Epigenetic clocks reveal distinct biological aging pathways

A study led by the USC Leonard Davis School of Gerontology has revealed that different epigenetic clocks measure distinct biological processes during aging. By analyzing blood samples from 3,227 participants in the US Health and Retirement Study, researchers compared five widely used epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE—with gene expression patterns.

The findings, published in npj Aging, show that these mathematical models, which track DNA methylation, do not all capture the same biological signals. Some clocks are more closely linked to metabolism and cell growth, while others are more closely associated with immune system activity and inflammation.

Lead author Thalida Em Arpawong noted that aging involves complex cellular changes beyond chronological age. The researchers also developed new transcriptomic aging gene scores that complement existing epigenetic clocks, potentially offering stronger predictive power for age-related diseases and mortality.