Have a minute? Good because that might be all it takes to save your life. There are many biological processes that contribute to aging that includes changes at the cellular level that occurs as we mature. Some are inevitable as we age and there are many others that do not have to be a definitive part of our aging plan. There are wide varieties of conditions such as Atherosclerosis that contributes to excessive inflammatory and fibro-proliferative processes that will affect the arteries. Atherosclerosis kills about a half a million people every year. Yet such deaths can be avoided through developing effective therapies to prevent the transition from largely benign age-related vascular changes to pathological atherosclerotic degeneration. Efficient removal of DNA damage can prevent the initiation and progression of atherosclerosis by avoiding the development of vascular cell senescence and/or apoptosis.
Atherosclerosis is defined as being a degenerative disease of the arteries characterized by patchy thickening of the inner lining of the arterial walls, caused by deposits of fatty material (Collins English Dictionary, 2009). Aging and atherosclerosis have something in common and that is, they share several biochemical pathways and similar vascular alterations. Cellular senescence (process by which cells lose their ability to replicate after a finite number of cell divisions) is linked to the pathogenesis of atherosclerosis. Endothelial cells and vascular smooth muscle cells, both derived from human atherosclerotic plaques, show a lower rate of cell proliferation in vitro and undergo senescence earlier than cells from normal vessels (Maria Andreassi, 2008).
Consequently, every single person with atherosclerosis has endothelial dysfunction. A normal artery wall consists of three layers a thin smooth layer (tunica intima) that lines the inside of the artery that helps blood flow, a muscular elastic layer (tunica media) that helps the pulse circulates blood, and a tough outer layer (tunic adventitia) that protects the artery. Endothelial cells prevent toxic, blood-borne substances from penetrating the smooth muscle of the blood vessel. As we age many atherogenic factors, if left unchecked damages the delicate endothelial cells. Endothelial dysfunction allows lipids and toxins to penetrate the endothelial layer and enter smooth muscle cells. This results in the initiation of an oxidative and inflammatory process that starts the development of plaque deposits. The body tries to prevent the invasion of LDL-C from entering the artery walls by activating Macrophages to consume the LDL-C. The Macrophages become enlarged cholesterol enriched cells called Foam Cells that are embedded in the cell walls. The artery walls become saturated with Foam Cells known as Fatty Streaks in the vessel walls. As the Fatty Streaks grow, the body tries to protect the artery from them by surrounding them in the fibrous capsule and it is at this stage that the growth is called plaque.
Undoubtedly, DNA plays a pivot role in Atherosclerosis. DNA strands break and chromosomal damage presents itself in the circulating cells in individuals with Atherosclerosis. DNA damage is present in the human atherosclerotic plaque ranging from “macro” damage, including deletions or additions of whole chromosomes or parts of chromosomes, to “micro” damage, which includes loss of heterozygosity and micro-satellite instability (mutations in DNA regions that may
affect gene expression), DNA strands breaks and modifications of DNA (including oxidation) or DNA adducts, DNA adducts are covalent adducts between chemical mutagens, and DNA. Such couplings activate DNA repair processes, and unless repaired prior to DNA replication, may lead to nucleotide substitutions, deletions, and chromosome rearrangements, (Andreassi, 2008). The accumulation of DNA damage may be a critical mechanism, able to accelerate senescence of...
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