I am sure that we have all encountered individuals who look younger than their actual age. Perhaps you may even be lucky and appear younger than your chronological age yourself! Or someone in your family might be. But why is that?
Chronological vs Biological Age
To understand ‘age’ better, it helps to define what we mean when we discuss about the different types of age.
Chronological age refers to the years a person has been alive for. The latter, the biological age looks at a number of pre-defined biomarkers to estimate someone’s age at a cellular level.
There is currently no pre-defined criterion for establishing someone’s biological age. There are different frameworks as we will see later in the article, but nothing is standardized yet. This is of course due to the relative novely of anti ageing medicine.
Biological Age Testing
First Generation Tests: Horvath Clock Test (2013)
The first ever test which is now called the first generation test, was the Horvath clock test. This was introduced in 2013 as a biological age predictor. It measures 353 DNA methylation markers that strongly correlate with how old a person is in years.
While this marked a significant advance—demonstrating that DNA methylation sites could reliably predict age—these early tests were less adept at revealing an individual’s health risks or predicting age-related illnesses. In other words, it can be useful to put a metric on the biological age, or how many ‘birthdays’ someone experienced at a cellular level, but is not useful in providing a clinical benefit. It also does not account much for lifestyle and health variables that might accelerate or decelerate ageing.
Second Generation Tests: PhenoAge (2018)
The limitation of the Horvath clock test led to further research and eventual development of better biological age predictors. One such example is the PhenoAge, developed by Levine et al in 2018. This test provides a more nuanced view of health status and risk.
These tests typically incorporate broader biomarker sets and clinical indicators (e.g., inflammatory markers, metabolic measures, and blood-based parameters) in addition to DNA methylation.
By doing so, they shift the focus from simply matching numerical age to assessing susceptibility to morbidity and mortality. The biological age estimates are refined by integrating health-related data, thereby offering us, clinicians and researchers deeper insights into an individual’s risk of chronic disease and overall physiological resilience.
|
Test Name |
Purpose |
Biomarkers Included |
|---|---|---|
|
PhenoAge (Levine et al., 2018) |
Estimate biological age with emphasis on morbidity and mortality prediction |
Clinical blood biomarkers used to derive the DNA methylation model: • Albumin • Creatinine • Glucose • C-reactive protein (CRP) • Lymphocyte percentage • Mean cell volume (MCV) • Red cell distribution width (RDW) • Alkaline phosphatase (ALP) • White blood cell count (WBC) |
Third Generation Tests: DunedinPACE (2022)
The DunedinPACE test is the latest biological age biomarker test and the one you may have heard about the most in the press. This is the test used by Bryan Johnson in his claim that his rate of ageing is now .64 compared to 1 or even a faster than one of ageing in some people. As you may have noticed, instead of providing a biological age, this test gives out your rate of ageing instead.
A rate of ageing such as this becomes most useful when measuring the impact of specific interventions.
For instance, if someone implements a dietary change or adopts a new exercise regime, or better sleep patterns a third-generation test can help. It can help more sensitively track the resulting slowdown in their biological ageing processes. If someone implements the opposite changes, a test such as this could measure the new acceleration in their own ageing.
This makes third-generation clocks potentially more powerful for guiding personalised anti-ageing interventions such as the ones we are striving to offer at our clinic. Regularly taking the DuendinPACE test could assess if the thought to be healthy changes you’ve just made have actually had any impact at your cellular level or not. It can highlight real-time fluctuations and trends in ageing rather than delivering a static estimate.
|
Test Name |
Purpose |
Biomarkers Included |
|---|---|---|
|
DunedinPACE (Belsky et al., 2022) |
Measure the rate of biological ageing over time |
DNA methylation-based algorithm: • 19 CpG sites predictive of pace of ageing • Functional measures are also used in validation but not directly inputted into the test: VO₂ max, Grip strength and FEV1 volume (lung function) |
Summary of biological age tests
|
Generation |
Example Test(s) |
Purpose |
Biomarkers Used |
Key Strengths |
Limitations |
|---|---|---|---|---|---|
|
First Generation |
Horvath Clock (2013) Hannum Clock |
Estimate biological age to match chronological age |
DNA methylation at predefined CpG sites |
High correlation with chronological age Groundbreaking at time of release in 2013 as this was the first of its kind |
Limited prediction of health outcomes Fun to find out, but not much use in a clinical context |
|
Second Generation |
PhenoAge (Levine et al., 2018) GrimAge |
Predict morbidity and mortality risk |
DNA methylation + clinical blood markers (e.g. CRP, glucose, creatinine, albumin) |
Better health and disease prediction Incorporates functional health data |
Provides a static biological age More data needed for accurate use |
|
Third Generation |
DunedinPACE (Belsky et al., 2022) EpiAgePublic (Cheishvili et al., 2025) |
Measure the rate of ageing over time |
DNA methylation + functional biomarkers (e.g. VO2 max, FEV1, grip strength) |
Tracks speed of ageing Sensitive to lifestyle or therapeutic interventions |
More complex and can be more expensive to perform. Standardisation and validation are still developing |
Conclusion
In conclusion, understanding and trying to improve your biological age can get interesting. Now that we know how to better measure it, as opposed to just relying on chronological age, we can explore and target possible interventions for personalised preventative healthcare and longevity medicine.
