Oxidative Stress in Vascular Aging: Therapeutic Potential of the Antioxidant Paradox. A State-of-the-Art Review

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with aging as one of its main risk factors. Cellular senescence and oxidative stress form a bidirectional vicious cycle that drives vascular aging, endothelial dysfunction, and atherosclerotic progression. This state-of-the-art review synthesizes current evidence on the interplay between oxidative stress and senescence in cardiovascular aging and critically assesses whether antioxidant strategies can benefit vascular health. A targeted literature search was conducted in PubMed/MEDLINE, Web of Science, and Scopus (2016-2026). While endogenous antioxidant defenses decline with age, exogenous antioxidants, including resveratrol, vitamins C and E, omega-3 fatty acids, carotenoids, and coenzyme Q10,demonstrate promising preclinical effects, yet large-scale clinical trials have yielded inconsistent results. The VITAL and STRENGTH trials failed to demonstrate significant cardiovascular benefit with omega-3 supplementation, and elevated serum β-carotene was found paradoxically associated with increased cardiovascular mortality. Emerging mitochondria-targeted antioxidants (MitoQ, MitoTEMPO) show preclinical promise but require further clinical validation. Current evidence does not support antioxidant supplementation for cardiovascular prevention. Lifestyle interventions, particularly antioxidant-rich dietary patterns such as the Mediterranean diet, remain the safest strategy. Future research should develop personalized approaches guided by oxidative stress biomarkers and long-term trials.