Papadam Anastasios, Lionikas Arimantas, Grassmann Felix
Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Institute for Clinical Research and Systems Medicine, Health and Medical University, Potsdam, Germany.
Aging Cell. 2025 May;24(5):e14473. doi: 10.1111/acel.14473. Epub 2025 Jan 5.
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.
年龄相关性黄斑变性(AMD)是一种进行性疾病,也是导致中心视力丧失的主要原因。年龄是最重要的风险因素,其次是遗传和吸烟。然而,衰老是一个复杂的过程,生物年龄在个体之间以及不同器官系统内可能与实际年龄有所偏差。最初,我们通过分析英国生物银行队列中的各种生理和身体指标,利用机器学习来预测免疫、心血管、肺、肾、肌肉骨骼、代谢和肝脏系统的生物年龄。然后,我们研究了每个器官的生物年龄与来自电子健康记录数据的AMD发病情况以及不同AMD遗传风险评分之间的关联。我们观察到,招募后发生AMD的参与者中,与对照组相比,大多数器官系统都显示出加速衰老,其中免疫系统受影响最大,尤其是在年轻男性中。令人惊讶的是,我们发现AMD患者的肝脏系统衰老速度比对照组慢,特别是在女性患者中。除心血管和肺外,总体AMD遗传风险评分与所有组织中更快的器官衰老相关,而按途径分层的遗传风险评分对每个器官系统的影响不同。总之,我们发现与AMD相关的器官衰老存在差异。重要的是,AMD的遗传风险变异与各种器官系统的差异衰老有关。