Cardiovascular aging as a modifiable biological process: Mechanisms, clinical phenotypes, and translational opportunities

Figure 1 Cardiovascular aging arises from interconnected molecular defects, including DNA damage, mitochondrial dysfunction, and nutrient-sensing imbalance leading to cellular senescence and chronic inflammation (senescence-associated secretory phenotype, inflammaging). These processes converge to cause vascular stiffness, fibrosis, and arrhythmia, ultimately manifesting as cardiovascular diseases. γ-H2AX: The phosphorylated form of histone H2AX; 8-oxo-dG: 8-hydroxy-2’-deoxyguanosine; mtROS: Mitochondrial reactive oxygen species; SIRT: Sirtuin (silent information regulator); PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; mTOR: Mechanistic target of rapamycin; AMPK: Adenosine 5’-monophosphate-activated protein kinase; SASP: Senescence-associated secretory phenotype; IL: Interleukin; TNF-α: Tumor necrosis factor α; MMP-9: Matrix metalloproteinase-9; ECs: Endothelial cells; VSMCs: Vascular smooth muscle cells; EF: Ejection fraction.