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Vascular Aging: Implications for Cardiovascular Disease and Therapy
Yohannes T Ghebre1, Eduard Yakubov2, Wing Tak Wong3
1Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas, USA.
Insights
Aging significantly impacts cardiovascular health, causing blood vessel dysfunction and increasing the risk of heart disease in older adults. Understanding these age-related vascular changes is key to developing effective interventions.
Area of Science:
- Cardiovascular Science
- Gerontology
- Vascular Biology
Background:
- Cardiovascular disease (CVD) incidence and prevalence rise with age, linked to detrimental effects on the heart and vasculature.
- Aging is a significant CVD risk factor, characterized by structural and functional vascular changes, including increased oxidative stress and cellular senescence.
Purpose of the Study:
- To review the impact of aging on cardiovascular health.
- To highlight the cellular and molecular mechanisms underlying age-associated vascular changes.
- To discuss pharmacological interventions for preventing or delaying age-related CVD.
Main Methods:
- Literature review focusing on age-related vascular changes.
- Analysis of molecular and physiological mechanisms affecting the endothelium and vessel wall.
- Discussion of existing and potential therapeutic strategies.
Main Results:
- Advancing age leads to endothelial dysfunction, reduced release of vasodilators (e.g., nitric oxide), and increased production of vasoconstrictors and reactive oxygen species.
- These changes promote DNA damage, senescence, and vessel wall stiffening, contributing to hypertension, diabetes, and atherosclerosis.
- The balance of vasoactive molecules shifts, favoring harmful substances that damage tissues and impair vascular function.
Conclusions:
- Aging profoundly alters vascular structure and function, increasing CVD risk.
- Understanding the molecular basis of age-associated vascular dysfunction is crucial for therapeutic development.
- Pharmacological interventions hold promise for mitigating age-related cardiovascular decline.
Abstract:
The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function. Intriguingly, the vessel wall, a biochemically active structure composed of collagen, connective tissue, smooth muscle and endothelial cells, is adversely affected by processes involved in premature or normal aging. Notably, the inner most layer of the vessel wall, the endothelium, becomes senescent and dysfunctional with advancing age. As a result, its ability to release vasoactive molecules such as acetylcholine (ACh), prostacyclin (PGI2), endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO) is reduced and the cellular response to these molecules is also impaired. By contrast, the vascular endothelium increases its generation and release of reactive oxygen (ROS) and nitrogen (RNS) species, vasoconstrictors such as endothelin (ET) and angiotensin (AT), and endogenous inhibitors of NO synthases (NOSs) to block NO. This skews the balance of the endothelium in favor of the release of highly tissue reactive and harmful molecules that promote DNA damage, telomere erosion, senescence, as well as stiffened and hardened vessel wall that is prone to the development of hypertension, diabetes, atherosclerosis and other cardiovascular risk factors. This Review discusses the impact of advancing age on cardiovascular health, and highlights the cellular and molecular mechanisms that underlie age-associated vascular changes. In addition, the role of pharmacological interventions in preventing or delaying age-related cardiovascular disease is discussed.