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Biological “clocks” based on epigenetic age have been around for just over a decade. Steve Horvath, a PhD scientist at UCLA launched the field with his original 2013 pan-tissue clock that predicted chronological age with head-turning accuracy. Other researchers subsequently crunched their own epigenetic (DNA methylation) data and applied advanced mathematical models to similarly predict age with their own “clocks”, resulting in a suite of available epigenetic age assessments – each with similarities but also notable differences. Some of these are more widely available for non-researchers to use than others.
In this article, I want to introduce you (or reintroduce you, if you’ve come across it before) to one such assessment – the DNAm PhenoAge clock, and more specifically its sister-tool, the PhenoAge Calculator. The PhenoAge Calculator is widely available to everyone, is free to use, and requires only input from a handful of easily-accessible and inexpensive lab tests to get the data you need to input into the calculator..
The PhenoAge Calculator is Based on the Original DNAm PhenoAge Clock Analysis
Firstly, let’s understand where the PhenoAge Calculator comes from.
Dr. Morgan Levine, a scientist with past positions at UCLA and Yale, now incidentally a principal investigator at the Jeff Bezos-funded Altos Labs, developed the DNAm PhenoAge Clock with Horvath while working under his mentorship at UCLA. They published it in 2018. The intention was to improve on his 2013 pan-tissue clock by incorporating biologically-relevant phenotypic biomarkers into the mix, in addition to chronological age. These biomarkers could be influenced by diet and lifestyle and therefore potentially affect the aging journey. These markers are ones that you are probably familiar with – at least some of them – even if you’re not a clinician.
Levine first pulled together a simple set of 9 standard blood biomarkers, that when crunched in an algorithm she developed, predicted age AND morbidity and mortality with stunning accuracy.
In fact, what’s interesting to me is that these biomarkers are incredibly common in clinical practice, we glance at them daily and most are not given much weight, frankly, in clinical decision making (RDW, anyone?) and here they are in a shiny new light, proving themselves essential in the longevity conversation. And not just in the PhenoAge, but clocks like TruDiagnostic’s OMICmAge have also identified RDW as a standout predictor.
But Levine’s PhenoAge clock didn’t just incorporate the additional phenotypic biomarkers – 9 of them to be precise: albumin, creatinine, glucose, CRP, lymphocytes, mean cell volume, red cell distribution width, alkaline phosphatase, and white blood cell count – it actually started off with them as the first step in developing an age prediction. Even before DNA methylation entered the picture. After filtering through many, many possible biomarkers from the massive NHANES dataset, these 9 biomarkers formed the tightest, validated age prediction.
It was only after this stage was complete that the “phenotypic age” from the step above was mapped onto DNA methylation data to identify which DNA methylation sites could then be used to predict this same phenotypic age. This DNA methylation-based predictor was then named DNAm PhenoAge.
Hopefully we’re all still with me? It’s a little in the weeds, but walking through this process helps explain why the PhenoAge Calculator is useful – it is based on the original pattern of phenotypic biomarkers that Levine and her colleagues created before they mapped it to DNA methylation. This means that we’re not really losing any of the predictive power of the PhenoAge algorithm by simply using these original clinical phenotypic biomarkers.
PhenoAge is unique in this regard – none of the other epigenetic age clocks make it possible for us to use their model in a “DIY” fashion like this.
How Can We Use the 9 Phenotypic Biomarkers in the PhenoAge Calculator?
In order to DIY the PhenoAge algorithm using the above phenotypic biomarkers, we need to first measure an individual’s phenotypic biomarkers and then enter them, along with their chronological age, into the PhenoAge Calculator (an Excel spreadsheet). Let’s break down these two steps:
1. Measure phenotypic biomarkers
You can measure the 9 needed biomarkers using three standard laboratory tests:
- Comprehensive Metabolic Panel (CMP)
- Complete Blood Count (CBC)
- CRP (or hsCRP)
As I said, these are standard labs that physicians are looking at every single day. If you’re not able to order labs directly, you can have your patient/client ask their primary care physician for these tests, or they can also source them from a direct-to-consumer lab testing company. Here is one such direct-to-consumer lab testing company I recommend, and who have kindly created the lab test bundle needed for the PhenoAge:
Younger You PhenoAge Labs Only Bundle
Bundle includes standard biochemistry labs, the results of which can be plugged into the PhenoAge calculator above.
2. Identify and enter biomarker values into the calculator
When you receive the blood test results, identify the values for albumin, creatinine, glucose, C-reactive protein (CRP), lymphocytes, mean cell volume (MCV), red cell distribution width (RDW), alkaline phosphatase (ALP), and white blood cell count.
You will need to check the units used for each of these values and make sure they are what is required in the calculator. If they are in different units, they can be converted using online conversion tools.
Enter the values for those biomarkers, along with the chronological age, into the blue bolded “Input” line of the spreadsheet (see below). Once all the input fields are populated, a biological age is reported in the bottom right hand corner. That’s it!
Access the PhenoAge Calculator HERE.
A Tip for International Readers Using SI units
It’s actually possible for anyone using international labs that are measured in SI/metric units to input those directly into the calculator on the horizontal line titled cInput. This bypasses the step of having to convert to US customary units first.
A Recap – How Does DNA Methylation Relate to Aging?
The process of aging appears in many forms in the body. While we only have the dubious luxury of using what the mirror, or perhaps our joints, tell us as a way to catalog our aging journey, scientist have been investigating the biochemical impacts (signatures, or “hallmarks”) of aging to try to better understand its process and effects.
One of the types of biochemical alterations in aging is found in our epigenetics – the layer of biochemistry that sits on top of our genes and directs how genes are “read.” It’s the biochemical software, to our DNA hardware, if you will. The most well-studied of these epigenetic biochemical phenomena is called DNA methylation, and is what has been used to develop epigenetic age clocks since it turns out that there are some very predictable changes in DNA methylation that occur with age.
How Does the PhenoAge Calculator Compare to Other Measures of Epigenetic Age?
If you would like to read an overview of the epigenetic age clocks and the most recent research data published on them, I recommend this blog published November 2023: New and Notable Studies Using Epigenetic Biological Age Clocks.
In addition, while I do use the PhenoAge calculator with my patients as an additional data point in their comprehensive evaluation, I also often lean on the 3rd generation epigenetic clock – the Pace of Aging clock – along with the Biological Age Quiz, which provides additional dietary and lifestyle information to improve epigenetic age (and which we have preliminary data correlates well with the Pace of Aging results).
Important to note that, as with any of the biological age “clocks,” we have to approach them rationally. Hitching our wagon to, say, these nine biomarkers, and thinking that we could reach 120 years old (or escape velocity to immortality!) if we do everything we can to optimize them isn’t the way to go. And I do see this thinking in certain corners of the longevity conversation – there’s a lot of emotion around age, after all. While it can be motivating in a good way, optimizing healthspan extends well beyond this rather myopic conversation. I do think they are relevant and important in the overall goal of improving healthspan and lifespan, along with many other factors, as we try to bring out in our other Younger You content.
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