Biological Age Tests: DNA Methylation? vs Mogan Levine’s “Phenotypic Age”

As we start inquiring about biological age tests, we often hear about “DNA methylation” and Morgan Levine’s “phenotypic age (or biological age)” calculator.  Those two phrases are associated with the two primary methods used today to calculate the “biological age”: based on DNA methylation and or blood lab test results.     

DNA methylation is simply a way our body tags our DNA in order to organize our genetic code, just as we tag our textbooks with Post-Its to organize learning material.  Steve Horvath, a professor at UCLA, discovered that the pattern of DNA methylation changes as we age, and we can observe those patterns to calculate our biological age. 

Morgan Levine, a professor at Yale, looked into how more “understandable” blood test results can be used to calculate biological age (or a.k.a., “phenotypic age”).  

       

What is DNA Methylation?

Figure 1: DNA methylation is a way for our body to express or silence our gene expression.

Our DNA is stored in a compact form called a chromosome.  In order for a specific genetic code to be accessed and used, the corresponding part of the DNA needs to be unwound as shown in Figure 1.  When a part of the DNA is methylated, that part of the DNA cannot be accessed or used.  DNA methylation is similar to tagging our textbooks with Post-Its, as shown in Figure 2.  By tagging with Post-Its, we are communicating with ourselves whether to review or not review specific parts of the book.      

Figure 2: “DNA methylation” is similar to “tagging” our textbooks with Post-Its. 

What is a DNA Methylation-based Biological Age Test?

Methylation-based Biological Age Test calculates your biological age by examining your DNA-methylation patterns observed in your blood or urine samples. In general, the higher the DNA methylation, the higher your biological age.

Why is a DNA Methylation-based Biological Age Test reliable?

Professor Steve Horvath at UCLA published his findings in 2013, showing that the extent of DNA methylation in our tissues correlates with our chronological age with an unprecedented correlation of 0.96 (See Figure 3); his work was discussed in the prestigious journal Nature.  A correlation of 1.0 means a perfect correlation between two factors, and 0 means no correlation at all.  Other strong biomarkers in the past, such as the length of telomeres, had a correlation of at most 0.5 to 0.6. 

Figure 3: This figure was borrowed from Steve, Horvath, “DNA methylation age of human tissues and cell types,” Genome Biology, 14:R115 pg.4.  “M.age” stands for age prediction based on DNA methylation. 

Where can I access DNA methylation-based Biological Age Tests?

Here are some of the commercially available DNA methylation-based biological age tests today:

Elysium Biological Age Test

The Epimortphy MyDNAge

What are blood work-based Biological Age Tests?

There are other blood biomarker-based clocks including Morgan Levine’s biological age based on 9 biomarkers.  Levine’s biomarkers are tabulated below in Table 1:  

Table 1: Biomarkers for Levine’s phenotypic age calculator.  This table was borrowed from Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA, Wilson JG, Reiner AP, Aviv A, Lohman K, Liu Y, Ferrucci L, Horvath S. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018 Apr 18;10(4):573-591. doi: 10.18632/aging.101414. PMID: 29676998; PMCID: PMC5940111.

You need to plug in those 9 biomarker values from your blood test, and calculate Levine’s biological age, or “phenotypic age” as Levine calls it. 

Why is a blood lab test based-Biological test useful?

The biological age calculated by blood test results is particularly useful because we have targets that are easily understandable.  For example, if your inflammation biomarkers like C-reactive protein are elevated, you can change your diet or apply sunscreen to reduce inflammation. 

Where can I access blood lab test-based-Biological Age Tests?

Here is the link to a Levine’s biological age calculator that I have created following her paper.

Additionally, there are more nuanced, proprietary biological age calculators such as the one offered by InsideTracker.  Here are lists of biomarkers InsideTracker uses to calculate its clients’ biological age:

Figure 4: Biomarkers used by InsideTracker to calculate the “biological age”

How biological Age Test results can be used as a metric to improve our biological age:

Professor Horvath published a paper in 2016 showing that behavioral and lifestyle changes, including consuming healthy diets and exercising, can slow down the progression of the “biological age” determined by DNA methylation.  

For blood work lab test-based biological age test results, we have more “tangible” lifestyle changes we can make to improve our biological age.  For example, If your LDL level is contributing to a high “biological age,” you can focus on changing diets with low LDL cholesterol levels.

Could NAD+ supplementation improve our biological age?

NAD+ deficiency, as discussed in Nature, can abnormally alter DNA methylation patterns, accelerating the biological aging process.  As I explain in later articles, many of those blood lab test results can be improved by addressing NAD+ deficiency.        

It would be worthwhile to take a look at what NAD+ is in the next article.

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