Longevity Biomarkers 101: What to Test and Why

No aspect of health is one-size-fits-all—and longevity is no exception. Testing longevity-related biomarkers can provide valuable insights into how healthfully you are aging, as well as help create a supplement plan personalized to you and your unique health needs. But typically, simply going to your regular primary care doctor and getting routine labs won’t cut it—there are many biomarkers specific to healthspan and lifespan that you may need to specifically request or get tested at specialized laboratories or clinics. 

However, it’s important to keep in mind that the research on some longevity biomarkers is developing and ongoing, meaning that more studies are needed to verify their accuracy. Plus, while many biomarkers can certainly provide helpful information about your personalized health status, biomarkers alone cannot predict your lifespan, as hundreds of factors play a role in your overall aging process. That said, tracking these six biomarkers (or categories of biomarkers) can help you take proactive charge of your health, make lifestyle changes if need be, and allow for earlier detection and treatment of chronic health conditions.

Telomere Length

Telomeres are the endcaps on the tips of chromosomes, protecting our cells and DNA. Similar to the plastic casing securing the tip of a shoelace from fraying, telomeres protect the chromosome from damage, dysfunction, and premature aging. 

They shorten with each cell division to preserve critical genetic information—but when a cell reaches the end of its telomere, it can no longer replicate and loses function. When a cell’s telomere gets too whittled down, the cell can no longer replicate and is considered senescent. Cellular senescence is another marker of aging, which occurs when cells stop dividing, lose function, and trigger a cascade of inflammatory compounds that accelerate aging.

Telomere length is considered a proxy for biological aging, as shorter telomere length is linked to shortened lifespans and earlier disease onset. Multiple methods have been developed to assess telomere length, and many biological age tests utilize telomeres to determine your internal age.

Epigenetics and DNA Methylation

As opposed to genetics, which is simply the set of genes you have, epigenetics tells you which genes are active or turned “on” or “off.” Epigenetic age is measured by chemical changes or “tags” on DNA. This includes DNA methylation—the addition of a methyl group to DNA—which doesn’t change the DNA sequence itself but, rather, leads to alterations in gene activity. 

These chemical tags, which arise from lifestyle, diet, and environmental conditions, occur long before symptoms of diseases appear, making epigenetics a valuable way to predict age-related disorders. As aging increases the amount of methylated DNA, epigenetic “clocks” are often considered an excellent representation of biological age—how fast our cells, organs, and tissues are aging compared to our chronological, or birthday-based, age. 

Methods to assess biological age include using saliva or blood samples to track epigenetic changes. Commonly used epigenetic clocks include the Horvath clock or the Hannum clock, which estimate biological age based on DNA methylation patterns at specific regions. 

Inflammatory Markers

Chronic inflammatory states can lead to accelerated aging, as these pathways cause oxidative stress and damage to cells, proteins, and DNA. Elevated levels of inflammatory markers have been associated with a higher risk of mortality in older adults. Studies have shown that people with higher levels of inflammatory markers are more likely to have shorter lifespans than those with lower levels.

Some inflammatory markers to assess include:

• Hs-CRP (high-sensitivity C-reactive protein): While hs-CRP itself does not predict longevity, higher levels of it are associated with low-grade inflammatory states that increase the risk of various age-related diseases. Higher CRP levels are particularly linked to worse cardiovascular health, which is a significant factor influencing longevity.
• IL-6 (interleukin-6): IL-6 is a pro-inflammatory cytokine (signaling molecule) produced by immune cells in response to infections, tissue damage, or inflammatory states. Higher IL-6 levels increase oxidative stress and have been linked to cardiovascular, cognitive, and joint conditions. Some studies suggest that lower levels of IL-6 are associated with better health outcomes and increased longevity in older adults. 
• TNF-alpha: As another pro-inflammatory cytokine involved in the immune response, lower levels of TNF-alpha may be linked to improved health outcomes in older adults. 

Cardiometabolic Markers

Biomarkers related to cardiovascular or metabolic health—like blood glucose, insulin sensitivity, and lipid levels—can give us insights into health and aging, as cardiometabolic conditions are strongly linked to mortality. 

Some cardiovascular or metabolic biomarkers to measure include:

• Fasting Blood Glucose: High fasting blood glucose is a hallmark of metabolic disorders, which can lead to cardiovascular, nerve, kidney, and vision problems, as well as increased mortality. Keeping a close eye on fasting blood sugar levels is critical for maintaining health and preventing metabolic disorders from arising.
• Insulin Sensitivity: Similar to blood sugar, insulin sensitivity is also a strong biomarker for health and longevity. The opposite state, insulin resistance, is a condition where cells become less responsive to insulin and is associated with metabolic disorders. Research shows that longer-lived adults have better and more sensitive insulin signaling. 
• ApoB: Apolipoprotein B (apoB) is a protein involved in fat metabolism that is a crucial component of lipoproteins like LDL and VLDL. While apoB itself is not a direct marker of longevity, it is indirectly linked to health outcomes that can affect lifespan because higher levels of apoB are linked to higher LDL cholesterol and cardiovascular conditions. 

Oxidative Stress

Oxidative stress—the accumulation of harmful and damaging compounds called free radicals or reactive oxygen species (ROS) with inadequate antioxidants to neutralize them—is linked to accelerated aging and chronic disease development. 

Several biomarkers of oxidative stress measure either the level of oxidative damage or how well the body can cope with and neutralize the reactive molecules, including:

• MDA (malondialdehyde): A measure of lipid (fat) peroxidation. Fats in cell membranes are particularly vulnerable to free radical oxidation and create lipid peroxides when attacked and damaged.
• Superoxide dismutase (SOD), catalase, or glutathione peroxidase: Enzymes that are part of the body's antioxidant defense system. Lower levels of these enzymes indicate a lesser ability to neutralize free radicals.
• 8-OHdG: A marker of DNA damage, as oxidative stress commonly damages DNA.

Sex Hormones

The hormones estrogen, testosterone, and DHEA have roles that go far beyond sex and reproduction, with functions including cardiovascular, cognitive, muscular, bone, and mental health, all of which can impact longevity.

In women, starting menopause earlier leads to lower lifetime estrogen levels and is linked to reduced lifespan. In a study of over 1,200 women, those who experienced premature menopause (age 39 or younger) had a 46% increased risk of mortality from any cause compared to women with average-aged menopause. Testosterone and DHEA also decrease with age in women, leading to changes in libido, energy levels, and body composition, including lower muscle mass, which is associated with increased mortality. 

In men, higher testosterone levels increase skeletal muscle mass, grip strength, walking speed, and physical performance. Testosterone levels also impact longevity, as seen in this study of over 10,200 men that found those with the lowest testosterone to have the highest rates of all-cause mortality, especially after age 60.

Men in their 40s and beyond also experience decreases in DHEA, a hormone produced by the adrenal glands. DHEA is a precursor for other hormones (including estrogen and testosterone) and aids in muscle maintenance, cognitive function, mood, and antioxidant defense. 

Key Takeaways:

Longevity and lifespan are highly complex, influenced by hundreds of factors, including genetics, diet and lifestyle choices, exercise, access to healthcare, environmental factors, and overall health status. However, measuring and tracking longevity-related biomarkers can be a great way to become proactive about your future health, identify risk factors or early detection of disorders that impact mortality, and personalize your approach to longevity. 

References:

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