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Model Systems to Study the Mechanism of Vascular Aging
Janette van der Linden1,2, Lianne Trap3,4, Caroline V Scherer2
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, 3015 GD Rotterdam, The Netherlands.
Insights
Arterial aging, a key part of cardiovascular aging, involves structural and functional changes in blood vessels. Genomic instability accelerates this process, impacting overall cardiovascular health.
Area of Science:
- Cardiovascular Science
- Aging Research
- Genetics
Background:
- Cardiovascular diseases are the leading global cause of mortality.
- Arterial aging involves significant structural and functional changes, contributing to cardiovascular decline.
- Genomic instability, caused by DNA damage accumulation, accelerates vascular aging.
Purpose of the Study:
- To explore the mechanisms and implications of arterial aging.
- To highlight the role of genomic instability in vascular aging.
- To review current models for studying vascular aging.
Main Methods:
- Review of existing literature on cardiovascular aging and genomic instability.
- Analysis of cellular and molecular changes associated with arterial aging.
- Examination of various in vivo, in vitro, and microfluidic models.
Main Results:
- Arterial aging is characterized by diminished stress response, increased luminal diameter, intimal/medial thickening, endothelial dysfunction, cellular senescence, and matrix remodeling.
- Genomic instability, exemplified by progeria syndromes, significantly accelerates vascular aging.
- Diverse models, including vessels-on-a-chip, are crucial for understanding vascular aging.
Conclusions:
- Arterial aging is a complex process with profound impacts on cardiovascular health.
- Genomic instability is a critical factor driving vascular aging.
- Advanced research models are essential for future studies in vascular aging.
Abstract:
Cardiovascular diseases are the leading cause of death globally. Within cardiovascular aging, arterial aging holds significant importance, as it involves structural and functional alterations in arteries that contribute substantially to the overall decline in cardiovascular health during the aging process. As arteries age, their ability to respond to stress and injury diminishes, while their luminal diameter increases. Moreover, they experience intimal and medial thickening, endothelial dysfunction, loss of vascular smooth muscle cells, cellular senescence, extracellular matrix remodeling, and deposition of collagen and calcium. This aging process also leads to overall arterial stiffening and cellular remodeling. The process of genomic instability plays a vital role in accelerating vascular aging. Progeria syndromes, rare genetic disorders causing premature aging, exemplify the impact of genomic instability. Throughout life, our DNA faces constant challenges from environmental radiation, chemicals, and endogenous metabolic products, leading to DNA damage and genome instability as we age. The accumulation of unrepaired damages over time manifests as an aging phenotype. To study vascular aging, various models are available, ranging from in vivo mouse studies to cell culture options, and there are also microfluidic in vitro model systems known as vessels-on-a-chip. Together, these models offer valuable insights into the aging process of blood vessels.
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