Coagulation (clotting) of the blood is an important process that keeps us from bleeding by stopping blood flow in a timely fashion. It’s intricately regulated by dozens of proteins, with positive and negative feedback loops. Hypercoagulation refers to the abnormally high tendency of the blood to clot, and there’s a marked association of hypercoagulation and aging. Here we’ll discuss targeting hypercoagulation for anti-aging.
Fibrinogen forms fibrin, which in turn forms a blood clot. Dissolution of fibrin is as important as its formation; clots that form too quickly or don’t dissolve soon enough can cause heart attacks, strokes, and deep vein thrombosis.
Why do fibrinogen levels rise with age? It may be due to inflammation, since fibrinogen is an acute phase reactant.
Noteworthy also is that fibrinolysis, the process of breaking down a blood clot, decreases with age. “[T]he increasing hypercoagulability observed with aging may account for the higher incidence of thrombotic cardiovascular disorders in the elderly”.
So, we have increased fibrinogen, possibly due to greater inflammation in aging, and decreased fibrinolysis, both of which tend toward the formation of blood clots, which increase the risk of heart attacks, cancer, and stroke, and probably lots of other diseases.
In fibrinolysis, the breaking down of blood clots, enzymes designed for that purpose act on fibrin. If something alters the molecular structure of fibrin, clot-dissolving enzymes can’t function as well, or even at all.
What could alter the fibrin structure?
Here, we show by means of electron microscopy that iron ions added to human blood dramatically enhances fibrin fibers formation with thrombin, and significantly delays fibrinolysis during spontaneous clotting of native blood. Iron ions caused the appearance dense matted fibrin deposits, similar, if not identical, to those observed in plasma of patients with stroke. These results may explain a known relationship between thrombotic diseases and the increased body concentrations of free iron and/or hemoglobin derivatives. We conclude that any action resulting in the inhibition of hemostatic abnormalities, as well as in the reduction of body free iron and scavenging of hydroxyl radicals (e.g., by polyphenols) can potentially prevent pathological reactions associated with consequences of stroke.
Iron, through its ability to generate hydroxyl radicals (OH¯), changes the structure of fibrinogen, and the fibrin formed by it, and makes it difficult to break down.
The mechanism of this phenomenon is very likely based on hydroxyl radical-induced modification of fibrinogen tertiary structure with the formation of insoluble aggregates resistant to enzymatic and chemical degradations.
Accumulating evidence within the last two decades indicates the association between cardiovascular disease (CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolytic enzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronary and cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron (FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that is remarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that the persistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. …We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated with CVD. The only way to prevent iron overload is by supplementation with iron chelating agents.
Iron appears to be the biggest culprit in the increased fibrinogen and decreased fibrinolysis seen in aging, and may therefore be largely responsible for increased rates of heart disease and cancer seen in older people.
Iron also increases with age, which gives us another piece of evidence in the chain: aging → more iron → greater tendency to clotting → heart disease, stroke, cancer.
Amyloid hypothesis of Alzheimer’s disease (AD) has recently been challenged by the increasing evidence for the role of vascular and hemostatic components that impair oxygen delivery to the brain. One such component is fibrin clots, which, when they become resistant to thrombolysis, can cause chronic inflammation. It is not known, however, why some cerebral thrombi are resistant to the fibrinolytic degradation, whereas fibrin clots formed at the site of vessel wall injuries are completely, although gradually, removed to ensure proper wound healing. This phenomenon can now be explained in terms of the iron-induced free radicals that generate fibrin-like polymers remarkably resistant to the proteolytic degradation…. In addition, iron-induced fibrin fibers can irreversibly trap red blood cells (RBCs) and in this way obstruct oxygen delivery to the brain and induce chronic hypoxia that may contribute to AD.
Iron: is there anything (bad) it can’t do?
Avoiding the hypercoagulation of aging would be a potent strategy for fighting aging and remaining free of the diseases of aging. There are a few ways to do this.
The hypercoagulation of aging represents an important target for any anti-aging and life-extension regimen. Even middle-aged men should pay attention to it, since they have a high rate of heart attacks — as well as high iron, which is why they have the high rate of heart attacks.
Unfortunately, no one is talking about this. While it’s well known that blood clots can precipitate heart attacks, the idea that hypercoagulation may be a (or the) root cause of heart disease is barely even considered. (Instead, we get all that cholesterol nonsense.)