Inflammaging and Senescence-Driven Extracellular Matrix Remodeling in Age-Associated Cardiovascular Disease

Cardiovascular aging is a multifactorial and systemic process that contributes significantly to the global burden of cardiovascular disease, particularly in older populations. This review explores the molecular and cellular mechanisms underlying cardiovascular remodeling in age-related conditions such as hypertension, atrial fibrillation, atherosclerosis, and heart failure. Central to this process are chronic low-grade inflammation (inflammaging(definition)), oxidative stress, cellular senescence(definition), and maladaptive extracellular matrix remodeling. These telomere(definition) attrition, cellular senescence)." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">hallmarks of aging(definition) interact to impair endothelial function, promote fibrosis, and compromise cardiac and vascular integrity. Key molecular pathways-including the renin-angiotensin-aldosterone system, NF-κB, NLRP3 inflammasome, IL-6, and TGF-β signaling-contribute to the transdifferentiation of vascular cells, immune dysregulation, and progressive tissue stiffening. We also highlight the role of the senescence-associated secretory phenotype and mitochondrial dysfunction(definition) in perpetuating inflammatory and fibrotic cascades. Emerging molecular therapies offer promising strategies to reverse or halt maladaptive remodeling. These include senescence-targeting agents (senolytics(definition)), Nrf2 activators, RNA-based drugs, and ECM-modulating compounds such as MMP inhibitors. Additionally, statins and anti-inflammatory biologics (e.g., IL-1β inhibitors) exhibit pleiotropic effects that extend beyond traditional risk factor control. Understanding the molecular basis of remodeling is essential for guiding future research and improving outcomes in older adults at risk of CVD.