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

Vollständiger Abstract

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Cardiovascular aging, a primary driver of the increasing prevalence of cardiovascular disease in older adults, involves a complex biological basis beyond mere chronological age. From a geroscience perspective, aging is now understood as a dynamic and potentially modifiable process, believed to be governed by interconnected molecular hallmarks such as cellular senescence, mitochondrial dysfunction, epigenetic remodeling, telomere attrition, and impaired proteostasis. This review synthesizes recent advancements in aging biology, illustrating how these core hallmarks appear to converge on major cardiovascular phenotypes including atherosclerosis, heart failure with preserved ejection fraction, hypertension, and arrhythmia through shared mechanisms. These mechanisms encompass endothelial dysfunction, vascular smooth muscle cell phenotypic switching, myocardial fibrosis, chronic inflammation, and electrophysiological instability. We also summarize current approaches to assessing cardiovascular aging, which include imaging-based indices, circulating biomarkers, and emerging epigenetic clocks capable of quantifying biological age and age acceleration. At the interventional level, growing preclinical and early-phase clinical evidence suggests that geroprotective strategies show promise for altering cardiovascular aging trajectories. These strategies include lifestyle modification, metabolic regulation, senotherapeutics, and modulation of mechanistic target of rapamycin and nicotinamide adenine dinucleotide pathways. Nevertheless, significant challenges persist, such as the absence of standardized aging assessment frameworks, uncertainties regarding long-term safety, and the necessity for rigorously designed clinical trials with aging-related endpoints. By connecting the molecular hallmarks of aging with clinically measurable cardiovascular phenotypes and novel therapeutic strategies, this review underscores cardiovascular aging as a clinically tractable and translationally relevant model for transforming geroscience principles into actionable approaches for disease prevention and healthy longevity.