How Is Biological Age Measured and Estimated?

1. There is no single established measure of biological age. Biological age is estimated from biological characteristics associated with aging rather than measured directly. No single biomarker, combination of biomarkers or estimation method has been validated as the best measure of an individual’s biological aging status.

2. The choice of biomarkers matters. Biological-age models can use clinical, physiological, cellular and molecular measurements. Ideally, biomarkers should provide information beyond chronological age alone, relate to underlying aging processes rather than simply reflect disease, and be suitable for reliable and repeated measurement.

3. Molecular and genetic markers provide additional ways to assess aging. The review examines genomic, epigenetic and transcriptional biomarkers, together with the potential contribution of genetic variation and polygenic risk scores. DNA methylation is used to construct epigenetic aging clocks developed for different purposes.

4. How biomarkers are combined can change the result. Mathematical approaches range from traditional statistical models to the Klemera–Doubal method and newer machine-learning approaches. Their performance varies between studies and health outcomes, and no single approach has consistently performed best.

5. Machine learning expands the possibilities for biological-age estimation. It can analyze large and complex datasets, including conventional biomarkers and medical imaging, but complex models can be difficult to interpret and may overfit the data used to develop them.

6. Biological aging may not follow a simple linear pattern. Aging patterns may differ between individuals and parts of the body, and some biomarkers may change nonlinearly with age. Models that include only measurements with a simple linear relationship to chronological age may miss useful information.

7. How biomarkers are measured also matters. Differences in laboratory and measurement methods can affect biological-age estimates and make studies difficult to compare. Telomere length is one example where measurement technique and error can affect reliability and interpretation.

8. Biological-age estimates can provide information about health outcomes. Measures reviewed were associated with morbidity, mortality and functional decline, and some provided information beyond chronological age alone, but findings were not consistent across every method, population or outcome.

9. There is still no universally accepted standard. Accuracy and usefulness depend strongly on the selected biomarkers and the method used to combine them. Greater standardization and further research are needed.

Biological age is increasingly used to describe differences in how people age. But a biological-age number is an estimate calculated from selected biological information, and different methods may measure different aspects of aging.

This is particularly relevant as biological-age tests and online calculators become more widely available. One test may use clinical biomarkers, another DNA methylation, and another a more complex computational model. Their results should not automatically be considered equivalent.

When interpreting a biological-age result, three questions are particularly useful: What was measured? How was the result calculated? What has that method been shown to predict?

For longevity medicine, the value of biological-age assessment will depend on whether these measurements can reliably reflect meaningful aging-related changes, health risks and changes over time.

Current biological-age methods provide potentially useful information about aging, but they are not interchangeable.

The interpretation of a result depends on the biomarkers measured, the method used to calculate the estimate and the outcomes against which the method has been evaluated.

At present, there is no single accepted test or model that definitively measures an individual’s overall biological age.