female patients. The overall AMD genetic risk score was associated with faster organ ageing across all tissues except cardiovascular and pulmonary, while genetic risk scores stratified by pathways differently influenced each organ system. In conclusion, we found differential organ ageing associated with AMD. Significantly, genetic risk variants of AMD are associated with differential ageing of various organ systems.