Circuits Around the Sun and Your Biological Age are Not the Same Thing: Here is Why This Matters
Measuring your biological age is more than just a vanity metric.
It solves a fundamental challenge of testing longevity drugs and healthy lifestyle interventions.
We simply live too long for clinical trials to conclusively say whether an intervention works. This is why we use proxies for age, including age-related disease onset, functional health measures and cellular / blood markers.
Tests of biological age are getting more accurate – and more accessible outside the lab.
The challenge is to prove that they are really measuring ageing, and not just biological changes which loosely correlate with our chronological age.
Comparing biological age measurements with population averages for chronological age is interesting. What biological age tests must do is predict outcomes, and to predict them to a level of accuracy that the effects of drug and lifestyle interventions can be measured accurately and cheaply.
As you’ll see below, this fascinating area of research is striving to answer several important questions.
Before I get to those, here is a quick overview of the original epigenetic biological age tests.
Steve Horvath and the Original Epigenetic Age Tests
Biological age tests have come a long way since the 2013, when Steve Horvath published details of his DNA methylation clock.
Our DNA has long strips of ‘CpG sites.’
Instead of complex sequences, these strips simply repeat C-G-C-G-C-G.
This makes it easy to spot errors, caused by methylation, which have not been repaired by our cells. What is more, the amount and types of errors at sites increases with age. Counting the CpG errors, then using a mathematical formula called a linear regression, is a predictor of chronological age.
With this information, it is possible to accurately predict 10 and 20-year mortality – at least for large samples of people. Your DNAm (DNA methylation) age will predict average onset of age-related diseases more accurately than your chronological age alone.
The Quest for More Accurate DNA Methylation Age Clocks
Biotech companies are working to fine tune biological ageing clocks.
Second generation clocks add many more methylation sites (up to 850,000 in some cases), alongside factors including histone status, RNA, glycans, data on chronological age and smoking / disease status (past and present).
With a giant dataset of tests, the algorithms are getting better too – with multiple services claiming theirs is the most accurate out there.
This means that results of blood, saliva, and urine tests of 2nd generation clocks match with ageing disease outcomes far better than the original Horvath clocks.
Some clocks including GrimAGE are only available to the scientific community. Others are developed for commercial use – with the market for self-administered tests growing significantly.
Alternatives to Methylation: New Approaches to Measuring Ageing
Adding measurements of other ageing markers.
Research continues, and biotech companies are fine tuning their models, and using different, blood protein levels, immune system markers and glycans to create even more accurate clocks. Add machine learning and more advanced algorithms, and the accuracy of clocks will only increase over time.
You’ll find more on the individual clocks and factors being measured further down this page. Before that, let’s cover the construct validity and replicability of results.
Measuring Biological Age: Construct Validity and Replicability
To be truly useful, biological age tests need to meet three criteria.
Firstly, measured biological age must be a better predictor of health outcomes (and functional abilities) than chronological age.
This is known as construct validity – the big question of whether lab-measured epigenetic age levels carry over into the real world. Results will only inform your chances of suffering from age-related conditions, based on the average onset of these conditions in the population as chronological age increases.
While finding out that you are biologically younger is welcome news, its predictive qualities work only at the population level – not for individuals.
Secondly, biological age tests then need to be replicable over time, and between samples taken at the same time and tested independently.
Thirdly, bio age tests need to show the effect of healthy ageing interventions. They must be accurate enough between samples to show how drug or lifestyle interventions affect ageing. For example, a test of mice before and after CR (calorie restriction) regimes need to show effects on their biological age markers.
Recent tests are accurate enough to cover the first two, and with accelerating accuracy, the third goal is within reach. Tests which measure the rate of ageing, rather than a snapshot, include DunedinPACE.
Commercial Bio Age Tests: What Kinds of Tests Can You Order?
Note: I’m not recommending individual tests or including any commercial links… This is my no-ads policy for the Age Well Times. Instead, you’ll find an overview of the types of test available to order, and how each one works.
The range of biological age tests available varies by country. I’ll list them (along with geographic coverage) at the end of this section.
Competition between commercial biological age test providers is heating up. Elysium, myDNAge, GylcanAGE and others charge between £200 ($250) and £400 ($500) for a single biological age test. You get discounts for multiple tests (for example second test a year later than the first).
Some require a simple saliva test, others a finger prick blood test – and still others require a blood sample via a healthcare provider. You’ll also need to add personal information, including age, sex, smoking status and disease status for the most accurate tests. Results can take weeks; the more accurate tests sample your DNA / blood markers multiple times and cross-reference the results.
Here is what will be tested, depending on which provider you use:
- DNA Methylation: Anything from 353 to 100,000 CpG sites are sampled, depending on the test.
- Histone Status: Proteins which wrap around your chromosomes, enabling expression of cell-specific parts of your DNA.
- Glycans: Proteins which are modified by sugar molecules by a process called glycation are measured from blood samples.
- RNA: Non-protein cellular messengers that correlate well with age-related diseases.
- Telomere Length: The endcaps of your chromosomes shorten over time, affecting cell replication and senescence.
- Blood Markers: Commonly used blood markers include creatine, c-reactive protein, albumin, and alkaline phosphatase.
- Personal Information: Your own history, disease status, smoking (past or current) and sex.
Commercial Biological Age Tests (and where they ship to)
MyDNAge: This is a Horvath clock test. It uses 2,000 CpG sites, using a proprietary ‘SWARM’ (Simplified Whole Panel Amplification Reaction Method) system from either blood or urine using a home test kit. Available in the USA, Canada, Europe (inc. UK), and Australia.
GlycanAge: A home finger-prick blood test kit. 27 Glycans are measured, showing the damage from sugars on proteins that accumulate with age. You get a follow up consultation when the results arrive (3-5 weeks). Claims to be the most accurate commercially available biological age test. Ship to UK, USA, and Canada – plus worldwide with a postage surcharge.
Index from Elysium Health: This saliva sample test is a second-generation Horvath clock. It samples 100,000 CpG sites, using a custom chip and algorithm. Dr Morgan Levine spearheaded its development. This test only ships to the USA and Canada at the time of writing.
Do Not Age Biological Age Test Kit: Another saliva test, which combines a DNA methylation clock with 100 DNA reports covering diet, immunity, stress, and others. Claims memory, hearing and eye age tests are included (though does not explain more).
Novos Age: USA only for this three-factor test. It includes not only a snapshot epigenetic clock test, but a rate of ageing measure DunedinPACE). In addition, you get a telomere length test. It is a shame that this one is not available in the UK, as the three-in-one test is at around the same price as single tests from other providers.
TruAge: Two different tests are available from TruAge. The comprehensive TruDiagnostic is an epigenetic test covering 850,000 sites. This also measures telomere length and provides immune system counts. TruAge Pace uses the DunedinPACE rate of ageing test). Ships worldwide.
This is a dynamic commercial marketplace. I will cover other commercial providers as the market develops.
Biological Age Tests: Full List of Factors
Below is a list of factors which can be measured as markers of biological age.
They range from prognostic tests (used to predict response to treatments), physical tests and those that are specific to the function of an organ. Some are used in the lab, others in medical practice.
I look forward to updating this list (and fleshing out individual factors) as the field of biological age measurement moves forward.
- Hand Grip Strength
- Walking Speed
- Timed Up and Go
- Standing Balance
- BMI / Muscle Ratio
- Bone Mass
- Blood Pressure
Organ Health Surrogates:
- Creatine (Kidney Function)
- Liver / Bile Metabolism
- Troponin (Structural, Heart)
- Transaminase (Liver Function)
- NT-PRO BNP (Heart)
- Blood Count
- Inflammation Markers
- Skin Biome Markers
- Gut Biome Markers
Cellular Senescence Markers
- SASP (Senescence associated secretory phenotype)
- SAFI (Senescence associated histone foci)
DNA Methylation Measurements
- Horvath Clock
- Weidner Clock
- Hannum Clock
Epigenic Clock Measurements (2nd Generation)
- DNAm PhenoAge
- DNAm GrimAge
Novel Markers / Current Research
- Cystokine / Histone Modifications
- Chromatin Remodelling
- Extracellular RNA
- Micro RNA
- GDF-15 (Proxy for mitochondrial disfunction)
- High Throughput Analysis
Wrapping Up: Should You Get Your Biological Age Measured?
I’m going for it.
By the time you read this my first test will be on its way. This triggered some personal worries. These are noted in a separate post over on my blog.
There is a giant caveat with bio age testing.
They are not predictive of your individual health outcomes – only your chances of age-related illness vs the population.
If you accept that, then setting a benchmark will give you a goal to work towards.
Whether I’m older or younger than my chronological age will be great to know. Having a goal to be younger (biologically) in one- or two-year’s time – that will be worth the price of testing many times over.
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