Proteome organ aging and cardiometabolic risk in a population at risk for heart failure.

Qu K, Dal Canto E, van Ommen ALN, Kamar SA, Teske AJ, Cramer MJ, Verhaar MC, Duncker DJ, Rutten FH, Kardys I, Menken R, Hofstra L, Tulevski II, Somsen GA, Onland-Moret NC, Benavente ED, den Ruijter HM. Proteome organ aging and cardiometabolic risk in a population at risk for heart failure. Cardiovasc Diabetol. 2025 Nov 12;24(1):430. doi: 10.1186/s12933-025-02980-6. PMID: 41225469; PMCID: PMC12613572.

Biological aging differs across organs and individuals and may contribute to the development and progression of heart failure. Using plasma proteomics, we estimated biological aging of the heart, arteries, and kidneys and examined its relationship with heart failure severity, cardiac function, and cardiometabolic risk factors, with a focus on sex differences. Accelerated heart aging was associated with more advanced heart failure in both women and men, whereas accelerated arterial aging showed a significant association only in women. Individuals with accelerated aging affecting multiple organs were more likely to have advanced heart failure. Heart aging was also linked to adverse cardiac structural and functional changes, with some sex-specific patterns. Diabetes emerged as an important factor associated with arterial and kidney aging, while the triglyceride-glucose body mass index was specifically associated with accelerated kidney aging in women. These findings suggest that organ-specific biological aging, particularly when involving multiple organs, is closely related to heart failure severity and highlight sex-specific differences in the cardiometabolic determinants of organ aging.