Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease

Abstract

Advancing age promotes cardiovascular disease (CVD), the leading cause of death in the United States and many developed nations. Two major age-related arterial phenotypes, large elastic artery stiffening and endothelial dysfunction, are independent predictors of future CVD diagnosis and likely are responsible for the development of CVD in older adults. Not limited to traditional CVD, these age-related changes in the vasculature also contribute to other age-related diseases that influence mammalian healthspan and potential lifespan. This review explores mechanisms that influence age-related large elastic artery stiffening and endothelial dysfunction at the tissue level via inflammation and oxidative stress, and at the cellular level via Klotho and energy sensing pathways (AMPK, Sirtuins, mTOR). We also discuss how long-term calorie restriction, a healthspan and lifespan extending intervention, can prevent many of these age-related vascular phenotypes through the prevention of deleterious alterations in these mechanisms. Lastly, we discuss emerging novel mechanisms of vascular aging, including senescence and genomic instability within cells of the vasculature. As the population of older adults steadily expands, elucidating the cellular and molecular mechanisms of vascular dysfunction with age is critical to better direct appropriate and measured strategies that utilize pharmacological and lifestyle interventions to prevent against CVD risk within this population.

Peculiarities of Age Vegetology of Men in Young and Middle Age

“…Розлади ВНС були описані при багатьох захворюваннях [9,10] і можуть бути первинними або вторинними по відношенню до них. Кількість хронічних захворювань, таких як цукровий діабет, гіпертонія та артрит зростає у всьому світі і їх патогенез пов'язують також з дисфункцією ВНС.…”

“…Хронічні захворювання зазвичай починаються зі змін у вегетативних функціях і навпаки, їх дисфункція може призвести до захворюваності та смертності від хронічних захворювань, які прогресують з віком. І звичайно старіння людини також пов'язане зі змінами у вегетативних функціях [9,10,11,12].…”

Inflammation as a mediator of arterial ageing

“…In addition to the SASP, senescent cells also produce reactive oxygen species [ROS; particularly superoxide anion (O 2 − ) and hydrogen peroxide (H 2 O 2 )]. This is important because elevated ROS have been implicated as a major contributor to arterial ageing, primarily by decreasing the bioavailability of NO (Donato, Machin, & Lesniewski, 2018;Seals, 2014). Reactive oxygen species also induce activation of NF B and subsequent inflammation (Schreck, Albermann, & Baeuerle, 1992), linking these two key processes in arterial ageing ( Figure 1).…”

Sex differences in vascular aging in response to testosterone

“…The reasons for the sex disparity in CVD are not completely understood but may be related to sex differences in vascular aging, a key mechanism in the etiology of age-associated CVD [2]. The phenotypic features of vascular aging include endothelial dysfunction and large elastic artery stiffening [2,3]. Endothelial dysfunction is characterized by reduced endothelialdependent vasodilation, due in large part to a decrease in the bioavailability of nitric oxide (NO) [4].…”