Epigenetic clocks are becoming a real breakthrough in health and longevity.
They are currently the best tools we have to assess our biological age. In other words, how old we really are.
They have considerable advantages over classic ways to “assess your global health,” such as doing a blood test.
What are epigenetic clock tests?
Did you know you have two ages? Your chronological age and your biological age.
Your chronological age is based on your birth date. Chronologically, you might have been alive for 50 years. But, if you’ve been eating a lot of bad foods, do not exercise enough and you smoke, you may be the biological equivalent of a 62 year old, for example.
Epigenetic clocks are intended to determine your biological age. And this is important: your biological age is strongly correlated to your risk of dying (mortality risk) and your risk of getting aging-related diseases.
Epigenetic clocks versus classic screening
Determining your biological age is very interesting, because in general, doctors don’t have good tools to assess your global mortality and disease risk.
They have to rely on somewhat blunt tools, like measuring your weight, blood pressure, waist circumference, or by taking an MRI (which, for example, detects tumors when they are already too big) or by doing a blood test.
Blood tests are often done as medical health checkups, but unfortunately they’re not very refined tools to assess your health and mortality risk. For example, they look at cholesterol, inflammation (e.g., CRP), or kidney biomarkers, but many people with “normal cholesterol” levels, normal CRP levels, or normal kidney function still can be (very) unhealthy.
Blood tests can nonetheless be useful, but mainly to detect severe abnormalities. In that sense, a lot has to go wrong before your liver enzymes are increased, or CRP or kidney metabolite levels are too high (we explain more about blood testing here).
Epigenetic clocks could provide a much better overall picture of your health. They can provide an in-depth, global assessment of your mortality and disease risk.
How do epigenetic tests work?
Epigenetic clocks look at the methylation patterns on our DNA.
Methylation of the DNA is part of what we call the “epigenome.” The epigenome determines which genes are switched on or off.
One way to switch off genes is by adding small atom groups to the DNA (we call these small atom groups or molecules, methylgroups).
When a specific part of the DNA is “covered” with methyl groups, this part of the DNA becomes silent: the DNA, encoding for a protein, cannot be translated into protein.
Putting methyl groups on DNA is one way the epigenome regulates gene expression. This gene expression (and silencing) is very important.
All our cells have the same DNA but a liver cell is a liver cell because only liver cell genes are switched on (and not the heart genes, stomach cell genes, neuronal genes, and so on). A neuron is a neuron because the liver, heart and kidney genes are switched off by the epigenome.
NOVOS has the best epigenetic aging test that science offers in NOVOS Age. It has 3 tests in 1:1
- Rate of aging via the DunedinPACE epigenetic clock, developed by Columbia University and Duke University scientists. This is the primary emphasis of NOVOS Age
- Biological age according to an epigenetic clock collaborated on by Harvard scientists
- Telomere length, which protects your DNA and shortens with age
Epigenetic dysregulation and aging
However, the older we get, the more these methylation patterns get disturbed. This contributes to aging.
For example, housekeeping and repair genes that should be switched on are switched off, while cancer and inflammation-promoting genes are switched on.
The methylation patterns also change, not only because of aging, but because of many other factors.
If you smoke, some genes will be methylated more, and others less.
If you drink a lot, specific genes involved in alcohol detoxification will be epigenetically switched on.
If you have a lot of stress, stress-related genes will be demethylated so they can become more active.
The epigenome thus provides a sort of global blueprint about our general health and how old our body really is.
Epigenetic clocks look at hundreds of different spots in the DNA and see if there is a methyl group or not (more specifically, they look at whether a specific base pair, namely a cytosine, is methylated or not).
Mathematical or AI algorithms then correlate those methylation patterns with mortality and health.
Various epigenetic clocks already exist, such as the ones developed by Dr. Steve Horvath and his team, like the PhenoAge (R), GrimAge clock (R), and DNAmAge clock (R), while there are also many other clocks, like the Hannum clock (R).
Various companies are developing their own versions of clocks. But it’s important that these novel clocks are validated in scientific studies, preferably studies carried out by other scientists than the ones who developed the clock.
For example, NOVOS Age uses one of the most studied epigenetic clocks, with more than 45 scientific studies conducted at 30 independent research labs across the world. The clock, DunedinPACE, has the best objective measures of all biological age clocks available, which you can learn more about here.
NOVOS Age vs. Other Biological Age Clocks
|Attribute||NOVOS Age Clock||Saliva-based Clock by Celebrity Scientist's New Startup||Other tests|
|Tissue Collection||Blood from a small poke of a finger, a method that is more accurate than via saliva||Saliva from a cheek swab, a method that is generally not very accurate||Blood collection methods that are invasive and far more uncomfortable that via small pokes of fingers|
|Sample Size||Samples from more than 20,000 humans||Samples from more than 8,000 humans||Samples typically from fewer than 2,500 humans|
|DNA Methylation Technology||Built using the modern MethylationEPIC array that measures 850,000 DNA sites and tests your sample on that same technology||Built using the modern MethylationEPIC array that measures 850,000 DNA sites but does not test your sample on that same technology||Built using older arrays that only capture 27,000-450,000 DNA sites|
|Chronological Age Range||8-102 years||18-100 years||Less expansive age range often lacking individuals 90+ years of age|
|Diversity||Significant diversity across ethnicity, race, and sex, all supported by many peer reviewed publications||Diversity across ethnicity, race, and sex, but without support of peer reviewed publications||Insufficient representation across ethnicity, race, and sex and without support of peer reviewed publications|
|Test Reliability||Optimized to be reliable across repeat measurements, with published and peer reviewed best-in-class ICC values (accuracy) >.96 for all three algorithms||Claims of being optimized to be reliable across repeat measurements without disclosing ICC values||Exhibit high test-retest error rates|
|Model Type||3rd generation (latest) clock, the only one trained on longitudinal analysis (people across their lifetimes), the best way to track biological age as shown in publications and tested via peer review||Self-claimed "novel" method-based model that lacks publications, peer review, and head-to-head comparisons against other clocks||1st generation (oldest) model trained to simply estimate chronological age instead of biological aging|
|Outputs and Analysis||Three: 1) 3rd generation Pace of Aging via DunedinPACE, 2) Biological Age, and 3) Telomere Length||One: A less accurate output of biological age||A single, less accurate output of biological age|
|Creators of Clock||A top team of Duke University and Columbia University scientists with peer reviewed publications||A start up company without publication of the algorithms, thus lacking scientific scrutiny|
|Number of Studies||45+ published studies by 30+ longevity scientists' labs across the world||Zero published studies|
|Immune Cell Controls||Published and Patented Advanced 12-cell immune deconvolution methods (cell changes won't impact accuracy, which is common in saliva and makes blood samples better)||No controls||No controls|
|Studies that prove accuracy in different ethnic groups||Algorithms validated in the Family and Community Health Study of African American Families study, MESA (Multi-ethnic Study of Atherosclerosis), Cebu Longitudinal Health and Nutrition Survey (CLHNS Phillipines), Northern Finland Birth Cohort 1966 Study, Health and Retirement Study, the Normative Aging Study, the Framington Heart cohort, TILDA (the Irish Longitudinal Study of Aging), and many more.||No studies||No studies|
|Studies that show relatonship to outcomes||Algorithms have been validated in the Health and Retirement Study, the Normative Aging Study, the Framington Heart cohort and more.||No studies||No studies|
|Studies that show change with validated anti-aging interventions||The only algorithm proven to respond in a significant way to validated anti-aging interventions such as caloric restriction (Published in Nature)||No studies||No studies|
|Include Clinical Covariates||21 clinical covariates and telomere length||No clinical covariates||No clinical covariates|
|Comparisons to other algorithms||Comparisons in the FHS study and in the Health and Retirement Study show superior results||No published comparisons||No published comparisons|
|Shares actual data on precision (ICC values)||See ICC values with comparisons in the FHS study.||No data||No data|
Can I reverse my epigenetic age?
Recent studies have shown that you can epigenetically become younger by adhering to a healthy lifestyle, and even with certain supplements and drugs (R,R,R). (You can learn more about the epigenome and aging here).
For example, microdosed lithium, alpha-ketoglutarate, NMN, and glycine can all improve the epigenome.
We talk more about epigenetically reversing aging here.