Tian Yixing, Wang Jinqi, Zhu Tianyu, Li Xia, Zhang Haiping, Zhao Xiaoyu, Yang Xinghua, Luo Yanxia, Tao Lixin, Wu Zhiyuan, Guo Xiuhua
Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China.
Department of Mathematics and Statistics, La Trobe University, Melbourne 3086, Australia.
Nutrients. 2025 May 24;17(11):1783. doi: 10.3390/nu17111783.
Previous studies have confirmed that biological age (BA) acceleration is associated with single cardio-renal-metabolic diseases (CRMDs), typically including type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease. However, its association with progression to cardio-renal-metabolic multimorbidity (CRMM, coexistence of ≥2 CRMDs) and subsequent mortality remains unexplored.
Using the multi-state model, we analyzed 278,927 UK Biobank participants free of CRMDs at baseline to investigate the association between BA acceleration-measured by phenotypic age (PhenoAge) and Klemera-Doubal method age (KDMAge)-and CRMM progression trajectory, from health to the first CRMD and then to CRMM and death. BA acceleration was the residual from regressing BA on chronological age; positive values indicated a biologically older individual.
PhenoAge acceleration showed stronger associations than KDMAge acceleration. Per the 1-SD increase in PhenoAge acceleration; HRs (95% CIs) were observed at 1.18 (1.17-1.19) for baseline to first CRMD; 1.24 (1.22-1.26) for first CRMD to CRMM; 1.25 (1.22-1.27) for baseline to death; 1.13 (1.11-1.15) for first CRMD to death; and 1.09 (1.06-1.12) for CRMM to death. Biologically older individuals by PhenoAge acceleration showed greater reductions in CRMD-free and total life expectancy than those by KDMAge acceleration. Age, socioeconomic status, education, smoking status, alcohol consumption, physical activity, and diet-modified risks for specific transitions.
BA acceleration, particularly PhenoAge acceleration, relates to higher CRMM progression risk and shorter life expectancy. Combining BA acceleration with sociodemographic or lifestyle factors improves risk identification for specific transitions. BA acceleration offers the potential to guide CRMM prevention across its entire progression.
既往研究已证实生物年龄（BA）加速与单一的心肾代谢疾病（CRMD）相关，通常包括2型糖尿病、心血管疾病和慢性肾脏病。然而，其与进展为心肾代谢多病共存（CRMM，≥2种CRMD并存）及随后死亡率的关联仍未得到探索。
我们使用多状态模型，分析了278,927名英国生物银行的参与者，这些参与者在基线时无CRMD，以研究通过表型年龄（PhenoAge）和克莱梅拉-杜巴尔方法年龄（KDMAge）测量的BA加速与CRMM进展轨迹之间的关联，从健康状态到首次CRMD，再到CRMM和死亡。BA加速是BA对实足年龄回归后的残差；正值表明个体生物学年龄较大。
PhenoAge加速比KDMAge加速显示出更强的关联。PhenoAge加速每增加1个标准差；从基线到首次CRMD的风险比（HRs，95%置信区间）为1.18（1.17 - 1.19）；从首次CRMD到CRMM的为1.24（1.22 - 1.26）；从基线到死亡的为1.25（1.22 - 1.27）；从首次CRMD到死亡的为1.13（1.11 - 1.15）；从CRMM到死亡的为1.09（1.06 - 1.12）。与KDMAge加速相比，PhenoAge加速显示生物学年龄较大的个体在无CRMD和总预期寿命方面的降低幅度更大。年龄、社会经济地位、教育程度、吸烟状况、饮酒量、身体活动和饮食会改变特定转变的风险。
BA加速，尤其是PhenoAge加速，与更高的CRMM进展风险和更短的预期寿命相关。将BA加速与社会人口学或生活方式因素相结合可改善特定转变的风险识别。BA加速为指导CRMM在其整个进展过程中的预防提供了潜力。
