USC research on epigenetic aging clocks

Researchers at the USC Leonard Davis School of Gerontology have conducted studies into the biological mechanisms of epigenetic clocks, which measure biological age through DNA methylation.

Initial findings highlighted significant variability in what the five most widely used epigenetic clocks actually measure. To address this, the research team developed new gene-expression based clocks designed to complement existing tools, demonstrating stronger predictive power regarding mortality and age-related diseases.

A study published in npj Aging, involving the analysis of blood samples from 3,227 participants in the US Health and Retirement Study, confirmed that different epigenetic clocks are associated with distinct biological processes. By comparing five widely used models—Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE—with gene expression patterns, researchers found that these mathematical models do not all capture the same biological signals.

While the clocks share commonalities in reflecting changes to metabolism and intercellular communication, some models correlate more closely with cellular growth and energy utilization, while others are tied to immune activity and inflammation. Lead author Thalida Em Arpawong noted that aging involves complex cellular changes beyond chronological age. To enhance predictive capabilities, the team developed new transcriptomic aging gene scores to complement existing epigenetic clocks, potentially offering stronger foresight regarding mortality and age-related diseases.