CheekAge, an Epigenetic Clock Derived from Buccal Swab Data
The most widely used epigenetic clocks are built on DNA methylation data obtained from immune cells in blood samples. The research of recent years has indicated that different types of immune cell exhibit quite different characteristics of epigenetic aging, leading to some ongoing debate as to how best to interpret this data. There are other easily obtained sources of cells that lack this issue, however, such as a buccal swab of the interior of the cheek. Here, researchers discuss the ongoing development of CheekAge, a clock built on DNA methylation data obtained from a large buccal swab data set.
While earlier first-generation epigenetic aging clocks were trained to estimate chronological age as accurately as possible, more recent next-generation clocks incorporate DNA methylation information more pertinent to health, lifestyle, and/or outcomes. Recently, we produced a non-invasive next-generation epigenetic clock trained using DNA methylation data from more than 8,000 diverse adult buccal samples. While this clock correlated with various health, lifestyle, and disease factors, we did not assess its ability to capture mortality. To address this gap, we applied CheekAge to the longitudinal Lothian Birth Cohorts of 1921 and 1936.
To our knowledge, this is the first study to demonstrate that an aging biomarker optimized for buccal tissue can be applied to blood for mortality prediction. Our findings build on previous work from more than a decade ago, which found that buccal methylation data was highly informative for a variety of phenotypes and diseases. The magnitude of the hazard ratio for mortality prediction outcompetes all first-generation clocks tested and compares favorably to the next-generation blood-trained clock DNAm PhenoAge. These data suggest that adult buccal tissue, which is relatively painless and easy to collect in a variety of settings, may represent a rich source of aging biomarkers.