Proteomics mediates the effects of biological aging on the progression of cardio-renal-metabolic comorbidity: a UK biobank cohort study
Authors' conclusion
Biological aging was strongly associated with the progression of CRM comorbidity, and these associations were partly accounted for by specific circulating proteins. These findings highlight the potential of aging-centered strategies and proteomic biomarkers for improving the risk prediction of CRM health and identifying therapeutic targets.
Study context
- Population
- UK Biobank participants free of cardio-renal-metabolic (CRM) diseases (CVD, CKD, T2D) at baseline; proteomics subpopulation n = 35,118 with 2911 plasma proteins profiled
- Participants
- 330,177 participants
- Exposure
- Per SD increase in biological aging indicators
- Outcome
- CRM progression: transitions from no CRM disease to first, double and triple CRM diseases
Methodological detailsmultistate proportional hazards model, mediation analyses
- Multistate proportional hazards model
- Mediation analyses
Main finding
As reported in the abstract
Transition to first CRM disease, HR per SD PhenoAge
1.42
95% CI 1.40–1.44
Transition to double CRM disease, HR per SD PhenoAge
1.26
95% CI 1.22–1.31
Transition to triple CRM disease, HR per SD PhenoAge
1.24
95% CI 1.12–1.37
Observational data: associations, not effects.
Further findings
Proteomic mediation of biological aging–CRM progression associations
- Circulating key proteins statistically mediating the associations
- nine
- Largest mediated proportion (GDF15, ADM, HAVCR1)
- 13.10-43.23%
Original publication
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