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Biological Age Acceleration Associated with the Progression Trajectory of Cardio-Renal-Metabolic Multimorbidity: A
Yixing Tian1, Jinqi Wang1, Tianyu Zhu1
1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, China.
Insights
Biological age acceleration, especially PhenoAge acceleration, is linked to increased risk of developing multiple cardio-renal-metabolic diseases (CRMM) and reduced life expectancy. Combining biological age with lifestyle factors enhances risk prediction for CRMM progression.
Area of Science:
- Gerontology and Public Health
- Cardiovascular and Renal Medicine
- Metabolic Disease Research
Background:
- Biological age (BA) acceleration is associated with individual cardio-renal-metabolic diseases (CRMDs).
- The link between BA acceleration and progression to cardio-renal-metabolic multimorbidity (CRMM) and mortality is not well understood.
Purpose of the Study:
- To investigate the association between BA acceleration and the progression trajectory to CRMM and death.
- To compare the predictive power of PhenoAge acceleration and Klemera-Doubal method age acceleration (KDMAge) for CRMM progression and mortality.
Main Methods:
- Analysis of 278,927 UK Biobank participants using a multi-state model.
- Measurement of BA acceleration using phenotypic age (PhenoAge) and Klemera-Doubal method age (KDMAge) as residuals from chronological age.
- Investigation of transitions from health to first CRMD, then to CRMM, and finally to death.
Main Results:
- PhenoAge acceleration demonstrated stronger associations with CRMM progression and mortality than KDMAge acceleration.
- Increased PhenoAge acceleration (1-SD) was associated with higher hazard ratios for transitions to first CRMD, CRMM, and death.
- Biologically older individuals by PhenoAge acceleration experienced greater reductions in CRMD-free and total life expectancy.
Conclusions:
- BA acceleration, particularly PhenoAge acceleration, is a significant predictor of CRMM progression and reduced life expectancy.
- Integrating BA acceleration with sociodemographic and lifestyle factors improves the identification of individuals at risk for CRMM.
- BA acceleration holds potential for guiding CRMM prevention strategies throughout its developmental stages.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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