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 senescent
cells 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
of this combines to degrade the feedback system controlling pressure in the cardiovascular system, and blood pressure rises as a result. In turn, the heart remodels itself, becoming larger and weaker.
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 become
irritated 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
blood vessel wall - the condition known as atherosclerosis. The combination of weakened blood vessels and rising blood pressure is ultimately fatal: a large vessel ruptures, producing a heart attack or stroke.
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
circulatory systems and heart tissue clogged with the stuff. So where does amyloid fit in to vascular aging? Is it mixed in with cross-links and senescent cells from the start, causing stiffening and failure of vascular contraction? Or does it only arise
in significant amounts later, enabled by earlier forms of damage? This open access paper looks over some of what is known on this topic.
Quote:
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
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
fibrils. About 30 proteins are known to form pathogenic amyloid or amyloid-like fibrillary networks in a wide range of human tissues which are associated with diseases having high morbidity and mortality rates.
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, respectively at
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 the
coronary artery, they will lead to angina pectoris, even ischemic cardiomyopathy; If they deposit within the wall of aorta, they will lead to hypertension, atherosclerosis, and even dissecting aneurysm eventually.
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-E8
transcription 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
increases the stiffness of vascular wall through the binding to tropoelastin. These medin amyloids have been observed within arterial walls, including that of both aorta and temporal artery.
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 underlie the
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 life
cycle via enhanced reactive oxygen species generation, which consequently initiates and promotes EC senescence and apoptosis. These cellular events and micro-environments lead to endothelia dysfunction which renders the arterial wall a fertile soil in
which amyloidosis and atherosclerosis may flourish. Interestingly, endothelial dysfunction also occurs with aging even in healthy adults, and collectively, endothelial dysfunction can be viewed as a prelude for arterial disease.
Link:
https://doi.org/10.3389/fgene.2017.00126
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
the 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.
One thing that may slow this process is if you have less platelets. I have Gilbert's Syndrome, which has 2 to 3X higher levels (mine is 2.3) of the very strong antioxidant bilirubin than normal people, that protects the lining of the blood vessels from
oxidative stress and abnormal clotting, etc. Also, Gilbert's Syndrome results in about a 40% reduction in platelet count (mine is 103K), which would reduce amyloid production and risk of clots, heart attacks, strokes, and probably AD as well. Gilbert's
Syndrome has an all cause mortality risk of 0.5. Only problem is, Gilbert's Syndrome is only carried by 5-10% of Caucasians. But in the future, with CRISPR technology, it may be possible to transplant the GS SNP's to your genome.
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
papers deal mainly with bilirubin as a strong antioxidant that is very protective of atherosclerosis, but as I have noted in my earlier comment above, GS has about a 40% reduction in platelet count, which many disease protective aspects as well for
protection against clotting, heart attacks, strokes and AD as well.
SOURCE:
https://www.fightaging.org/archives/2017/11/considering-the-evidence-for-vascular-amyloidosis-as-a-cause-of-aging/
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