Aging of the vasculature plays a central role in morbidity and mortality of older
people. To develop novel treatments for amelioration of unsuccessful vascular aging
and prevention of age-related vascular pathologies, it is essential to understand
the cellular and functional changes that occur in the vasculature during aging. In
this review, the pathophysiological roles of fundamental cellular and molecular mechanisms
of aging, including oxidative stress, mitochondrial dysfunction, impaired resistance
to molecular stressors, chronic low-grade inflammation, genomic instability, cellular
senescence, epigenetic alterations, loss of protein homeostasis, deregulated nutrient
sensing, and stem cell dysfunction in the vascular system are considered in terms
of their contribution to the pathogenesis of both microvascular and macrovascular
diseases associated with old age. The importance of progeronic and antigeronic circulating
factors in relation to development of vascular aging phenotypes are discussed. Finally,
future directions and opportunities to develop novel interventions to prevent/delay
age-related vascular pathologies by targeting fundamental cellular and molecular aging
processes are presented.
