The Zhang Clock Portends Near-Perfect Age Prediction

Researchers investigated whether a perfect DNA methylation-based measure of biological age is theoretically available. And they reported the results of their study in a 2019 paper published in Genome Medicine.

Biological age is not always the same as chronological age. In fact, persons with the same chronological age can vary in health, especially in later life.

“DNA methylation changes with age,” reads the abstract of the paper. “Chronological age predictors built from DNA methylation are termed ‘epigenetic clocks.’” The lead author of the paper is Qian Zhang, now at Wellcome Sanger Institute.

DNA methylation is a biological process by which chemical tags are added to the DNA molecule. It can change the activity of a DNA segment without changing the sequence. The methylation marks fundamentally change the way individual cells use the genome.

Epigenetics is the study of chemical and structural modifications made to the genome. The changes do not alter the DNA sequence. But they are still passed along as cells divide. And they can influence how genes are expressed.

Epigenetic clocks include the Horvath, Hannum, and Levine aging clocks, described in previous posts. They measure aging processes at the molecular level.

The first epigenetic clocks were developed 10 years ago. A recent review article was published by the Simons Foundation. It explains, “scientists have developed dozens of new versions, constructed from different methylation sites and fine-tuned to different purposes.”

For this Genome Medicine study, the researchers used thousands of blood samples and hundreds of saliva samples from test subjects of all ages (ranging from 2 to 104). Then the researchers built different age predictors based on DNA methylation analysis. And they trained the predictors with the sample data, using sophisticated statistical techniques. Finally, the researchers ran the predictors over new samples, and compared the results of the predictors.

According to the researchers, the results of the study indicate that “a perfect age predictor can in principle be developed based on DNA methylation data.” The researchers found that larger sample sizes lead to a more accurate prediction of age. This seems to indicate that near-perfect epigenetic clocks can be built based on very large data sets.

The difference between the chronological age and the biological age measured by the Zhang clock seems to be associated with an increased risk of age-related diseases and death. That is also the case for the Horvath, Hannum, and Levine aging clocks. However, the existing approaches have limitations. And the researchers caution against a strict interpretation of estimates from epigenetic clocks as an indicator of mortality or lifespan.