Mechanisms Involved in the Aging-Induced Vascular Dysfunction

Abstract

Vascular aging is a key process determining health status of aged population. Aging is an independent cardiovascular risk factor associated to an impairment of endothelial function, which is a very early and important event leading to cardiovascular disease. Vascular aging, formerly being considered an immutable and inexorable risk factor, is now viewed as a target process for intervention in order to achieve a healthier old age. A further knowledge of the mechanisms underlying the age-related vascular dysfunction is required to design an adequate therapeutic strategy to prevent or restore this impairment of vascular functionality. Among the proposed mechanisms that contribute to age-dependent endothelial dysfunction, this review is focused on the following aspects occurring into the vascular wall: (1) the reduction of nitric oxide (NO) bioavailability, caused by diminished NO synthesis and/or by augmented NO scavenging due to oxidative stress, leading to peroxynitrite formation (ONOO−); (2) the possible sources involved in the enhancement of oxidative stress; (3) the increased activity of vasoconstrictor factors; and (4) the development of a low-grade pro-inflammatory environment. Synergisms and interactions between all these pathways are also analyzed. Finally, a brief summary of some cellular mechanisms related to endothelial cell senescence (including telomere and telomerase, stress-induced senescence, as well as sirtuins) are implemented, as they are likely involved in the age-dependent endothelial dysfunction, as well as in the lower vascular repairing capacity observed in the elderly. Prevention or reversion of those mechanisms leading to endothelial dysfunction through life style modifications or pharmacological interventions could markedly improve cardiovascular health in older people.

Telomere length in circulating leukocytes is associated with lung function and disease

“…Whereas our findings for asthma are novel, the results for COPD are in line with previous findings in case-control [14][15][16][17] and population-based studies [18]. This suggests that, as already shown for other chronic diseases [1,3,35], accelerated ageing may contribute to the pathogenesis of asthma and COPD.…”

The role of hydrogen sulfide in diastolic function restoration during aging

“…Excess NO when interacting with • О 2 -promotes generation of a toxic compound, ONOO -, possessing the wide range of damaging actions -from LPO, inactivation of enzymes and ion channels to inhibition of mitochondrial respiration. Peroxynitrite decomposes to form NO 3 - [36,37]. The pools of the latter in the heart homogenate of old animals exceeded the control value 6.4 times.…”

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“…Основу порушення ендотелійзалежного розслаблення судин при старінні становить зниження вмісту NO, яке зумовлене такими патофізіологічними механізмами, як окис-ний стрес, зростання активності ренінан-гіотензинової системи, неспряження cNOS, підвищення активності вазоконстрикторних факторів тощо [4].…”

“…рис. 3) або зниження пулів кофактора cNOS -тетрагідробіоптерину (BH 4 ), в результаті його окиснення радикалом * О 2 -або пероксинітритом (ONOO -) [4]. Нами було встановлено достовірне посилення ге-нерації супероксиду (див.…”