Researchers can accurately determine how old a person is based on the calibration of the DNA. To do this, they use a so-called epigenetic clock. Master’s student Thomas Jonkman has now, nine years after the discovery, unravelled how this clock exactly works: it turns out to keep track of the ageing of our immune system. With this knowledge, the clock can be applied in a much more useful way, for example to detect people with a vulnerable immune system.

The epigenetic tuning of our DNA, which genes are ‘on’ or ‘off’, is determined by molecular dimmers attached to the DNA. This DNA tuning changes throughout life. Using machine learning, researchers have developed a so-called epigenetic clock based on such changes. With this, a person’s age can be determined very accurately on the basis of a DNA sample. This is useful for forensic research, but biomedical applications lagged behind because the mechanism of the clock was not yet understood.

Old and young immune cells

Leiden master’s student in Biomedical Sciences Thomas Jonkman has now discovered how the clock works: it shows you how old your immune system is. “Using blood samples from over 3,000 people, we investigated exactly which biological processes change when this clock ticks. These turned out to be processes specific to young, fresh immune cells or old, exhausted immune cells,” says Jonkman. In other words, the clock determines a person’s age on the basis of the ratio of old to young immune cells in the blood.

Biological age

This research is an important step in the application of the clock, says Professor of Population Epigenetics Bas Heijmans. “We know that in some people, the age estimated by the clock is older than the actual age, and vice versa. Are these people therefore biologically younger or older?” To find out whether this difference is a measure of health, as a next step the researchers want to focus on whether they can use the clock to detect people with vulnerable immune systems. ” We learned from the corona pandemic how important that is,” says Heijmans. Researchers like Jonkman, who can cleverly combine and analyse big data, are crucial to such research. He will therefore continue the research as a PhD student in Heijmans’ group.

The research was published in the prominent scientific journal¬†Genome Biology¬†and was made possible by the American National Institutes of Health and BBMRI-NL, a NWO-funded collaboration between Dutch research institutes to make research material and data from population studies available for health research. The data analyses were done at SurfSara’s high-performance computing facilities.