The balance of evidence for the aging of the cardiovascular system suggests the following view. It starts off in the blood vessels, with the accumulation of senescent cells and cross-links. Cross-links directly stiffen these tissues, while senescentcells produce inflammation and changes in cell behavior that promote calcification - again leading to stiffness. These and other processes also disrupt the delicate balance of cell signaling responsible for blood vessel constriction and relaxation. All
At the same time as this is going on, increased oxidation in the lipids carried by the bloodstream is produced as a result of greater inflammation, or via processes such as cells becoming taken over by damaged mitochondria. Blood vessel walls becomeirritated by oxidized lipids, and that produces a feedback loop in which inflammatory signaling draws in cells that attempt to clean up the problem compounds, but fail and die, adding their remains to a growing fatty plaque that narrows and weakens the
This lightly sketched overview touches on a number of the root causes of aging outlined in the SENS rejuvenation research portfolio. It doesn't, however, mention amyloid, the solid deposits of misfolded or damaged proteins that appear in old tissues,and which are known to contribute to a range of age-related conditions. Yet we now know that transthyretin amyloid is implicated in some fraction of cardiovascular mortality, and appears to be the majority cause of death in supercentenarians, their
Quote:are highly associated with aging. However, few studies have focused on the relationship between amyloidosis and arterial diseases. Amyloidosis is a disorder of protein metabolism characterized by extracellular accumulation of abnormal insoluble amyloid
Amyloid is found in the aortic walls of almost 100% of the population above 50 years of age, and also aged people are susceptible to hypertension and atherosclerosis, which indicates that vascular amyloidosis (VA), hypertension, and atherosclerosis
However, there are only four kinds of amyloid proteins which are mainly associated with VA. In general, these four amyloid proteins TTR (Transthyretin), Apo1 (Apolipoprotein A-1), immunoglobin γ, and medin are susceptible to deposit, respectivelyat cerebral artery, coronary artery and aorta. If amyloid proteins deposit within the walls of the cerebral vasculature with subsequent aggressive vascular inflammation, it will lead to recurrent hemorrhagic strokes; If they deposit within the walls of
Growing evidence has indicated that MFG-E8 is a secreted inflammatory mediator that orchestrates diverse cellular interactions involved in the pathogenesis of various diseases, including vascular aging and amyloidosis. During aging, both MFG-E8transcription and translation increase within the arterial walls of various species. Many inflammatory molecules within the Ang II signal pathway are induced by MFG-E8. During amyloidosis, as the origin of amyloid protein, MFG-E8 cleaves into medin which
Endothelial integrity is important to vascular health, with endothelial cells (ECs) building the frontline cells of the arterial wall. It is suggested that the amyloidosis associated protein medin is toxic to aortic ECs in vitro and may underliethe pathogenesis of aortic aneurysm in vivo through a weakening of the aortic wall. In addition, the increased inflammatory load, such as elevated MFG-E8 in the old endothelia may damage endothelial mitochondrial DNA and interfere with the mitochondria
Link: https://doi.org/10.3389/fgene.2017.00126the amyloid beta seems to be part of the clotting process. A relatively new hypothesis is that the platelet derived amyloid beta peptides are carried to the brain and start the Alzheimer's Disease process of amyloid beta accumulating in the brain tissue.
I looked into the research on amyloid beta buildup in blood vessels and found that it is mainly produced and released from blood platelets (Inyushin, 2017). Once the platelets are activated inside the blood vessels they begin to aggregate and clot, and
Here are some references on the protective effects of Gilbert's Syndrome (a genetic condition affecting about 5-10 percent of Caucasians. Horsfall, 2013 Gilbert's Syndrome and the risk of death, a population based cohort study. Kundar, 2015 Bilirubin,platelet activation and heart disease: a missing link to caridovscular protection in Gilbert's Syndrome. Sung Young Kim, 2012 Physiological antioxidant network of he bilirubin system in aging and Age-related diseases. Most of these research or review
SOURCE: https://www.fightaging.org/archives/2017/11/considering-the-evidence-for-vascular-amyloidosis-as-a-cause-of-aging/
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