A Short Tour of Scientific Thought on Vascular Aging

The aging of the vasculature, set aside from any other part of the body, arguably kills the largest fraction of humanity at the present time. It isn't just the dysfunctions of macrophages that lead to atherosclerotic plaque, and the narrowing of blood vessels and stroke and heart attack. It isn't just the declining density of capillary networks, reducing blood supply to energy-hungry tissues. It isn't just blood-brain barrier leakage and the consequent inflammation of the brain, or the stiffening of arteries that causes hypertension and remodeling of the heart. The vasculature is so vital that a great many mechanisms compete in their ability to cause harm with advancing age and the growing burden of cell and tissue damage.

Aging represents the main risk factor for cardiovascular disease (CVD) which carries the highest burden for the older population and is the leading cause of death worldwide. Vascular aging is a gradually developing process characterized by alterations in the properties of the vascular wall that start very early in life. In fact, it has been documented that the architecture of the vascular system is programmed in utero and most of the elastin, the major structural component underlying arterial wall elasticity, is synthesized and deposited during that period.

The phenotype of vascular aging in adults will be identified by certain vascular alterations which result in vascular dysfunction and development of a wide range of age-related vascular pathologies. These alterations are divided into structural changes which include the progressive thickening of the vascular wall along with vascular smooth muscle cell (VSMC) migration and proliferation, namely vascular remodeling, and the functional changes which include endothelial dysfunction, loss of arterial elasticity and reduced arterial compliance, all of which result in increased arterial stiffness.

The pathogenesis behind these changes in vascular aging involves multiple complex cellular and molecular mechanisms such as mitochondrial dysfunction and oxidative stress, inflammation, loss of proteostasis, genomic instability, cellular senescence, increased apoptosis and necroptosis, epigenetic alterations, and extracellular matrix (ECM) remodeling. As many age-related cardiovascular and cerebrovascular diseases are due to alterations in vascular function or are exacerbated by vascular functional and structural changes, it is important to thoroughly elucidate those fundamental pathophysiological mechanisms underlying the vascular aging process, in an attempt to develop novel treatments to reduce age-associated mortality. In this review, we describe the fundamental cellular and molecular mechanisms of aging: oxidative stress, chronic low-grade inflammation, cell matrix injury, epigenetic alterations, telomere length, cellular senescence and autophagy, considering in vitro and in vivo preclinical research and clinical studies.

Link: https://doi.org/10.3390/ijms23158672

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