AI 中文总结
本研究揭示生物衰老模型存在与健康状况相关的预测偏差，源于均值回归强度随健康状态变化，影响标志物解释，需谨慎使用并加强验证。
AI 中文摘要
生物衰老标志物已引起越来越多的关注，相关模型通过器官成像或血液生物标志物来估计年龄。估计年龄高于实际年龄或特定年龄人群的预期值，被认为反映了加速衰老和较差的健康状况。以往研究通过疾病与年龄差距或加速之间的正相关关系支持了这一假设。然而，在本研究中，我们发现了衰老标志物中普遍存在的与健康状况相关的预测偏差，这影响了它们的关键解释和应用。具体而言，我们研究了源自视网膜图像、脑部MRI、胸部X光片、腹部CT和血液检测的五种衰老标志物，并使用关联分析对其进行了评估。我们观察到四种基于器官图像的标志物存在公认的均值回归（RTM）现象，即估计年龄向训练队列的平均年龄偏移。更重要的是，我们揭示了RTM的强度随健康状况而变化，不健康个体的RTM比健康个体更强。这种差异性的RTM引入了与健康状况相关的预测偏差，该偏差在校准后仍然存在，并系统性地改变了各年龄亚组之间的关联，表明整个队列的关联可能无法反映个体年龄亚组内观察到的关联。此外，我们表明所测试的衰老标志物（包括源自血液生物标志物的PhenoAge）在个体水平上区分健康状况的能力有限。这些发现要求对生物衰老标志物及其在临床研究中的使用进行谨慎解读，并强调在衰老标志物能够可靠地为个体健康评估提供信息之前，需要进一步的发展和验证。
英文摘要
Biological ageing markers have attracted growing interest, with models estimating age from organ imaging or blood biomarkers. An estimated age above chronological age or the age-specific population expectation is assumed to reflect accelerated ageing and poorer health. Previous research has supported this assumption through positive associations between disease and age gaps or acceleration. However, in this study, we identified a widespread health-dependent prediction bias in ageing markers that affects their key interpretation and application. Specifically, we investigated five ageing markers derived from retinal images, brain MRI, chest radiographs, abdominal CT, and blood tests, and evaluated them using association analyses. We observed the well-recognised phenomenon of regression to the mean (RTM) in the four organ-image based markers, whereby estimated ages were shifted towards the mean age of the training cohort. More importantly, we revealed that the strength of RTM varied with health status, with stronger RTM in unhealthy than in healthy individuals. This differential RTM introduced a health-dependent prediction bias that persisted after calibration and systematically altered associations across age subgroups, suggesting that whole cohort associations may not reflect those observed within individual age subgroups. Additionally, we showed that the tested ageing markers, including PhenoAge derived from blood biomarkers, had limited ability to distinguish health status at the individual level. These findings call for careful interpretation of biological ageing markers and their use in clinical studies, and highlight the need for further development and validation before these ageing markers can reliably inform individual health assessments.
CommentsCode: https://github.com/HORIZONHealthcare/AG-RTM
