Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases. Critical analysis of both preclinical and clinical studies reveals significant sex-specific variations in these mechanisms, which could be pivotal in understanding the disparity in disease morbidity and mortality between sexes. The review highlights key molecular pathways, including oxidative stress, inflammation, and autophagy, and their differential roles in the vascular aging of males and females. We argue that recognizing these sex-specific differences is crucial for developing targeted therapeutic strategies aimed at preventing and managing age-related vascular pathologies. The implications for personalized medicine and potential areas for future research are also explored, emphasizing the need for a nuanced approach to the study and treatment of vascular aging.
Keywords: Atherosclerosis; Cellular senescence; Endocrine; Ischemic heart disease; Menopause; Sex differences; Sexual dimorphism; Vascular aging; Vascular cognitive impairment.
© 2025. The Author(s), under exclusive licence to American Aging Association.