DNA methylation

DNA methylation is a chemical tag attached to DNA that helps decide whether a gene is switched on, and whose pattern shifts in predictable ways with age. The sequence of the DNA itself does not change; what changes is which parts of it are marked.

Because the marks respond to circumstances as well as to time, they were an obvious candidate for a measure of how a body is faring rather than how many birthdays it has had. Hundreds of thousands of sites can be read at once from a blood or saliva sample, and statistical models trained on those readings became the epigenetic clocks now sold as biological age tests.

Two properties make the measurement harder than it appears. Methylation differs between tissues, so a reading from blood describes blood, not the body as a whole. And it moves on short timescales in response to ordinary events, which is a virtue if the goal is to detect change and a problem if the goal is a stable number.

The measurement is also sensitive to how the sample was handled. A 2022 paper in Nature Aging reported that technical noise alone produced differences of up to nine years between repeat measurements of the same sample for six prominent clocks.