The most precise measure of biological age: The science behind Index


Elysium’s biological age clock, Index, is the most precise measure of epigenetic age available and a more accurate predictor of overall health than a previous leading measure, DNAmPhenoAge. Why is a measure of biological age—and the accuracy of such a measure—important? 

In order to develop interventions that support long-term health and wellness, we need reliable measures to track the effect of interventions. While chronological age has typically been relied upon in the past as correlative with health and wellness, it’s become apparent that not everyone ages at the same rate. An accurate measure of the biological and physiological hallmarks of aging can offer enormous potential for personalized health protocols.

Improving on prior biological age tests:

Along with Morgan Levine, Ph.D., Elysium’s bioinformatics advisor and a professor of pathology at Yale, the Elysium team conducted an experiment using available technology to test the reliability of existing epigenetic clocks. The ensuing discovery was startling—a single sample processed repeatedly resulted in epigenetic age estimates that varied dramatically, up to 25 years apart. Our team set out to develop an improved measure that would minimize this variation and deliver greater precision and accuracy.

Location Yale University
Protocol Examines global methylation patterns across more than 100,000 sites for superior precision and accuracy
Results Index is a better predictor of epigenetic age than earlier measures

Result: APEX

Published biological age clocks such as DNAm PhenoAge typically look at hundreds of sites on the genome. Elysium’s algorithmic platform for epigenetic examination (APEX) improves upon these clocks by examining global methylation patterns across more than 100,000 sites for a truly robust DNA methylation-based measurement. APEX has been shown to output results that dramatically increase precision and accuracy relative to other published DNA methylation measurements.

Testing Index for Repeatability

In order to improve Index’s repeatability, we updated the academic model of biological clocks, which are built to detect signals at the population level rather than the individual level. These clocks measure methylation at hundreds of sites, and we determined that this small subset of sites is too sensitive to experimental variation at an individual level. Instead, Index utilizes methylation at over 100,000 sites and this much larger subset provides a stronger signal and improved repeatability. We then conducted our own internal validation, which entailed putting Index through a battery of tests to account for circumstances that arise when data is based on saliva samples—we subjected the samples to many of the variables that can happen when people are living their lives—forgetting the saliva sample on your desk for a week, temperature changes that occur during shipping, drinking coffee before taking a sample.

What’s Next for Index: New Measures

We’re at work on an updated version of Index that includes more than 5 subsystems—amongst them the heart, brain, kidneys, and liver. This new version of the test will be able to indicate the degree to which each of these parts of your body is contributing to your overall biological age, allowing you to target your health and wellness efforts towards particular aspects of your life that affect these systems.