Background/aims To identify the metabolic underpinnings of retinal aging and examine how it is related to mortality and morbidity of common diseases. Methods The retinal age gap has been established as essential aging indicator for mortality and systemic health. We applied neural network to train the retinal age gap among the participants in UK Biobank and used nuclear magnetic resonance (NMR) to profile plasma metabolites. The metabolomic signature of retinal ageing (MSRA) was identified using an elastic network model. Multivariable Cox regressions were used to assess associations between the signature with 12 serious health conditions. The participants in Guangzhou Diabetic Eye Study (GDES) cohort were analyzed for validation. Results This study included 110 722 participants (mean age 56.5±8.1 years at baseline, 53.8% female), and 28 plasma metabolites associated with retinal ageing were identified. The MSRA revealed significant correlations with each 12 serious health conditions beyond traditional risk factors and genetic predispositions. Each SD increase in MSRA was linked to a 24%–76% higher risk of mortality, cardiovascular diseases, dementia and diabetes mellitus. MSRA showed dose–response relationships with risks of these diseases, with seven showing non-linear and five showing linear increases. Validation in the GDES further established the relation between retinal ageing-related metabolites and increased risks of cardiovascular and chronic kidney diseases (all p<0.05). Conclusions The metabolic connections between ocular and systemic health offer a novel tool for identifying individuals at high risk of premature ageing, promoting a more holistic view of human health. All data used in this study are available from UK Biobank via data access procedures (). Permission to use the UK Biobank Resource was obtained via material transfer agreement as part of Application 105658. Not applicable.

中文翻译：

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视网膜衰老、多基因易感性和主要健康结局的代谢组学特征


背景/目标 确定视网膜衰老的代谢基础，并检查它与常见疾病的死亡率和发病率有何关系。方法 视网膜年龄差距已被确定为死亡率和全身健康的重要衰老指标。我们应用神经网络来训练英国生物样本库参与者之间的视网膜年龄差距，并使用核磁共振 （NMR） 来分析血浆代谢物。使用弹性网络模型确定视网膜衰老的代谢组学特征 （MSRA）。多变量 Cox 回归用于评估特征与 12 种严重健康状况之间的关联。对广州糖尿病眼研究 （GDES） 队列的参与者进行分析以进行验证。结果 本研究包括 110 722 名参与者 （基线时平均年龄 56.5±8.1 岁，53.8% 为女性），确定了 28 种与视网膜衰老相关的血浆代谢物。MSRA 揭示了除传统风险因素和遗传易感性之外，每 12 种严重健康状况都存在显著相关性。MSRA 的每一次 SD 增加都与死亡、心血管疾病、痴呆和糖尿病风险增加 24%-76% 有关。MSRA 显示剂量反应与这些疾病的风险呈关系，其中 7 项显示非线性，5 项显示线性增加。GDES 的验证进一步确定了视网膜衰老相关代谢物与心血管和慢性肾病风险增加之间的关系 （均 p<0.05）。结论 眼部和全身健康之间的代谢联系为识别过早衰老高风险的个体提供了一种新工具，促进了对人类健康的更全面认识。本研究中使用的所有数据都可以通过数据访问程序从英国生物银行获得 （）。 作为申请105658的一部分，通过材料转让协议获得使用英国生物样本库资源的许可。不適用。