Understanding Healthspan vs. Lifespan: Best Longevity Blood Tests

In the journey of human health, two terms often come into focus: healthspan and lifespan. Lifespan refers to how long you live, while healthspan is about the quality of those years – specifically, the period during which you are free from serious diseases and enjoy a good quality of life. The distinction is crucial: living longer doesn’t always mean living better. This is where the concept of healthspan gains importance.

In some cases, you can feel the differences in your health, but many physiologic changes will only show up in measurements. This is where health wearables and lab tests are crucial.

Aside from helping doctors diagnose diseases, certain lab tests can provide a wealth of information about your health by:

• Predicting the likelihood of future diseases and health complications
• Signaling the onset of diseases
• Tracking the progress of a condition
• Predicting your overall wellness and risk of death
• Gauging the effectiveness of lifestyle changes and treatments. 

Therefore, getting the right blood test and interpretations can provide useful insights to extend both your lifespan and healthspan, even if all your numbers come back normal. Health and performance optimization requires that your lab numbers be within the optimal range, not just normal range. 

Currently, there is no official scientific consensus on the best way to derive optimal lab ranges–some practitioners correlate it with the best clinical outcomes, while others correlate it with the lowest all-cause mortality.

Therefore, interpreting lab tests for healthspan can be very different from how most conventional doctors do it to diagnose diseases. So, you may wish to work with an integrative or anti-aging doctor to test and follow these labs.

Each biomarker discussed below measures a slightly different perspective of health and, therefore, can give different actionable anti-aging insights. 

High-sensitivity C-reactive protein (hs-CRP)

C-reactive protein is a protein made in the liver that goes up when there’s inflammation in your body. Hs-CRP measures the level of C-reactive protein in your blood. A high-sensitivity CRP test (hs-CRP) can pinpoint smaller increases in CRP to track the progress of inflammatory diseases. 

Inflammation can contribute to many diseases, and it tends to go up with age with a phenomenon called inflamm-aging. Also, inflammation can worsen physical pain, affecting your mobility and functionality. So, how well you manage your inflammation levels can be a strong measure of healthspan and all-cause mortality.  

Elevated hs-CRP (1.7 mg/L or higher) is associated with increased all-cause mortality. A cohort study of 3,119 participants demonstrated that high hs-CRP levels are associated with a 77% greater chance of death (Hazard Ratio (HR) = 1.77). Importantly, elevated hs-CRP lasting over 7 years correlates with a 150% greater chance of death (HR = 2.5). 

The good news is that if you know your hs-CRP is high, lifestyle optimization including the following can be very beneficial:

• Nutrition 
• Exercise
• Stress management
• Gut health and gut flora optimization  
• Weight loss
• Smoking cessation
• Hormesis, such as heat or cold exposure, and fasting

HbA1c

HbA1c gives you the average blood sugar level over the past 3 months. It’s used to diagnose and monitor diabetes. It can also give you insight into your blood sugar control and how your blood sugar affects your tissue aging. 

Elevated HbA1c levels are strongly linked to an increased risk of diabetes-related complications, which can significantly affect both healthspan and lifespan. However, HbA1c has its limitations. It may not be as accurate in individuals with conditions that affect hemoglobin’s lifespan in your blood, such as:

• Certain hemoglobin variants
• Recent blood transfusions 
• Anemia 
• Kidney disease. 

Furthermore, it doesn’t reflect daily blood sugar fluctuations, which can affect your brain functions and overall well-being.

A meta-analysis of 7 observational studies comprising 147,424 participants observed a J-shaped, non-linear trend between HbA1c levels and all-cause mortality. There was a 4% overall increase in all-cause mortality risk for every 1% increase in A1c levels over 7.5%.

Insulin/HOMA-IR (Homeostatic Model Assessment of Insulin Resistance)

Insulin/HOMA-IR is a test used to estimate the level of insulin resistance in the body. Insulin resistance is a condition where cells in muscles, fat, and the liver don’t respond well to insulin and can’t easily take up glucose from the blood. As a result, the pancreas makes more insulin to help glucose enter the cells. This can also cause elevated blood sugar, increasing overall oxidative stress and tissue glycation. 

HOMA-IR calculates insulin resistance by using a formula that incorporates fasting blood glucose and fasting insulin levels.

High HOMA-IR scores indicate higher levels of insulin resistance, which can signify a higher risk for blood sugar-related conditions, potentially impacting both healthspan and lifespan. Even without diabetes and metabolic syndrome, poor blood sugar control also correlates with cognitive decline, vision problems, and skin aging. Therefore, keeping your blood sugar and insulin optimized is crucial for your healthspan. 

A retrospective analysis of 5,511 non-diabetic participants in a nutrition study found that HOMA-IR was significantly correlated to all-cause mortality. There was a 64% increased risk of death in high (> 2.8) HOMA-IR levels (HR = 1.64), but only in participants with a BMI less than 25.2. HOMA-IR levels above healthy (>1.4) were significantly associated with cardiovascular mortality, but not cancer mortality. 

The test isn’t perfect—results can be skewed by certain conditions or medications. But if you’re insulin resistant, working on diet and exercise can lower your risk for diabetes and its complications.

Knowing your HbA1c and HOMA-IR levels can guide important lifestyle changes and treatment adjustments, such as:

• Diet modifications to stabilize your blood sugar
• Increasing physical activity
• Working with your doctor to adjust medications that affect your blood sugar control, if applicable
• Monitoring your blood sugar responses to food and life events with tools like continuous glucose monitoring

Proactive steps can help improve blood sugar control, reduce the risk of related health issues, and potentially enhance the length and quality of life.

Lp(a)

Lipoprotein A [Lp(a)] is a low-density particle made of protein and fats that travels through your blood and carries cholesterol, fats, and proteins. High levels can mean a greater risk of cardiovascular diseases.

Unlike other cholesterol measures, you mostly inherit your Lp(a) levels from your parents. A meta-analysis of 75 studies found that each 50 mg/dL increase in Lp(a) levels increased death from cardiovascular incidents by 30%. The risk of all-cause mortality increased by 9% in the general population and 18% in people who already have cardiovascular diseases in those with high Lp(a) levels (50 mg/dL or greater). 

Another large British study involving 139,362 participants found that high genetic risk scores were inversely associated with parental lifespan and healthspan. 

It’s not entirely clear how Lp(a) affects healthspan or lifespan, but it’s one piece of the puzzle. Lp(a) may explain why some very fit and healthy people develop cardiovascular issues or even drop dead, especially those of European descent. Therefore, testing Lp(a) and being proactive if it’s high can save your life. Doctors may treat it with high-dose niacin or statin, but some lifestyle factors like exercise and weight loss may also be beneficial.

ApoB

Apolipoprotein B (ApoB) is a protein crucial for the metabolism of lipids (fats) and is a primary component of low-density lipoprotein (LDL), often referred to as “bad cholesterol.” Each LDL particle contains one ApoB molecule, so measuring ApoB levels provides an estimate of the number of LDL particles in the bloodstream. 

High ApoB levels are closely linked to an increased risk of cardiovascular diseases, which are major determinants of lifespan and quality of life. ApoB can be a more precise indicator of heart disease risk than traditional cholesterol tests.

A retrospective analysis of 10,375 nutritional study participants discovered a U-shaped relationship between ApoB levels and all-cause mortality, with the lowest risk occurring at 108mg/dL. You don’t want too high or too low ApoB. ApoB levels had a linear relationship with cardiovascular mortality – a 25% increase in ApoB levels correlated with a 13% increase in mortality (HR = 1.13). 

However, ApoB can also be influenced by genetics, diet, and other lifestyle factors.

ApoB levels don’t reflect the cholesterol content within LDL particles or their size, both of which can affect disease risk.

Similar to Lp(a), high ApoB levels can prompt you to make changes such as diet, lifestyle, weight management, and, if necessary, medications.

DHEA-S

Dehydroepiandrosterone Sulfate (DHEA-S) is a steroid hormone produced by your adrenal glands. It’s a precursor to sex hormones like testosterone and estrogen. DHEA-S in the body peaks in early adulthood and then gradually declines with age, which is why it is sometimes viewed as a marker of aging.

The measurement of DHEA-S levels is often used to evaluate adrenal gland function and to diagnose certain conditions related to hormone imbalance. Healthy-high levels of DHEA-S are associated with increased longevity and reduced risk for certain age-related diseases, such as osteoporosis and cardiovascular diseases.

A meta-analysis of six longitudinal studies with a total of 6,744 elderly participants analyzed the association between DHEA-S levels and all-cause and cardiovascular mortality. Low DHEA-S levels (25 µg/dL or below) were associated with a 146% and 149% increase in all-cause and cardiovascular mortality, respectively (RR = 1.46, RR = 1.49). Gender-specific analysis showed that increased risk of all-cause mortality existed only in elderly men, not women. 

The link between DHEA-S levels and healthspan is still not well-established. Although DHEA-S can predict aging in animals maintained on a standard diet, dietary manipulations may affect liver enzymes involved in the metabolism of steroid hormones.

PULS (PROTEIN UNSTABLE LESION SIGNATURE)

PULS is a blood test that measures the body’s immune response to arterial injury. PULS measures injuries that lead to the formation of heart lesions which can cause heart attacks. 

This test measures multiple proteins produced by the body in response to damage to the inner lining of blood vessels, including those involved in inflammation, stress response, and vascular injury. These proteins include:

• hs-CRP
• Fibrinogen, a protein involved in blood clot formation. 
• Hemoglobin A1c
• NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide): Elevated levels indicate heart failure and are associated with increased cardiovascular risk. 
• Homocysteine, an amino acid linked to a higher risk of coronary artery disease.
• Omega-3 Index, a measure of the amount of omega-3 fatty acids, which are linked to cardiovascular health.
• Lipoprotein(a)
• IL-16 (Interleukin-16), a cytokine that plays a role in inflammatory responses.
• sFas (Soluble Fas), a marker involved in the regulation of cell death (apoptosis).
• Placental Growth Factor, involved in angiogenesis (the formation of new blood vessels).

PULS test can predict acute coronary syndromes, such as heart attacks, within a five-year period. By identifying individuals at higher risk, the test provides early intervention opportunities, potentially extending healthspan by addressing and mitigating cardiovascular disease risks before they lead to a cardiac event. Interventions can include:

• Diet and exercise changes
• Frequent monitoring
• Medication to address cholesterol or blood pressure

While it offers valuable insights, it should not be the sole basis for assessing cardiac health or the risk of heart disease. It’s one element in a comprehensive assessment that should include traditional risk factors like blood pressure, age, cholesterol levels, family history, and lifestyle factors.

GGT

Gamma-Glutamyl Transferase (GGT) is an enzyme that plays a key role in the metabolism of glutathione, a major antioxidant in the body. GGT is primarily found in the liver, and its levels are often measured to assess liver health. 

Elevated GGT levels can indicate liver damage or inflammation, which may be due to:

• Alcohol consumption
• Nonalcoholic fatty liver disease
• Hepatitis
• Bile duct problems

GGT can be especially valuable as a predictor of healthspan and lifespan since it predicts your overall cellular antioxidant inadequacy and toxic load. In a 2006 NHANES study that examined blood lead and urinary cadmium, higher GGT was associated with lower blood carotenoids and antioxidant vitamins [R21]. 

It’s also an early predictive marker for many health conditions such as atherosclerosis, heart failure, gestational diabetes, infectious diseases, and more. 

A Korean cohort study analyzed the relationship between GGT and all-cause mortality in over 9.6 million people without viral hepatitis or cirrhosis. High GGT levels (44 IU/L or greater in men, 21 IU/L or greater in women) were associated with a 33% increase in all-cause mortality (HR = 1.33), a 29% increase in cardiovascular mortality (HR = 1.29), a 38% increase in cancer (HR = 1.38), a 39% increase in respiratory disease mortality (HR = 1.39), and greater than a 500% increase in liver disease mortality (HR = 6.73). 

Elevated GGT levels can prompt further investigation to identify and address underlying causes. It can lead to lifestyle changes such as:

• Reducing alcohol consumption
• Improving diet to include more food-based antioxidants
• Increasing physical activity
• Managing weight
• Consulting your physician to treat any liver conditions, if applicable

Biological or Cellular Age Estimation Formulas

Could an active, happy, and fully independent 100-year-old in Okinawa be biologically younger than a bed-ridden 65-year old in the United States? 

Here, the Okinawan could be biologically younger than the American, even though the former is chronologically 35 years older. This is why our biological age can be different, and it’s now (imperfectly) measurable.

Anti-aging researchers have devised several measurements to estimate your cellular or biological age using cellular and blood tests. These tests are not diagnostic but their results tend to inversely correlate with the risk and severity of diseases of aging, such as diabetes, obesity, heart diseases, and inflammatory conditions. 

None of these tests is perfect, but they can often provide useful and actionable insights to improve your healthspan. 

Each biological age test offers a unique window into each intricate process or contributor to aging. These tools not only enhance our understanding of the aging process but also open avenues for targeted interventions to improve healthspan and potentially alter the trajectory of aging itself. 

Age Estimation Formulas: An Insight into Biological Age

Telomere Length

This method assesses biological age by measuring the length of telomeres, the protective caps at the ends of chromosomes. The more time your cells have divided, the shorter your telomeres get and the less your tissues are able to regenerate. Therefore, shorter telomeres are associated with aging and age-related diseases.

• Strengths: Telomere length is a direct biological marker and is relatively easy to measure with a blood test.
• Drawbacks: Telomere length varies significantly among individuals and can be influenced by:
  • Genetic factors
  • Lifestyle
  • Environmental exposure

Despite high correlation, It may not always reflect the true biological age or the health status of an individual.

Unlike other age estimation methods, telomere length provides a more genetic and cellular aging perspective, focusing on chromosomal changes.

Horvath’s Clock

Horvath’s clock was developed by Dr. Steve Horvath in 2013. This method uses DNA methylation levels to predict biological age. The clock analyzes the methylation status of 353 specific markers in the DNA. 

DNA methylation involves the addition of a methyl group (one carbon atom and three hydrogen atoms) to the DNA molecule. This process is a type of epigenetic modification, meaning it affects cellular production (gene expression) without altering the underlying DNA sequence.

DNA methylation plays a crucial role in controlling gene readouts. As we age, the pattern of DNA methylation in our cells changes, which can affect the expression of genes involved in various biological processes and diseases.

• Strengths: Horvath’s Clock is highly accurate and comprehensive, considering a wide array of genes. It has been validated across various tissues and cells.
• Drawbacks: The process requires sophisticated laboratory techniques and analysis. It might not fully account for lifestyle and environmental factors affecting aging.

Horvath’s clock offers a more detailed and genetic-based estimation of biological age compared to simpler biomarker-based formulas.

Biomarker Based Formulas

In 2018, a cohort study developed a new aging measure, coined ‘Phenotypic age’, based on various biomarkers. The formula is as follows:

To estimate biological age, this method uses a combination of various blood tests readily accessible through a basic metabolic panel (BMP) and a complete blood count (CBC). These are two very common and affordable lab tests. Each biomarker contributes data related to specific aspects of health, such as inflammation, glucose metabolism, or liver function.

Other formulas also exist, including:

• Klemera and Doubal’s method (KDM): The specific biomarkers can vary but often include factors like blood pressure, cholesterol levels, and other blood-based measurements.
• Strengths: Biomarker-based formulas can provide a broader picture of physiological aging and health risks. They are practical as many of these biomarkers are routinely measured in standard blood tests.
• Drawbacks: The accuracy can vary depending on which biomarkers are included. They might not capture all aspects of aging, such as genetic factors or cellular changes.

Each of these age estimators provides unique insights into biological aging, with their respective strengths and limitations. 

Telomere Length offers a cellular aging perspective, Horvath’s Clock delves deep into the epigenetic aspects, and biomarker-based formulas provide a practical approach to assessing physiological aging. The choice of method depends on the specific aspects of aging and healthspan one wishes to understand and the resources available for analysis.

Conclusion

These lab tests and other health measurements, when done proactively, can help estimate your healthspan and provide actionable insights to optimize your health. You can also incorporate them to estimate your biological age. By working with an anti-aging medicine physician, you can:

• Regularly test and track the relevant lab tests
• Learn about the best ways to maximize your healthspan based on objective test results
• Catch diseases early or before they occur
• Get objective feedback on your anti-aging diet, exercise, sleep, supplements, biohacks, and other lifestyle changes