A forensic examiner arrives at a crime scene and lifts fingerprints. Epigenetic clocks work the same way: from chemical marks on DNA they determine how much a cell has aged. A tumor leaves its own "fingerprints," and almost always they point to decrepitude.
The researchers took 5528 samples from the TCGA database, which holds DNA methylation data for eight cancer types. For each sample they calculated biological age using seven different clocks. Age acceleration is the difference between predicted age and chronological age. In 44 of 56 combinations, tumors had higher acceleration than neighboring healthy tissue.
Then the scientists went deeper. They tested each CpG site (a stretch of DNA where methylation regulates genes) from the clocks for its ability to tell tumor from normal. Many sites differed strongly, and more often than not there were more marks than needed. Some sites, for instance those linked to the DDR1 and TBX5 genes, were altered across all tissues at once.
The examiner lifted the fingerprints, compared them with the database and named the age. Now doctors have a chance to do the same from a drop of blood or a sliver of tissue. What remains is to test these marks on independent data and figure out why the uterus refuses to age along with the tumor.
The Horvath clock, created in 2013, uses just 353 CpG sites, yet it works in almost all human tissues, including brain, liver, and lungs.
In the series "Altered Carbon," biological age and body condition can be changed, and in reality epigenetic clocks allow us to estimate how much cells are "older" than their passport age, which vaguely resembles the idea of biological monitoring from science fiction.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.