Biological age (BA) is a marker to accurately assess aging, facilitating the prediction of age-related diseases and promoting healthy aging. In recent years, first- and second-generation organ-system-specific BA has been developed using chronological age (CA) or aging-related outcomes (mortality) as training phenotypes and data from questionnaires, physical examinations, clinical biochemistry, imaging, and multi-omics to investigate the specificity of organ systems aging. Here, we review the methodologies for constructing BA, current efforts to assess organ system-specific BA, and related genome-wide association studies (GWAS). Previous studies predominantly used the first-generation BA method, using CA as training phenotypes. Organ-system-specific BA can accurately predict the disease risk of corresponding organ systems. We propose the development of organ system-specific BA through second-generation BA models and conducting GWAS and Mendelian randomization studies to explore organ system-specific aging processes, which will provide a theoretical foundation for the clinical application of organ system-specific BA.
生物学年龄可实现对衰老程度的精准评估，预测年龄相关疾病风险，推动“健康老龄化”的实现。近年来，研究者基于问卷调查信息、体格检查指标、临床生化、影像检查和多组学等数据，以实足年龄或衰老相关结局（如死亡）为训练表型，构建第一、二代器官系统特异性生物学年龄，探究器官系统的衰老特异性。本文简要回顾生物学年龄的构建方法，详细介绍器官系统特异性生物学年龄研究进展及其全基因组关联研究（GWAS）进展。既往研究构建方法主要是第一代生物学年龄，以实足年龄为训练表型。器官系统特异性生物学年龄有助于精准预测相应器官系统疾病风险。本文提出展望，利用第二代生物学年龄方法构建器官系统特异性生物学年龄，利用GWAS方法与孟德尔随机化研究方法探索器官系统特异性衰老进程，为器官系统特异性生物学年龄的临床应用提供理论基础。.