Targeting Hypercoagulation for Anti-Aging

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.

One of the most important of the proteins that promotes blood clotting is fibrinogen, and it markedly increases with age. Higher levels of fibrinogen are associated with heart disease and cancer.

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.

Why blood clots won’t break down

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?

Iron, for one.  Iron enhances the generation of fibrin, and makes it harder to break down.

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.

It’s even suggested that the presence of iron-induced fibrin clots may be the cause of the inflammation that raises fibrinogen, and could be very important for causing heart disease.

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.

Iron is well-known to be involved in Alzheimer’s disease, and the ability of iron to enhance clot formation may be one of the reasons.

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?

How to avoid the hypercoagulation of aging

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.

  1. Keep iron in the low normal range, via blood donation and/or iron chelators. Both can be useful, since blood donation targets total body iron, while iron chelators mop up any excess free iron.
  2. Magnesium can help dissolve fibrin-red cell aggregates. It’s therefore no surprise that magnesium reduces death rates in heart attack patients, and deficiency is associated with stroke.
  3. Polyphenols like EGCG (from green tea) and curcumin protect against hypercoagulation. No accident that they also chelate iron.
  4.  Aspirin enhances fibrinolysis. This may be one of its modes of action that protects against both heart attacks and cancer. Long-term aspirin use also results in lower levels of iron.


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.)

Even less discussed is the role of iron, whether it’s increasing fibrinogen, decreasing fibrinolysis, causing infections, cancer, or any number of other things, including aging itself.

PS: Read my book Dumping Iron.

PPS: Check out my Supplements Buying Guide for Men.


Leave a Comment:

Targeting Hypercoagulation for Anti-Aging | Technology and Longevity Feed says October 20, 2016

[…] Original Article: Targeting Hypercoagulation for Anti-Aging […]

BC says October 21, 2016

What, in your opinion, is the best or most effective iron chelator easily available?

    P. D. Mangan says October 22, 2016

    Either IP6 or curcumin.

      BC says October 23, 2016

      Thanks. I see that IP6 contains calcium. Is that enough of a dose to worry about?

        P. D. Mangan says October 23, 2016


Shaq says October 22, 2016

Saw your tweet; aspirin or ibuprofen as your preferred iron chelator?

And you are doing God’s work…..thank you.

    P. D. Mangan says October 23, 2016

    Hi Shaq – aspirin has far more data behind it. Ibuprofen could be better as far as risk, for example with bleeding. There was a report recently about ibuprofen being associated with heart failure, but those were huge doses, large amounts daily. So for now anyway, I’m going with aspirin just because it’s more of a known quantity. And thanks for saying that, a huge compliment.

      Shaq says October 23, 2016

      Looking forward to your next book:

      How to grow your portfolio when you’re 100 years old.

Do Bacteria Cause Hypercoagulation and Aging? - Rogue Health and Fitness says October 31, 2016

[…] recently wrote about hypercoagulation, which is the phenomenon of increased activation of blood clotting and decreased activation of clot […]

Joshua says November 18, 2016

Great article, PD. This is, again, a topic that I’ve never seen anything about….and I’ve read a LOT of health-related content on the ‘net.
I have to say, this blog delivers. I’ve been following it for maybe 2 years now (?). When I first found it, I thought it was very good — links to and brief analysis of studies that were quite relevant and interesting. Since then, it’s become far better. You’ve moved beyond the fairly well-known (among the aware, that is) health-related topics like resistance training and fasting and into stuff that seems pretty pioneering. Congratulations on your fantastic work and I look forward to reading more! (Though I suspect we should never discuss politics!)

    P. D. Mangan says November 18, 2016

    Thanks very much, Joshua. These are the kind of articles I most enjoy researching and writing. I hope it is pioneering. Are you aware of any of my articles at The Winnower?

      Joshua says November 21, 2016

      Why no, I wasn’t. I will take a look at those, thanks.

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