Research explores DNA methylation clock accuracy across tissues

A new research paper was published in Aging (Aging-US) on January 3, 2025, in Volume 17, Issue 1, titled “Characterization of DNA methylation clock algorithms applied to diverse tissue types.”

Researchers Mark Richardson, Courtney Brandt, Niyati Jain, James L. Li, Kathryn Demanelis, Farzana Jasmine, Muhammad G. Kibriya, Lin Tong, and Brandon L. Pierce from the University of Chicago and University of Pittsburgh, studied how biological aging is measured using DNA. Their study found that while commonly used “DNA methylation clocks” work well for blood samples, they may be less reliable for other tissues like the lungs, colon, and kidneys.

DNA methylation clocks are widely used in forensic science, epigenetics and longevity research to estimate a person’s biological age based on chemical changes in DNA. These epigenetic clocks help scientists predict age-related diseases and assess how lifestyle factors, such as smoking, impact aging. Most were originally developed using blood samples, and their effectiveness in other tissues remains unclear. This study tested eight different DNA methylation clocks across nine human tissue types, including the lungs, prostate, ovaries, skeletal muscle, and kidneys. The researchers analyzed data from 973 tissue samples collected through the Genotype-Tissue Expression (GTEx) project.

Their analysis revealed significant differences in biological age estimates across tissues. While blood samples provided the most reliable results, other tissues showed noticeable variations. For example, testis and ovary tissues appeared younger than expected, while lung and colon tissues appeared older. 

“These differences across tissue types were most apparent for clocks trained using DNAm from blood only (e.g., Hannum), but also present for clocks trained on multiple tissue types (e.g., Horvath, a clock designed for pan-tissue age prediction.” 

These findings suggest that aging may not occur at the same rate in every organ, and that standard DNA methylation clocks may not always give accurate biological age estimates outside of blood samples. The authors suggest that new, organ-specific epigenetic clocks may be needed to improve biological age prediction. Creating tissue-specific aging clocks could also improve medical diagnostics, age-related disease prevention, and health monitoring.

The researchers emphasize that larger studies with more tissue-specific DNA methylation data are needed to refine these aging clocks. By improving these tools, scientists can better understand how aging affects different organs and develop more reliable methods for measuring biological age. These advancements could lead to better predictions of age-related diseases and new strategies for healthy aging.