I recently used The Clock Foundation to test for biological age https://clockfoundation.org/get-started/
Age-wise similar to TruDiagnostic. What was different was the report. This clock identified my vascular system as my high risk factor, indicating I had high levels of PAI-1 - an inflammation factor I had never heard of (plasminogen activator inhibitor).
Recommendations to lower this were:
-limit alcohol (I don’t drink)
-metformin (my fasting BS is already at 90)
-ACE inhibitor (my BP is 104/68 so this seems like a bad move)
-sleep (I get 7.5 hours)
-resvestoral (already take)
-exercise (could be improved but am quite fit)
-HRT (already do this)
Reading about PAI-1 it seems to be a metabolic disease. My fasting insulin is under 5 and BMI is only 18. Chat GPT says omega 3 and curcumin could help but I already take these.
I’ve worked on inflammation (cRP is 0.61 and ESR is 5) so not sure what to do to lower this blood factor.
Anyone ever hear of ways to improve PAI-1?
This is interesting @Paul. I wonder if a combination of serum insulin, fibrinogen, and 4-5 other metrics might be as or more predictive as the Pai-1 test. I put a general question to one of my AI systems and received this analysis. My other thought is that your metrics are enviably positive. I’m not sure why the recommendations of the aging test came out as they did.
PROMPT
Compare tests of serum pai-1 with serum fibrinogen for their sensitivity and specificity for identified negative and positive health outcomes.
PAI-1 (plasminogen activator inhibitor-1) and fibrinogen are both markers associated with coagulation and fibrinolysis, but they have distinct physiological roles and clinical implications. Comparing the sensitivity and specificity of tests for PAI-1 and fibrinogen with regard to negative and positive health outcomes provides insight into their use in identifying cardiovascular and metabolic risks.
1. Serum PAI-1
Role:
PAI-1 inhibits tissue plasminogen activator (tPA) and urokinase, both of which are involved in breaking down fibrin clots. Elevated PAI-1 levels can impair fibrinolysis, promoting thrombosis.
Sensitivity and Specificity:
-
Sensitivity:
- PAI-1 is sensitive to conditions of metabolic syndrome, obesity, and type 2 diabetes. Elevated PAI-1 levels correlate with increased risk of thrombotic events such as myocardial infarction, stroke, and venous thrombosis.
- It is sensitive to early inflammatory and metabolic dysregulation, particularly in insulin resistance.
- It is also sensitive to circadian variations, diet, physical activity, and stress.
-
Specificity:
- While PAI-1 levels are highly specific to prothrombotic states, its levels can be influenced by factors like obesity, insulin resistance, and chronic inflammation. This broad association makes it less specific to a single condition, as elevated levels can result from multiple disorders, including metabolic syndrome and cardiovascular diseases.
Clinical Utility:
- Positive health outcomes: Low levels of PAI-1 are generally considered favorable, as this suggests a lower risk of thrombosis and better fibrinolytic balance.
- Negative health outcomes: Elevated PAI-1 levels are associated with poor health outcomes such as coronary artery disease, atherosclerosis, and insulin resistance, with a strong link to cardiovascular morbidity and mortality.
2. Serum Fibrinogen
Role:
Fibrinogen is a soluble plasma glycoprotein that is converted by thrombin into fibrin during blood clot formation. Fibrinogen is also an acute-phase reactant, meaning its levels rise in response to inflammation.
Sensitivity and Specificity:
-
Sensitivity:
- Fibrinogen levels increase in a wide array of inflammatory conditions, making it highly sensitive to states of systemic inflammation, infection, and tissue injury.
- It is a sensitive marker for cardiovascular risk, as elevated levels are correlated with increased incidence of stroke, myocardial infarction, and peripheral artery disease.
- It is sensitive to environmental and lifestyle factors such as smoking, obesity, and diet, which can cause transient or chronic elevations.
-
Specificity:
- Fibrinogen has lower specificity compared to PAI-1 because elevated levels can be observed in almost any inflammatory condition, not just cardiovascular events. This includes infection, trauma, autoimmune diseases, and even cancer.
- Its broad role as an acute-phase reactant reduces its specificity for cardiovascular events alone, although it remains a valuable component of cardiovascular risk assessment.
Clinical Utility:
- Positive health outcomes: Low or normal fibrinogen levels are generally associated with a reduced risk of thrombosis and cardiovascular disease. They are indicative of lower inflammation and a more stable vascular state.
- Negative health outcomes: High fibrinogen levels are associated with a range of poor health outcomes, including cardiovascular diseases (stroke, myocardial infarction), systemic inflammatory states, and increased mortality in conditions like sepsis or chronic inflammatory diseases.
Comparison of Sensitivity and Specificity
| Marker | Sensitivity | Specificity |
|---|---|---|
| PAI-1 | Sensitive to metabolic disorders, cardiovascular risk, obesity, insulin resistance, and thrombotic conditions. | Less specific due to wide-ranging associations with metabolic and cardiovascular states, but more tied to thrombotic risks. |
| Fibrinogen | Highly sensitive to inflammation, infection, cardiovascular risk, and lifestyle factors (smoking, diet). | Low specificity due to its role as an acute-phase reactant in many inflammatory and non-inflammatory conditions. |
Summary of Findings:
- PAI-1 tests are more specific to conditions with prothrombotic risks and metabolic disorders like type 2 diabetes and cardiovascular diseases. However, because PAI-1 is influenced by a variety of metabolic and inflammatory states, it may lack absolute specificity.
- Fibrinogen tests are highly sensitive to inflammation and cardiovascular risk, but their lack of specificity due to involvement in any inflammatory process makes them less diagnostic for specific cardiovascular or thrombotic conditions.
Both markers are valuable in risk stratification for cardiovascular events, but PAI-1 may be more specific for assessing prothrombotic risk in metabolic disorders, while fibrinogen serves as a broader marker for systemic inflammation and vascular risk.
Another piece of information.
https://www.ahajournals.org/doi/10.1161/circulationaha.106.616177
Thanks, both articles point to metabolic disorders as a cause which does not seem applicable in my case.
I did come across some papers suggesting natto might help
NK enhanced fibrinolysis through cleavage and inactivation of PAI-1. 4 In
this study, NK was shown to cleave active recombinant prokar-
yotic PAI-1 into low-molecular-weight fragments as well as
enhance tissue-type plasminogen activator–induced fibrin clot
lysis. The enhanced fibrinolytic activity observed in the absence
of PAI-1 appeared to be induced through direct fibrin dissolution by NK.4
The Clock Foundation will do a follow-up call with you right? Did they have any additional info to provide given you are doing all the interventions already?
One conclusion in this review is that the availability of natto via oral ingestion has not bee adequately studies according to these excerpts [editing mine].
One key question that has not been adequately addressed is the mechanism by which NK is absorbed into the bloodstream after oral administration. There is no current convincing data available to demonstrate the bioavailability and metabolism of NK administered as an oral dose . . . Recent pilot studies on the pharmacokinetics of NK have not provided an answer to the question of how NK is absorbed into the body. . . Ero et al. claimed that NK was measured directly in their study with a peak concentration at 13.3 hours after oral administration, whereas the thrombolytic activity of NK, measured in another study, was shown to peak 2 to 4 hours after oral dosing . . . These data imply that measurements of NK in the published studies may not be those of the intact NK molecule . . . several groups have pointed out that the molecular size of NK is considered to be generally too large for oral absorption through the GI tract . . . It is [also] recognised that NK may be susceptible to chemical oxidation and subsequent inactivation, or denaturation, in the GI tract.
yes, I have a call scheduled next week