The Basics of Epigenetic Age Testing and How to Use It to Support Longevity

As opposed to the somewhat arbitrary chronological age that measures the number of years you’ve spent on the earth, biological age assesses internal aging. Essentially, biological age is a marker of the damage and dysfunction to cellular and molecular markers that you’ve built up over the years, representing how slowly—or quickly—your body is aging on the inside.

Biological age tests—which include epigenetic clocks and DNA methylation—can serve as important biomarkers of longevity at a molecular level. With this knowledge, people can begin to make informed and proactive changes to their health status before it’s too late.

What Are Biological Age Tests?

Biological age tests commonly combine several biomarkers, including telomere length (or attrition), DNA methylation, and “omics”-based markers, including proteomics, metabolomics, or transcriptomics, to estimate how well the body is aging relative to its chronological age.

Briefly, here are some of the main ways to measure biological age (in addition to epigenetics and DNA methylation, which we’ll dive deeper into in the next section):

• Telomere length: Telomeres are the endcaps on the tips of chromosomes, protecting them from damage and dysfunction. Telomeres shorten with each cell division in order to preserve critical genetic information—but when a cell reaches the end of its telomere, it can no longer replicate and loses function. Shorter telomeres are linked to shorter lifespans and an increased risk of disease development.

• Transcriptomics: Changes to the transcriptome, or the complete set of messenger RNA molecules that synthesize proteins from genetic material, are linked to biological aging. A loss of transcriptional regulation occurs with age, changing the blueprint for protein synthesis.

• Metabolomics: This is the study of the metabolome—a group of small molecules involved with metabolism called metabolites. Age-related changes to the metabolome can include reductions in the vital coenzyme NAD+ and increases in inflammatory metabolites. 

• Proteomics: Proteomics looks at the proteome—the entire compilation of proteins in the body. With age, the proper synthesis, folding, and regulation of proteins deteriorates. 

How Epigenetic Age Testing Works

While some biological age tests utilize several different longevity markers, epigenetic age tests solely use epigenetic patterns. Epigenetic age is measured by chemical changes or “tags” on DNA. This includes DNA methylation—the addition of a methyl group to DNA.

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. Although epigenetic changes are heritable and can be passed along from parent to child, these modifications do not change the actual DNA sequence. Instead, epigenetic changes—like DNA methylation—affect how our cells read the genes. 

As aging increases the amount of methylated DNA, epigenetic “clocks” are often considered an excellent representation of biological age. However, DNA methylation in itself is neither good nor bad—both over- and under-methylation can be harmful. Rather, methylation can result in specific genes being turned on or off. 

Some genes we would prefer to stay “on,” like those that allow for autophagy or breaking down toxins, while others, like those promoting inflammatory pathways, would be best turned “off.” However, with age or unhealthy lifestyles, our genes often do the opposite of what we would want.

How Is Epigenetic Age Measured?

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. 

These specific areas are typically small DNA regions called CpG islands. These islands tend to be clustered around genes and can change genetic activity—not changing the genes themselves, but how they act or function. Reversing DNA methylation at CpG sites is considered a potential anti-aging strategy for restoring gene activity and thereby improving physiological function. 

Although there are 20 million or so methylation sites on the human genome, just a few thousand of them are highly correlated with aging, with about 60% of the sites losing methylation and 40% becoming over-methylated with age. Methylation changes like these have been implicated in damage to DNA signaling, repair, and replication—but the good news is that it’s considered a reversible epigenetic biomarker. 

While blood is the most commonly used substance for clinical analysis, saliva is another option—plus, saliva samples are easier to collect, can be done at home, and are much less invasive than blood samples. 

However, you may wonder if saliva can gain the same epigenetic data as blood. Research published in the journal Frontiers in Aging suggests that, yes, saliva samples produce similar results. Saliva contains high-quality DNA and a wide range of clinically relevant molecules, including inflammatory markers, microRNA, and RNA antibodies. Saliva is also rich in white blood cells and buccal cells—cheek cells commonly swabbed in DNA and PCR tests. 

You can test your own epigenetic age using the TruMe test kit. These tests are ideally repeated every 6 months or so to assess if the lifestyle changes you make are, in fact, making an impact on your biological age.

How to Use Epigenetic Age Testing to Support Longevity

While knowing your epigenetic or biological age certainly sounds beneficial, you may wonder what exactly you’re supposed to do with that information. To put it simply, the more we know about defining and quantifying aging on a cellular level, the more doors open to prevent, treat, or reverse it. 

Although “reversing aging” sounds like something out of a sci-fi novel, recent research has suggested that certain dietary and supplement protocols can actually turn back time—at least in the epigenetic sense. While you will never be able to claim a different year on your birth certificate, there are many things you can do to slow down or reverse biological aging on the inside. 

As detailed in this article about reversing biological age, some nutrients, supplements, and lifestyle choices to consider to target DNA methylation or other hallmarks of aging include:

• Folate
• Vitamin B12
• Coenzyme Q10
• Omega-3 fatty acids
• Caloric restriction or intermittent fasting
• Cold exposure and saunas 
• Plant polyphenols (like those found in turmeric, berries, onions, herbs, green tea, and nuts)
• Resveratrol
• NAD+ boosters
• Resistance and aerobic exercise 

Key Takeaways

Biological age is becoming increasingly mainstream as a tool for assessing health and longevity. While there are many ways to measure biological age, DNA methylation and epigenetic age are at the forefront, as aging is known to increase the amount of methylated DNA. Although you’ll never be able to change the day you were born, altering aspects of your biological age is 100% within your control—and testing your biological age is the first place to start.

References:

Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361(9355):393-395. doi:10.1016/S0140-6736(03)12384-7

Fitzgerald KN, Hodges R, Hanes D, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021;13(7):9419-9432. doi:10.18632/aging.202913

Galkin F, Kochetov K, Mamoshina P, Zhavoronkov A. Adapting Blood DNA Methylation Aging Clocks for Use in Saliva Samples With Cell-type Deconvolution. Front Aging. 2021;2:697254. Published 2021 Jul 29. doi:10.3389/fragi.2021.697254

Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359-367. doi:10.1016/j.molcel.2012.10.016

Horvath S. DNA methylation age of human tissues and cell types [published correction appears in Genome Biol. 2015;16:96]. Genome Biol. 2013;14(10): R115. doi:10.1186/GB-2013-14-10-r115

Küchler EC, Tannure PN, Falagan-Lotsch P, Lopes TS, Granjeiro JM, Amorim LM. Buccal cells DNA extraction to obtain high quality human genomic DNA suitable for polymorphism genotyping by PCR-RFLP and Real-Time PCR. J Appl Oral Sci. 2012;20(4):467-471. doi:10.1590/s1678-77572012000400013

Moaddel R, Ubaida-Mohien C, Tanaka T, et al. Proteomics in aging research: A roadmap to clinical, translational research. Aging Cell. 2021;20(4):e13325. doi:10.1111/acel.13325

Panyard DJ, Yu B, Snyder MP. The metabolomics of human aging: Advances, challenges, and opportunities. Sci Adv. 2022;8(42):eadd6155. doi:10.1126/sciadv.add6155

Stoeger T, Grant RA, McQuattie-Pimentel AC, et al. Aging is associated with a systemic length-associated transcriptome imbalance. Nat Aging. 2022;2(12):1191-1206. doi:10.1038/s43587-022-00317-6