Mechanisms of Vascular Aging

Abstract

Aging of the vasculature plays a central role in morbidity and mortality of older people. In order 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 micro- and macrovascular diseases associated with old age. The importance of pro-geronic and anti-geronic 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.

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

“…Studies support that mtROS contribute to the inflammation in the cardiovascular system [17]. mtROS activate the redoxsensitive mediator, nuclear factor-κB (NF-κB), which regulates the transcription of various proinflammatory cytokines 2 Oxidative Medicine and Cellular Longevity [11,18]. As the heart ages, prolonged exposure to high levels of oxidants leads to the activation of NF-κB-mediated inflammation.…”

“…Enzymes of the electron transport system reside on the inner mitochondrial membrane (IMM), encompassing the mitochondrial matrix containing mtDNA. Excessive mitochondrial reactive oxygen species (mtROS) can damage DNA [11,12]. The mtDNA damage, which reduces the stabilization of adequate ATP supply during cardiac aging, disrupts the balance of cellular apoptosis, mitochondrial bioenergetics, and biogenesis.…”

Zonation-dependent single-endothelial cell transcriptomic changes in the aged brain

“…Altered energy metabolism may also be a key contributor to brain endothelial ageing 42 . We found that respiratory electron transport chain / ATP synthesis (e.g.…”

SIRT1 and Gender Differences in Atherosclerotic Cardiovascular Disease

“…Aging-induced functional and structural changes of vasculatures contribute to the pathogenesis of a wide range of age-related diseases, including ASCVD. Cellular senescence is a fundamental aging process wherein cells, including vascular endothelial and smooth muscle cells (vascular senescence 4) ), permanently withdraw from the cell cycle in response to a range of endogenous and exogenous stressors and undergo distinctive phenotypic alterations, including profound pro-inflammatory secretome changes 5) .…”